FDA/CDC

The Food and Drug Administration has approved a new formulation of metoclopramide for relief of symptoms of diabetic gastroparesis in adults.

The product, called Gimoti (Evoke Pharma) delivers metoclopramide through nasal administration, offering an advantage over oral administration, which can be impeded because of slowed stomach emptying, the company said in an announcement of the approval. The delivery system provides 15 mg metoclopramide in each 70-mcL spray, which can be taken 30 minutes before each meal and at bedtime for 2-8 weeks, depending on symptomatic response, according to Gimoti’s prescribing information.

Metoclopramide, a dopamine-2 antagonist, has been available for 4 decades in oral and injection formulations. It carries a risk of developing tardive dyskinesia – a serious, often-irreversible movement disorder – that increases with duration of treatment. Therefore, use of the drug should not exceed 12 weeks. Other contraindications include a history of tardive dyskinesia, when stimulation of GI motility might be dangerous, pheochromocytoma and catecholamine-releasing paragangliomas, and epilepsy.

Henry Parkman, MD, who was involved with clinical trials leading to the approval, explained in the Evoke statement that “patients with gastroparesis suffer from characteristic symptoms such as nausea, abdominal pain, bloating, early satiety, as well as vomiting which can be severe and debilitating. These patients often have erratic absorption of orally administered drugs because of delayed gastric emptying.

“Unlike oral medications, Gimoti is administered nasally, bypassing the diseased GI track, allowing the drug to enter the bloodstream directly and therefore may provide predictable delivery of the therapy,” adds Dr. Parkman, chair and director of the Gastroenterology Motility Laboratory at Temple University, Philadelphia.

Gimoti will be available commercially in the fourth quarter of this year, according to Evoke.

chackett@mdedge.com

The Food and Drug Administration has approved a new formulation of metoclopramide for relief of symptoms of diabetic gastroparesis in adults.

The product, called Gimoti (Evoke Pharma) delivers metoclopramide through nasal administration, offering an advantage over oral administration, which can be impeded because of slowed stomach emptying, the company said in an announcement of the approval. The delivery system provides 15 mg metoclopramide in each 70-mcL spray, which can be taken 30 minutes before each meal and at bedtime for 2-8 weeks, depending on symptomatic response, according to Gimoti’s prescribing information.

Metoclopramide, a dopamine-2 antagonist, has been available for 4 decades in oral and injection formulations. It carries a risk of developing tardive dyskinesia – a serious, often-irreversible movement disorder – that increases with duration of treatment. Therefore, use of the drug should not exceed 12 weeks. Other contraindications include a history of tardive dyskinesia, when stimulation of GI motility might be dangerous, pheochromocytoma and catecholamine-releasing paragangliomas, and epilepsy.

Henry Parkman, MD, who was involved with clinical trials leading to the approval, explained in the Evoke statement that “patients with gastroparesis suffer from characteristic symptoms such as nausea, abdominal pain, bloating, early satiety, as well as vomiting which can be severe and debilitating. These patients often have erratic absorption of orally administered drugs because of delayed gastric emptying.

“Unlike oral medications, Gimoti is administered nasally, bypassing the diseased GI track, allowing the drug to enter the bloodstream directly and therefore may provide predictable delivery of the therapy,” adds Dr. Parkman, chair and director of the Gastroenterology Motility Laboratory at Temple University, Philadelphia.

Gimoti will be available commercially in the fourth quarter of this year, according to Evoke.

chackett@mdedge.com

The Food and Drug Administration has approved a new formulation of metoclopramide for relief of symptoms of diabetic gastroparesis in adults.

The product, called Gimoti (Evoke Pharma) delivers metoclopramide through nasal administration, offering an advantage over oral administration, which can be impeded because of slowed stomach emptying, the company said in an announcement of the approval. The delivery system provides 15 mg metoclopramide in each 70-mcL spray, which can be taken 30 minutes before each meal and at bedtime for 2-8 weeks, depending on symptomatic response, according to Gimoti’s prescribing information.

Metoclopramide, a dopamine-2 antagonist, has been available for 4 decades in oral and injection formulations. It carries a risk of developing tardive dyskinesia – a serious, often-irreversible movement disorder – that increases with duration of treatment. Therefore, use of the drug should not exceed 12 weeks. Other contraindications include a history of tardive dyskinesia, when stimulation of GI motility might be dangerous, pheochromocytoma and catecholamine-releasing paragangliomas, and epilepsy.

Henry Parkman, MD, who was involved with clinical trials leading to the approval, explained in the Evoke statement that “patients with gastroparesis suffer from characteristic symptoms such as nausea, abdominal pain, bloating, early satiety, as well as vomiting which can be severe and debilitating. These patients often have erratic absorption of orally administered drugs because of delayed gastric emptying.

“Unlike oral medications, Gimoti is administered nasally, bypassing the diseased GI track, allowing the drug to enter the bloodstream directly and therefore may provide predictable delivery of the therapy,” adds Dr. Parkman, chair and director of the Gastroenterology Motility Laboratory at Temple University, Philadelphia.

Gimoti will be available commercially in the fourth quarter of this year, according to Evoke.

chackett@mdedge.com

The US Food and Drug Administration has approved rapid-acting insulin lispro-aabc injection 100 and 200 units/mL (Lyumjev, Eli Lilly) for the treatment of adults with type 1 and type 2 diabetes.

The product is a novel formulation of insulin lispro developed to speed absorption of insulin into the bloodstream. It will be available in two strengths: U-100 (100 units/mL) and U-200 (200 units/mL). The Lyumjev U-200 prefilled pen contains twice as much insulin per 1 mL as standard (U-100) insulin.

Approval was based on data from two phase 3 randomized, active-controlled, treat-to-target studies comparing lispro-aabc with insulin lispro injection 100 units/mL (Humalog, Lilly) in people with type 1 diabetes (PRONTO-T1D) and type 2 diabetes (PRONTO-T2D).

In both studies, noninferiority in A1c reduction was demonstrated when the two insulins were dosed at mealtime, but lispro-aabc showed superior blood glucose reduction at 1-hour and 2-hours post-meal compared with lispro.

Lyumjev is approved only in the United States for use as part of a multiple daily injection regimen, not for use in insulin pumps. Lilly intends to submit for this latter indication later in 2020.

Lyumjev will compete with Novo Nordisk’s fast-acting insulin aspart injection 100 units/mL (Fiasp).

Fiasp had a big head start: It was approved for use in adults in the United States in September 2017, for use in insulin pumps in October 2019, and for use in children with diabetes in January 2020.

However, in a poster presented at the American Diabetes Association 79th Scientific Sessions in 2019, lispro-aabb demonstrated faster insulin absorption than lispro, insulin aspart (Novolog/Novorapid, Novo Nordisk), or Fiasp.

Early half-maximal drug concentration was reached at 13 minutes with lispro-aabb, compared with 19 minutes with faster aspart and 25-27 minutes with the two conventional insulins (P < .05 for lispro-aabb vs other insulins).  

Insulin lispro-aabc was approved in the European Union and Japan in March 2020.

Lilly is currently working to make Lyumjev available to adults with diabetes in the United States as quickly as possible and says it will be included in the Lilly Insulin Value Program, allowing anyone with commercial insurance and those without insurance to fill their monthly prescription of Lyumjev for $35.

The list price of Lyumjev will be the same as the list price for Humalog, it adds.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved rapid-acting insulin lispro-aabc injection 100 and 200 units/mL (Lyumjev, Eli Lilly) for the treatment of adults with type 1 and type 2 diabetes.

The product is a novel formulation of insulin lispro developed to speed absorption of insulin into the bloodstream. It will be available in two strengths: U-100 (100 units/mL) and U-200 (200 units/mL). The Lyumjev U-200 prefilled pen contains twice as much insulin per 1 mL as standard (U-100) insulin.

Approval was based on data from two phase 3 randomized, active-controlled, treat-to-target studies comparing lispro-aabc with insulin lispro injection 100 units/mL (Humalog, Lilly) in people with type 1 diabetes (PRONTO-T1D) and type 2 diabetes (PRONTO-T2D).

In both studies, noninferiority in A1c reduction was demonstrated when the two insulins were dosed at mealtime, but lispro-aabc showed superior blood glucose reduction at 1-hour and 2-hours post-meal compared with lispro.

Lyumjev is approved only in the United States for use as part of a multiple daily injection regimen, not for use in insulin pumps. Lilly intends to submit for this latter indication later in 2020.

Lyumjev will compete with Novo Nordisk’s fast-acting insulin aspart injection 100 units/mL (Fiasp).

Fiasp had a big head start: It was approved for use in adults in the United States in September 2017, for use in insulin pumps in October 2019, and for use in children with diabetes in January 2020.

However, in a poster presented at the American Diabetes Association 79th Scientific Sessions in 2019, lispro-aabb demonstrated faster insulin absorption than lispro, insulin aspart (Novolog/Novorapid, Novo Nordisk), or Fiasp.

Early half-maximal drug concentration was reached at 13 minutes with lispro-aabb, compared with 19 minutes with faster aspart and 25-27 minutes with the two conventional insulins (P < .05 for lispro-aabb vs other insulins).  

Insulin lispro-aabc was approved in the European Union and Japan in March 2020.

Lilly is currently working to make Lyumjev available to adults with diabetes in the United States as quickly as possible and says it will be included in the Lilly Insulin Value Program, allowing anyone with commercial insurance and those without insurance to fill their monthly prescription of Lyumjev for $35.

The list price of Lyumjev will be the same as the list price for Humalog, it adds.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved rapid-acting insulin lispro-aabc injection 100 and 200 units/mL (Lyumjev, Eli Lilly) for the treatment of adults with type 1 and type 2 diabetes.

The product is a novel formulation of insulin lispro developed to speed absorption of insulin into the bloodstream. It will be available in two strengths: U-100 (100 units/mL) and U-200 (200 units/mL). The Lyumjev U-200 prefilled pen contains twice as much insulin per 1 mL as standard (U-100) insulin.

Approval was based on data from two phase 3 randomized, active-controlled, treat-to-target studies comparing lispro-aabc with insulin lispro injection 100 units/mL (Humalog, Lilly) in people with type 1 diabetes (PRONTO-T1D) and type 2 diabetes (PRONTO-T2D).

In both studies, noninferiority in A1c reduction was demonstrated when the two insulins were dosed at mealtime, but lispro-aabc showed superior blood glucose reduction at 1-hour and 2-hours post-meal compared with lispro.

Lyumjev is approved only in the United States for use as part of a multiple daily injection regimen, not for use in insulin pumps. Lilly intends to submit for this latter indication later in 2020.

Lyumjev will compete with Novo Nordisk’s fast-acting insulin aspart injection 100 units/mL (Fiasp).

Fiasp had a big head start: It was approved for use in adults in the United States in September 2017, for use in insulin pumps in October 2019, and for use in children with diabetes in January 2020.

However, in a poster presented at the American Diabetes Association 79th Scientific Sessions in 2019, lispro-aabb demonstrated faster insulin absorption than lispro, insulin aspart (Novolog/Novorapid, Novo Nordisk), or Fiasp.

Early half-maximal drug concentration was reached at 13 minutes with lispro-aabb, compared with 19 minutes with faster aspart and 25-27 minutes with the two conventional insulins (P < .05 for lispro-aabb vs other insulins).  

Insulin lispro-aabc was approved in the European Union and Japan in March 2020.

Lilly is currently working to make Lyumjev available to adults with diabetes in the United States as quickly as possible and says it will be included in the Lilly Insulin Value Program, allowing anyone with commercial insurance and those without insurance to fill their monthly prescription of Lyumjev for $35.

The list price of Lyumjev will be the same as the list price for Humalog, it adds.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval of the EZH2 inhibitor tazemetostat (Tazverik, Epizyme, Inc) for the treatment of relapsed or refractory follicular lymphoma in adult patients with tumors harboring an EZH2 mutation.

Eligible patients must have already received at least two prior systemic therapies and have tumors that are positive for an EZH2 mutation, as detected by an FDA-approved test. The FDA has also approved the cobas EZH2 Mutation Test (Roche Molecular Systems, Inc) as a companion diagnostic test for tazemetostat.

The new indication is also for adult patients with relapsed/refractory follicular lymphoma who have no other satisfactory alternative treatment options.

“In our view, there remains no clear standard of care in the relapsed and/or refractory [follicular lymphoma] population, as not all patients benefit from today’s available therapies,” said Shefali Agarwal, MD, chief medical officer of Epizyme, in a company press release. “Based on this label, physicians will have the ability to use their clinical discretion to prescribe tazemetostat for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory.”

This accelerated approval is based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials, the FDA notes.

Tazemetostat acts as an inhibitor of EZH2 methyltransferase. Earlier this year, the drug was approved for the treatment of metastatic or locally advanced epithelioid sarcoma in cases in which complete resection is not possible. It is the first drug with this mechanism of action and is the first to be indicated for epithelioid sarcoma.

Promising Efficacy in Phase 2 Trial

The new approval for use in follicular lymphoma was based on results from an open-label, single-arm, multicenter phase 2 clinical trial involving patients who had experienced disease progression after being treated with at least two prior systemic regimens. The cohort was divided into two treatment groups: One group consisted of 45 patients with EZH2-activating mutations, the other included 54 patients with wild-type EZH2.

All patients received tazemetostat at 800 mg administered orally twice a day. The primary efficacy outcome measures were overall response rate and duration of response, in accordance with International Working Group Non-Hodgkin Lymphoma criteria.

The median duration of follow-up was 22 months for patients with EZH2-activating mutations and 36 months for those with wild-type tumors.

Among the 45 patients with an EZH2-activating mutation, the median number of lines of prior systemic therapy was 2.0 (range, 1 – 11). In 49% of patients, disease was refractory to rituximab, and in 49%, it was refractory to the patient’s last therapy.

The overall response rate was 69%; 12% of patients achieved a complete response, and 57% achieved a partial response. The median duration of response was 10.9 months and ongoing.

In the cohort of 54 patients with wild-type EZH2, the median number previous therapies was 3.0 (range, 1 – 8); in 59% of patients, disease was refractory to rituximab, and in 41%, it was refractory to the patient’s last therapy.

The overall response rate to tazemetostat treatment was 34%; 4% of patients achieved a complete response, and 30% achieved a partial response. The median duration of response was 13 months.

Serious adverse reactions occurred in 30% of patients. The most common were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Eight patients (8%) discontinued treatment during the trial because of adverse events. There were no reported deaths. No black box warnings have been published, and there are no contraindications.

“The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma,” said John Leonard, MD, in a company press release. He is associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and New York–Presbyterian Hospital, New York, and an investigator in the ongoing phase 1b/3 confirmatory trial for tazemetostat.

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” he commented.

This article first appeared on Medscape.com.

The Food and Drug Administration has expanded the indications for canakinumab (Ilaris) to include all patients with active Still’s disease older than 2 years, adding adult-onset Still’s disease (AOSD) to a previous approval for juvenile-onset Still’s disease, also known as systemic juvenile idiopathic arthritis (sJIA), making it the first approved treatment for AOSD, according to an FDA announcement.

The approval comes under a Priority Review designation that used “comparable pharmacokinetic exposure and extrapolation of established efficacy of canakinumab in patients with sJIA, as well as the safety of canakinumab in patients with AOSD and other diseases,” the FDA said.

The results from a randomized, double-blind, placebo-controlled study of 36 patients with AOSD aged 22-70 years showed that the efficacy and safety data in AOSD were generally consistent with the results of a pooled analysis of sJIA patients, according to Novartis, which markets canakinumab.

AOSD and sJIA share certain similarities, such as fever, arthritis, rash, and elevated markers of inflammation, which has led to suspicion that they are part of a continuum rather than wholly distinct, according to the agency. In addition, the role of interleukin-1 is well established in both diseases and is blocked by canakinumab.

The most common side effects (occurring in greater than 10% of patients) in sJIA studies included infections, abdominal pain, and injection-site reactions. Serious infections (e.g., pneumonia, varicella, gastroenteritis, measles, sepsis, otitis media, sinusitis, adenovirus, lymph node abscess, pharyngitis) were observed in approximately 4%-5%, according to the full prescribing information.

Canakinumab is also approved for the periodic fever syndromes of cryopyrin-associated periodic syndromes in adults and children aged 4 years and older (including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome), tumor necrosis factor receptor associated periodic syndrome in adult and pediatric patients, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency in adult and pediatric patients, and familial Mediterranean fever in adult and pediatric patients.

cpalmer@mdedge.com

The Food and Drug Administration has expanded the indications for canakinumab (Ilaris) to include all patients with active Still’s disease older than 2 years, adding adult-onset Still’s disease (AOSD) to a previous approval for juvenile-onset Still’s disease, also known as systemic juvenile idiopathic arthritis (sJIA), making it the first approved treatment for AOSD, according to an FDA announcement.

The approval comes under a Priority Review designation that used “comparable pharmacokinetic exposure and extrapolation of established efficacy of canakinumab in patients with sJIA, as well as the safety of canakinumab in patients with AOSD and other diseases,” the FDA said.

The results from a randomized, double-blind, placebo-controlled study of 36 patients with AOSD aged 22-70 years showed that the efficacy and safety data in AOSD were generally consistent with the results of a pooled analysis of sJIA patients, according to Novartis, which markets canakinumab.

AOSD and sJIA share certain similarities, such as fever, arthritis, rash, and elevated markers of inflammation, which has led to suspicion that they are part of a continuum rather than wholly distinct, according to the agency. In addition, the role of interleukin-1 is well established in both diseases and is blocked by canakinumab.

The most common side effects (occurring in greater than 10% of patients) in sJIA studies included infections, abdominal pain, and injection-site reactions. Serious infections (e.g., pneumonia, varicella, gastroenteritis, measles, sepsis, otitis media, sinusitis, adenovirus, lymph node abscess, pharyngitis) were observed in approximately 4%-5%, according to the full prescribing information.

Canakinumab is also approved for the periodic fever syndromes of cryopyrin-associated periodic syndromes in adults and children aged 4 years and older (including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome), tumor necrosis factor receptor associated periodic syndrome in adult and pediatric patients, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency in adult and pediatric patients, and familial Mediterranean fever in adult and pediatric patients.

cpalmer@mdedge.com

The Food and Drug Administration has expanded the indications for canakinumab (Ilaris) to include all patients with active Still’s disease older than 2 years, adding adult-onset Still’s disease (AOSD) to a previous approval for juvenile-onset Still’s disease, also known as systemic juvenile idiopathic arthritis (sJIA), making it the first approved treatment for AOSD, according to an FDA announcement.

The approval comes under a Priority Review designation that used “comparable pharmacokinetic exposure and extrapolation of established efficacy of canakinumab in patients with sJIA, as well as the safety of canakinumab in patients with AOSD and other diseases,” the FDA said.

The results from a randomized, double-blind, placebo-controlled study of 36 patients with AOSD aged 22-70 years showed that the efficacy and safety data in AOSD were generally consistent with the results of a pooled analysis of sJIA patients, according to Novartis, which markets canakinumab.

AOSD and sJIA share certain similarities, such as fever, arthritis, rash, and elevated markers of inflammation, which has led to suspicion that they are part of a continuum rather than wholly distinct, according to the agency. In addition, the role of interleukin-1 is well established in both diseases and is blocked by canakinumab.

The most common side effects (occurring in greater than 10% of patients) in sJIA studies included infections, abdominal pain, and injection-site reactions. Serious infections (e.g., pneumonia, varicella, gastroenteritis, measles, sepsis, otitis media, sinusitis, adenovirus, lymph node abscess, pharyngitis) were observed in approximately 4%-5%, according to the full prescribing information.

Canakinumab is also approved for the periodic fever syndromes of cryopyrin-associated periodic syndromes in adults and children aged 4 years and older (including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome), tumor necrosis factor receptor associated periodic syndrome in adult and pediatric patients, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency in adult and pediatric patients, and familial Mediterranean fever in adult and pediatric patients.

cpalmer@mdedge.com

The Food and Drug Administration has approved secukinumab (Cosentyx) for the treatment of active nonradiographic axial spondyloarthritis (nr-axSpA), according to an announcement from the drug’s manufacturer, Novartis.

FDA approval was based on results of the 2-year PREVENT trial, a randomized, double-blind, placebo-controlled, phase 3 study in 555 adults with active nr-axSpA who received a loading dose of 150 mg secukinumab subcutaneously weekly for 4 weeks, then maintenance dosing with 150 mg secukinumab monthly; 150 mg secukinumab monthly with no loading dose; or placebo. Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index, had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor (TNF) inhibitor or had an inadequate response to no more than one TNF inhibitor. A total of 501 patients had not previously taken a biologic medication.

A significantly greater proportion of biologic-naive patients taking secukinumab in both active treatment arm met the trial’s primary endpoint of at least a 40% improvement in the Assessment of Spondyloarthritis International Society response criteria versus placebo after 52 weeks. Both loading and nonloading arms saw significant improvements in Ankylosing Spondylitis Quality of Life scores, compared with those in the placebo group.

The safety profile of secukinumab in PREVENT was shown to be consistent with previous clinical trials, with no new safety signals detected.

Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, also received European Medicines Agency approval for the treatment of nr-axSpA in April 2020. It is already approved by the FDA for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.

lfranki@mdedge.com

The Food and Drug Administration has approved secukinumab (Cosentyx) for the treatment of active nonradiographic axial spondyloarthritis (nr-axSpA), according to an announcement from the drug’s manufacturer, Novartis.

FDA approval was based on results of the 2-year PREVENT trial, a randomized, double-blind, placebo-controlled, phase 3 study in 555 adults with active nr-axSpA who received a loading dose of 150 mg secukinumab subcutaneously weekly for 4 weeks, then maintenance dosing with 150 mg secukinumab monthly; 150 mg secukinumab monthly with no loading dose; or placebo. Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index, had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor (TNF) inhibitor or had an inadequate response to no more than one TNF inhibitor. A total of 501 patients had not previously taken a biologic medication.

A significantly greater proportion of biologic-naive patients taking secukinumab in both active treatment arm met the trial’s primary endpoint of at least a 40% improvement in the Assessment of Spondyloarthritis International Society response criteria versus placebo after 52 weeks. Both loading and nonloading arms saw significant improvements in Ankylosing Spondylitis Quality of Life scores, compared with those in the placebo group.

The safety profile of secukinumab in PREVENT was shown to be consistent with previous clinical trials, with no new safety signals detected.

Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, also received European Medicines Agency approval for the treatment of nr-axSpA in April 2020. It is already approved by the FDA for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.

lfranki@mdedge.com

The Food and Drug Administration has approved secukinumab (Cosentyx) for the treatment of active nonradiographic axial spondyloarthritis (nr-axSpA), according to an announcement from the drug’s manufacturer, Novartis.

FDA approval was based on results of the 2-year PREVENT trial, a randomized, double-blind, placebo-controlled, phase 3 study in 555 adults with active nr-axSpA who received a loading dose of 150 mg secukinumab subcutaneously weekly for 4 weeks, then maintenance dosing with 150 mg secukinumab monthly; 150 mg secukinumab monthly with no loading dose; or placebo. Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index, had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor (TNF) inhibitor or had an inadequate response to no more than one TNF inhibitor. A total of 501 patients had not previously taken a biologic medication.

A significantly greater proportion of biologic-naive patients taking secukinumab in both active treatment arm met the trial’s primary endpoint of at least a 40% improvement in the Assessment of Spondyloarthritis International Society response criteria versus placebo after 52 weeks. Both loading and nonloading arms saw significant improvements in Ankylosing Spondylitis Quality of Life scores, compared with those in the placebo group.

The safety profile of secukinumab in PREVENT was shown to be consistent with previous clinical trials, with no new safety signals detected.

Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, also received European Medicines Agency approval for the treatment of nr-axSpA in April 2020. It is already approved by the FDA for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.

lfranki@mdedge.com

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

Patients with metastatic small-cell lung cancer (SCLC) whose disease has progressed after or during treatment with platinum-based chemotherapy now have a new option to try — lurbinectedin (Zepzelca, Jazz Pharma/PharmaMar).

The drug was granted accelerated approval by the US Food and Drug Administration (FDA) based on response data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the FDA notes.

“Small-cell lung cancer is a disease with limited treatment options,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. “While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.”

“Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” Jeff Petty, MD, oncology specialist, Wake Forest Baptist Health, Winston-Salem, North Carolina, commented in the company press release. This new drug “is an important and much-needed addition to the treatment landscape for relapsing SCLC,” he added.
 

Approval based on monotherapy trial

The approval is based on a monotherapy clinical trial in 105 patients, which was published in May in Lancet Oncology, with first author José Trigo, MD, from the Hospital Universitario Virgen de la Victoria in Malaga, Spain.  

These were adult patients with both platinum-sensitive and platinum-resistant SCLC who had disease progression after treatment with platinum-based chemotherapy. They were treated at 26 hospitals across six European countries and the US. All patients received lurbinectedin at 3.2 mg/m² by intravenous infusion over 1 hour. Median follow-up was 17.1 months.

Overall response by investigator assessment was seen in 37 (35.2%) of the 105 patients. The response was greater (at 45%) among the patients with platinum-sensitive disease and smaller (22.2%) among those with platinum-resistant disease.

Lurbinectedin demonstrated a median duration of response of 5.3 months as measured by investigator assessment.

In a post-hoc analysis, among the 37 patients who had an initial objective response, the median overall survival was just over 1 year (12.6 months). It was even longer among patients who had platinum-sensitive disease (15.8 months), although it was shorter in patients with resistant disease (10.9 months).

These data are “particularly encouraging,” comment the authors of an accompanying editorial, led by Oscar Arrieta, MD, from the Thoracic Oncology Unit at the Instituto Nacional de Cancerología in Mexico City, Mexico. These response rates “outperform all previous results achieved with topotecan and other less established treatment schemes including cyclophosphamide, doxorubicin, and vincristine, or platinum re-challenge, in this setting.”

“Lurbinectedin represents an innovative approach to conventional anti-cancer drugs, with an elegant mechanism of action based on the inhibition of transcription-dependent replication stress and genome instability of tumor cells,” the editorialists comment. “The drug binds to specific DNA triplets commonly found in transcription sites and triggers cellular apoptosis.”

“At present, the only evidence-based second-line treatment approved for SCLC is topotecan, a topoisomerase 1 inhibitor with moderate activity in patients with sensitive disease, although its effect is much less evident in patients with resistant SCLC,” they continue.

“Overall, the study by Trigo and colleagues presents novel data for a very challenging disease for which few treatment options exist, and the data on response and survival do seem to outperform data from historical controls,” Arrieta and colleagues write.

The editorialists also note that, in this trial, a few patients had received immunotherapy as part of their first-line treatment, and some of these patients (5 of 8 patients, 68%) had “an outstanding rate of durable response to lurbinectedin.” This raises the possibility of a synergistic effect between immunotherapy and lurbinectedin, as the combination seems to enhance immune memory and impair subsequent tumor growth, they add. Further trials will need to explore sequencing of therapy, they suggest.

A large phase 3 study known as ATLANTIS is currently underway.  

The most common grade 3-4 adverse events in the present trial were hematologic abnormalities: anemia (9% of patients), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

The study was funded by PharmaMar. Trigo and coauthors, and Arrieta and fellow editorialists, all report relationships with pharmaceutical companies, as detailed in the published articles.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the Gardasil-9 (Merck) vaccine to include prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58.

This new indication is approved under the FDA’s accelerated approval program and is based on the vaccine’s effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial, which is currently underway.

“At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades,” Alain Luxembourg, MD, director, clinical research, Merck Research Laboratories, said in a statement. “Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers.”

This new indication doesn’t affect the current recommendations that are already in place. In 2018, a supplemental application for Gardasil 9 was approved to include women and men aged 27 through 45 years for preventing a variety of cancers including cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck were not included.

The original Gardasil vaccine came on the market in 2006, with an indication to prevent certain cancers and diseases caused by HPV types 6, 11, 16, and 18. It is no longer distributed in the United States.

In 2014, the FDA approved Gardasil 9, which extends the vaccine coverage for the initial four HPV types as five additional types (31, 33, 45, 52, and 58), and its initial indication was for use in both men and women between the ages of 9 through 26 years.
 

Head and neck cancers surpass cervical cancer

More than 2 decades ago, researchers first found a connection between HPV and a subset of head and neck cancers (Curr Opin Oncol. 1999;11(3):191-199). The cancers associated with HPV also appeared to have a different biology and disease pattern, as well as a better prognosis, compared with those that were unrelated. HPV is now responsible for the majority of oropharyngeal squamous cell cancers diagnosed in the United States.

A study published last year found that oral HPV infections were occurring with significantly less frequency among sexually active female adolescents who had received the quadrivalent vaccine, as compared with those who were unvaccinated.

These findings provided evidence that HPV vaccination was associated with a reduced frequency of HPV infection in the oral cavity, suggesting that vaccination could decrease the future risk of HPV-associated head and neck cancers.

The omission of head and neck cancers from the initial list of indications for the vaccine is notable because, according to data from the Centers for Disease Control and Prevention (CDC), oropharyngeal cancers are now the most common malignancy caused by HPV, surpassing cervical cancer.
 

Who will benefit?

An estimated 14 million new HPV infections occur every year in the United States, according to the CDC, and about 80% of individuals who are sexually active have been exposed at some point during their lifetime. In most people, however, the virus will clear on its own without causing any illness or symptoms.

In a Medscape videoblog, Sandra Adamson Fryhofer, MD, MACP, FRCP, helped clarify the adult population most likely to benefit from the vaccine. She pointed out that the HPV vaccine doesn’t treat HPV-related disease or help clear infections, and there are currently no clinical antibody tests or titers that can predict immunity.

“Many adults aged 27-45 have already been exposed to HPV early in life,” she said. Those in a long-term mutually monogamous relationship are not likely to get a new HPV infection. Those with multiple prior sex partners are more likely to have already been exposed to vaccine serotypes. For them, the vaccine will be less effective.”

Fryhofer added that individuals who are now at risk for exposure to a new HPV infection from a new sex partner are the ones most likely to benefit from HPV vaccination.
 

Confirmation needed

The FDA’s accelerated approval is contingent on confirmatory data, and Merck opened a clinical trial this past February to evaluate the efficacy, immunogenicity, and safety of the 9-valent HPV vaccine in men 20 to 45 years of age. The phase 3 multicenter randomized trial will have an estimated enrollment of 6000 men.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the Gardasil-9 (Merck) vaccine to include prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58.

This new indication is approved under the FDA’s accelerated approval program and is based on the vaccine’s effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial, which is currently underway.

“At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades,” Alain Luxembourg, MD, director, clinical research, Merck Research Laboratories, said in a statement. “Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers.”

This new indication doesn’t affect the current recommendations that are already in place. In 2018, a supplemental application for Gardasil 9 was approved to include women and men aged 27 through 45 years for preventing a variety of cancers including cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck were not included.

The original Gardasil vaccine came on the market in 2006, with an indication to prevent certain cancers and diseases caused by HPV types 6, 11, 16, and 18. It is no longer distributed in the United States.

In 2014, the FDA approved Gardasil 9, which extends the vaccine coverage for the initial four HPV types as five additional types (31, 33, 45, 52, and 58), and its initial indication was for use in both men and women between the ages of 9 through 26 years.
 

Head and neck cancers surpass cervical cancer

More than 2 decades ago, researchers first found a connection between HPV and a subset of head and neck cancers (Curr Opin Oncol. 1999;11(3):191-199). The cancers associated with HPV also appeared to have a different biology and disease pattern, as well as a better prognosis, compared with those that were unrelated. HPV is now responsible for the majority of oropharyngeal squamous cell cancers diagnosed in the United States.

A study published last year found that oral HPV infections were occurring with significantly less frequency among sexually active female adolescents who had received the quadrivalent vaccine, as compared with those who were unvaccinated.

These findings provided evidence that HPV vaccination was associated with a reduced frequency of HPV infection in the oral cavity, suggesting that vaccination could decrease the future risk of HPV-associated head and neck cancers.

The omission of head and neck cancers from the initial list of indications for the vaccine is notable because, according to data from the Centers for Disease Control and Prevention (CDC), oropharyngeal cancers are now the most common malignancy caused by HPV, surpassing cervical cancer.
 

Who will benefit?

An estimated 14 million new HPV infections occur every year in the United States, according to the CDC, and about 80% of individuals who are sexually active have been exposed at some point during their lifetime. In most people, however, the virus will clear on its own without causing any illness or symptoms.

In a Medscape videoblog, Sandra Adamson Fryhofer, MD, MACP, FRCP, helped clarify the adult population most likely to benefit from the vaccine. She pointed out that the HPV vaccine doesn’t treat HPV-related disease or help clear infections, and there are currently no clinical antibody tests or titers that can predict immunity.

“Many adults aged 27-45 have already been exposed to HPV early in life,” she said. Those in a long-term mutually monogamous relationship are not likely to get a new HPV infection. Those with multiple prior sex partners are more likely to have already been exposed to vaccine serotypes. For them, the vaccine will be less effective.”

Fryhofer added that individuals who are now at risk for exposure to a new HPV infection from a new sex partner are the ones most likely to benefit from HPV vaccination.
 

Confirmation needed

The FDA’s accelerated approval is contingent on confirmatory data, and Merck opened a clinical trial this past February to evaluate the efficacy, immunogenicity, and safety of the 9-valent HPV vaccine in men 20 to 45 years of age. The phase 3 multicenter randomized trial will have an estimated enrollment of 6000 men.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the Gardasil-9 (Merck) vaccine to include prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58.

This new indication is approved under the FDA’s accelerated approval program and is based on the vaccine’s effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial, which is currently underway.

“At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades,” Alain Luxembourg, MD, director, clinical research, Merck Research Laboratories, said in a statement. “Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers.”

This new indication doesn’t affect the current recommendations that are already in place. In 2018, a supplemental application for Gardasil 9 was approved to include women and men aged 27 through 45 years for preventing a variety of cancers including cervical, vulvar, vaginal, and anal cancer as well as genital warts. But cancers of the head and neck were not included.

The original Gardasil vaccine came on the market in 2006, with an indication to prevent certain cancers and diseases caused by HPV types 6, 11, 16, and 18. It is no longer distributed in the United States.

In 2014, the FDA approved Gardasil 9, which extends the vaccine coverage for the initial four HPV types as five additional types (31, 33, 45, 52, and 58), and its initial indication was for use in both men and women between the ages of 9 through 26 years.
 

Head and neck cancers surpass cervical cancer

More than 2 decades ago, researchers first found a connection between HPV and a subset of head and neck cancers (Curr Opin Oncol. 1999;11(3):191-199). The cancers associated with HPV also appeared to have a different biology and disease pattern, as well as a better prognosis, compared with those that were unrelated. HPV is now responsible for the majority of oropharyngeal squamous cell cancers diagnosed in the United States.

A study published last year found that oral HPV infections were occurring with significantly less frequency among sexually active female adolescents who had received the quadrivalent vaccine, as compared with those who were unvaccinated.

These findings provided evidence that HPV vaccination was associated with a reduced frequency of HPV infection in the oral cavity, suggesting that vaccination could decrease the future risk of HPV-associated head and neck cancers.

The omission of head and neck cancers from the initial list of indications for the vaccine is notable because, according to data from the Centers for Disease Control and Prevention (CDC), oropharyngeal cancers are now the most common malignancy caused by HPV, surpassing cervical cancer.
 

Who will benefit?

An estimated 14 million new HPV infections occur every year in the United States, according to the CDC, and about 80% of individuals who are sexually active have been exposed at some point during their lifetime. In most people, however, the virus will clear on its own without causing any illness or symptoms.

In a Medscape videoblog, Sandra Adamson Fryhofer, MD, MACP, FRCP, helped clarify the adult population most likely to benefit from the vaccine. She pointed out that the HPV vaccine doesn’t treat HPV-related disease or help clear infections, and there are currently no clinical antibody tests or titers that can predict immunity.

“Many adults aged 27-45 have already been exposed to HPV early in life,” she said. Those in a long-term mutually monogamous relationship are not likely to get a new HPV infection. Those with multiple prior sex partners are more likely to have already been exposed to vaccine serotypes. For them, the vaccine will be less effective.”

Fryhofer added that individuals who are now at risk for exposure to a new HPV infection from a new sex partner are the ones most likely to benefit from HPV vaccination.
 

Confirmation needed

The FDA’s accelerated approval is contingent on confirmatory data, and Merck opened a clinical trial this past February to evaluate the efficacy, immunogenicity, and safety of the 9-valent HPV vaccine in men 20 to 45 years of age. The phase 3 multicenter randomized trial will have an estimated enrollment of 6000 men.

This article first appeared on Medscape.com.

Semglee, a long-acting human insulin analogue, has been approved for glycemic control in adults and children with type 1 diabetes and adults with type 2 diabetes, the Food and Drug Administration announced June 11.

“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.

Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.

The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.

The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.

Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.

“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.

rfranki@mdedge.com

Semglee, a long-acting human insulin analogue, has been approved for glycemic control in adults and children with type 1 diabetes and adults with type 2 diabetes, the Food and Drug Administration announced June 11.

“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.

Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.

The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.

The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.

Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.

“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.

rfranki@mdedge.com

Semglee, a long-acting human insulin analogue, has been approved for glycemic control in adults and children with type 1 diabetes and adults with type 2 diabetes, the Food and Drug Administration announced June 11.

“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.

Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.

The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.

The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.

Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.

“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.

rfranki@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

A version of this article originally appeared on Medscape.com.