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FDA approves new treatment for hereditary transthyretin-mediated amyloidosis
, the second treatment approved in 2 months for the rare genetic disorder.
Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).
The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.
The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”
A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.
Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 109/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).
Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.
, the second treatment approved in 2 months for the rare genetic disorder.
Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).
The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.
The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”
A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.
Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 109/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).
Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.
, the second treatment approved in 2 months for the rare genetic disorder.
Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).
The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.
The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”
A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.
Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 109/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).
Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.
FDA expands approval of 9-valent HPV vaccine
The , men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.
The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.
The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.
“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.
Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.
The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.
Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.
The , men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.
The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.
The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.
“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.
Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.
The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.
Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.
The , men and women aged 27-45 years, the Food and Drug Administration announced on Oct. 5.
The vaccine (Gardasil 9) was previously approved for those aged 9-26 years.
The approval “represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement announcing the approval.
“The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing,” he added.
Gardasil 9, approved in 2014, covers the four HPV types included in the original Gardasil vaccine approved in 2006, plus five additional HPV types.
The approval is based on the results of a study and follow-up of about 3,200 women aged 27-45 years, followed for an average of 3.5 years, which found that the vaccine was 88% percent effective “in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine,” according to the FDA. The vaccine’s effectiveness in men in this age group is “inferred” from these results and from data on Gardasil in men aged 16-26 years, as well as “immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months,” the FDA statement noted.
Based on safety data in about 13,000 men and women, injection-site pain, swelling, redness, and headaches are the most common adverse reactions associated with Gardasil 9, the statement said. Gardasil 9 is manufactured by Merck.
FDA expands CoolSculpting indication to submandibular area
FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.
Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.
The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m2 when treating the submental and submandibular areas.
FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.
Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.
The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m2 when treating the submental and submandibular areas.
FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.
Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.
The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m2 when treating the submental and submandibular areas.
FDA approves emicizumab for hemophilia A without inhibitors
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.
FDA approves omadacycline for pneumonia and skin infections
The, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.
The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.
Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.
Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.
Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline
The, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.
The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.
Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.
Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.
Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline
The, for treating community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults, the manufacturer, Paratek, announced in a press release.
The company expects that omadacycline will be available in the first quarter of 2019. Administered once-daily in either oral or IV formulations, the antibiotic was effective and well tolerated across multiple trials, which altogether included almost 2,000 patients, according to Paratek. As part of the approval, the company has agreed to conduct postmarketing studies, specifically, more studies in CABP and in pediatric populations. “To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nuzyra and other antibacterial drugs, Nuzyra should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria,” according to a statement in the indications section of the prescribing information.
Omadacycline is contraindicated for patients with a known hypersensitivity to the drug or any members of the tetracycline class of antibacterial drugs; hypersensitivity reactions have been observed, so use should be discontinued if one is suspected. Use of this drug during later stages of pregnancy can lead to irreversible discoloration of the infant’s teeth and inhibition of bone growth; it should also not be used during breastfeeding.
Because omadacycline is structurally similar to tetracycline class drugs, some adverse reactions to those drugs may be seen with this one, such as photosensitivity, pseudotumor cerebri, and antianabolic action. Adverse reactions known to have an association with omadacycline include nausea, vomiting, hypertension, insomnia, diarrhea, constipation, and increases of alanine aminotransferase, aspartate aminotransferase, and/or gamma-glutamyl transferase.
Drug interactions may occur with anticoagulants, so dosage of those drugs may need to be reduced while treating with omadacycline. Antacids also are believed to have a drug interaction – specifically, impairing absorption of omadacycline
FDA approves Seysara for treatment of moderate to severe acne
vulgaris for people aged 9 years and older, according to a press release from Paratek, the drug’s manufacturer.
FDA approval is based on results from two phase 3 clinical trials (NCT02320149 and NCT02322866), in which patients received either sarecycline at 1.5 mg/kg per day or placebo for 12 weeks. Patients who received sarecycline were significantly more likely to reach the primary endpoint of improved acne severity based on absolute change in facial lesion counts and percentage of participants with Investigator Global Assessment success.
Common adverse events reported in the sarecycline group were nausea (3.2%), nasopharyngitis (2.8%), and headache (2.8%). The discontinuation rate due to adverse events among sarecycline-treated patients in both studies combined was 1.4%.
Sarecycline is an oral, narrow spectrum tetracycline-derived antibiotic with anti-inflammatory properties, and is approved for once-daily use, according to Paratek. Seysara will be marketed in the United States by Almirall SA.
vulgaris for people aged 9 years and older, according to a press release from Paratek, the drug’s manufacturer.
FDA approval is based on results from two phase 3 clinical trials (NCT02320149 and NCT02322866), in which patients received either sarecycline at 1.5 mg/kg per day or placebo for 12 weeks. Patients who received sarecycline were significantly more likely to reach the primary endpoint of improved acne severity based on absolute change in facial lesion counts and percentage of participants with Investigator Global Assessment success.
Common adverse events reported in the sarecycline group were nausea (3.2%), nasopharyngitis (2.8%), and headache (2.8%). The discontinuation rate due to adverse events among sarecycline-treated patients in both studies combined was 1.4%.
Sarecycline is an oral, narrow spectrum tetracycline-derived antibiotic with anti-inflammatory properties, and is approved for once-daily use, according to Paratek. Seysara will be marketed in the United States by Almirall SA.
vulgaris for people aged 9 years and older, according to a press release from Paratek, the drug’s manufacturer.
FDA approval is based on results from two phase 3 clinical trials (NCT02320149 and NCT02322866), in which patients received either sarecycline at 1.5 mg/kg per day or placebo for 12 weeks. Patients who received sarecycline were significantly more likely to reach the primary endpoint of improved acne severity based on absolute change in facial lesion counts and percentage of participants with Investigator Global Assessment success.
Common adverse events reported in the sarecycline group were nausea (3.2%), nasopharyngitis (2.8%), and headache (2.8%). The discontinuation rate due to adverse events among sarecycline-treated patients in both studies combined was 1.4%.
Sarecycline is an oral, narrow spectrum tetracycline-derived antibiotic with anti-inflammatory properties, and is approved for once-daily use, according to Paratek. Seysara will be marketed in the United States by Almirall SA.
FDA lifts partial hold on tazemetostat trials
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
The U.S. Food and Drug Administration has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas, according to a press release from the drug’s developer Epizyme.
The patient had been on study for approximately 15 months and had achieved a confirmed partial response. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.
“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” Robert Bazemore, president and chief executive officer of Epizyme, said in a webcast on Sept. 24.
Epizyme assessed the risk of secondary malignancies, including T-LBL, as well as the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials. A panel of external scientific and medical experts who reviewed the findings concluded that T-LBL risks appear to be confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.
“The team at Epizyme has worked diligently in collaboration with external experts and the FDA over the past several months,” Mr. Bazemore said.
The company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials. However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies. Mr. Bazemore said Epizyme hopes to submit a New Drug Application for tazemetostat in the treatment of epithelioid sarcoma.
Tazemetostat is under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid-tumor malignancies. The drug is also being studied as part of combination therapy for non–small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).
In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.
Epizyme is now working to resolve partial clinical holds placed on tazemetostat in France and Germany in order to resume trial enrollment in those countries.
FDA authorizes ClonoSEQ to detect MRD in ALL, myeloma
, the U.S. Food and Drug Administration announced. Marketing authorization of the ClonoSEQ assay was granted to Adaptive Biotechnologies.
The ClonoSEQ assay is an in vitro diagnostic test that uses multiplex polymerase chain reaction and next-generation sequencing to identify and quantify certain gene sequences in DNA extracted from the bone marrow from patients with ALL or multiple myeloma. This is a single-site assay collected by the patient’s provider and sent to Adaptive Biotechnologies for evaluation.
The ClonoSEQ assay is capable of detecting minimal residual disease at levels below 1 in 1 million cells. Currently, providers test for MRD using flow cytometry assays or polymerase chain reaction–based assays. Those methods are usually capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells.
“Determining whether a patient has residual cancer cells remaining after treatment provides information on how well a patient has responded to therapy and how long remission may last. Having a highly sensitive test available to measure minimal residual disease in ALL or multiple myeloma patients can help providers manage their patients’ care,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the accuracy, reliability, and effectiveness of tests intended to be used as an aid to measure MRD to assess the change in burden of disease during and after treatment. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests, the agency said in the release. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a previously approved device.
“The FDA is applying novel regulatory approaches to make sure that these rapidly evolving [next-generation sequencing] tests are accurate and reliable. At the same time, we’re seeing more and more laboratory-developed tests seek marketing authorization from the FDA,” he said, adding that the agency has put forward a plan to modernize the regulatory framework for all in vitro clinical tests.
The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from three previously conducted clinical studies including 273 patients with ALL, an ongoing study of 323 patients with multiple myeloma, and a study of 706 patients with multiple myeloma, according to the FDA release.
For patients with ALL, the ClonoSEQ assay was used to assess MRD at various disease burden thresholds to show that the MRD level correlated with event-free survival – the length of time, after treatment, that the patient remains free of certain complications or events. Patients whose ClonoSEQ assay result was MRD negative had longer event-free survival, while patients with higher MRD assay results had lower event-free survival. Similar patterns of results were seen for progression-free and disease-free survival in patients with multiple myeloma.
, the U.S. Food and Drug Administration announced. Marketing authorization of the ClonoSEQ assay was granted to Adaptive Biotechnologies.
The ClonoSEQ assay is an in vitro diagnostic test that uses multiplex polymerase chain reaction and next-generation sequencing to identify and quantify certain gene sequences in DNA extracted from the bone marrow from patients with ALL or multiple myeloma. This is a single-site assay collected by the patient’s provider and sent to Adaptive Biotechnologies for evaluation.
The ClonoSEQ assay is capable of detecting minimal residual disease at levels below 1 in 1 million cells. Currently, providers test for MRD using flow cytometry assays or polymerase chain reaction–based assays. Those methods are usually capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells.
“Determining whether a patient has residual cancer cells remaining after treatment provides information on how well a patient has responded to therapy and how long remission may last. Having a highly sensitive test available to measure minimal residual disease in ALL or multiple myeloma patients can help providers manage their patients’ care,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the accuracy, reliability, and effectiveness of tests intended to be used as an aid to measure MRD to assess the change in burden of disease during and after treatment. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests, the agency said in the release. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a previously approved device.
“The FDA is applying novel regulatory approaches to make sure that these rapidly evolving [next-generation sequencing] tests are accurate and reliable. At the same time, we’re seeing more and more laboratory-developed tests seek marketing authorization from the FDA,” he said, adding that the agency has put forward a plan to modernize the regulatory framework for all in vitro clinical tests.
The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from three previously conducted clinical studies including 273 patients with ALL, an ongoing study of 323 patients with multiple myeloma, and a study of 706 patients with multiple myeloma, according to the FDA release.
For patients with ALL, the ClonoSEQ assay was used to assess MRD at various disease burden thresholds to show that the MRD level correlated with event-free survival – the length of time, after treatment, that the patient remains free of certain complications or events. Patients whose ClonoSEQ assay result was MRD negative had longer event-free survival, while patients with higher MRD assay results had lower event-free survival. Similar patterns of results were seen for progression-free and disease-free survival in patients with multiple myeloma.
, the U.S. Food and Drug Administration announced. Marketing authorization of the ClonoSEQ assay was granted to Adaptive Biotechnologies.
The ClonoSEQ assay is an in vitro diagnostic test that uses multiplex polymerase chain reaction and next-generation sequencing to identify and quantify certain gene sequences in DNA extracted from the bone marrow from patients with ALL or multiple myeloma. This is a single-site assay collected by the patient’s provider and sent to Adaptive Biotechnologies for evaluation.
The ClonoSEQ assay is capable of detecting minimal residual disease at levels below 1 in 1 million cells. Currently, providers test for MRD using flow cytometry assays or polymerase chain reaction–based assays. Those methods are usually capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells.
“Determining whether a patient has residual cancer cells remaining after treatment provides information on how well a patient has responded to therapy and how long remission may last. Having a highly sensitive test available to measure minimal residual disease in ALL or multiple myeloma patients can help providers manage their patients’ care,” FDA Commissioner Scott Gottlieb, MD, said in a press release.
Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the accuracy, reliability, and effectiveness of tests intended to be used as an aid to measure MRD to assess the change in burden of disease during and after treatment. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests, the agency said in the release. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a previously approved device.
“The FDA is applying novel regulatory approaches to make sure that these rapidly evolving [next-generation sequencing] tests are accurate and reliable. At the same time, we’re seeing more and more laboratory-developed tests seek marketing authorization from the FDA,” he said, adding that the agency has put forward a plan to modernize the regulatory framework for all in vitro clinical tests.
The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from three previously conducted clinical studies including 273 patients with ALL, an ongoing study of 323 patients with multiple myeloma, and a study of 706 patients with multiple myeloma, according to the FDA release.
For patients with ALL, the ClonoSEQ assay was used to assess MRD at various disease burden thresholds to show that the MRD level correlated with event-free survival – the length of time, after treatment, that the patient remains free of certain complications or events. Patients whose ClonoSEQ assay result was MRD negative had longer event-free survival, while patients with higher MRD assay results had lower event-free survival. Similar patterns of results were seen for progression-free and disease-free survival in patients with multiple myeloma.
FDA approves oral dacomitinib for some metastatic NSCLC
The Food and Drug Administration has approved dacomitinib tablets (VIZIMPRO) for the first-line treatment of metastatic non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations.
The second-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) has a recommended dose of 45 mg once daily with or without food.
The approval is based on the randomized, active-controlled 452-patient ARCHER 1050 trial, in which the drug showed improvement in progression-free survival (PFS) versus gefitinib. The median PFS was 14.7 in the dacomitinib arm, compared with 9.2 months in the gefitinib arm (hazard ratio 0.59).
ARCHER 1050 trial participants had good performance status, no prior therapy for metastatic disease or recurrent disease and were disease-free for at least 12 months following systemic non-EGFR TKI-containing therapy. Dacomitinib and gefitinib were given once-daily at 45 mg and 250 mg oral doses, respectively, until disease progression or unacceptable toxicity.
No improvement was seen in overall response rate or overall survival with dacomitinib vs. gefitinib.
Of 394 patients who received dacomitinib, 27% experienced serious adverse reactions – most often diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus, according to the FDA. Those that most often lead to discontinuation were diarrhea and interstitial lung disease. Prescribing information for dacomitinib contains warnings and precautions for interstitial lung disease, diarrhea, and dermatologic adverse reactions.
The Food and Drug Administration has approved dacomitinib tablets (VIZIMPRO) for the first-line treatment of metastatic non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations.
The second-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) has a recommended dose of 45 mg once daily with or without food.
The approval is based on the randomized, active-controlled 452-patient ARCHER 1050 trial, in which the drug showed improvement in progression-free survival (PFS) versus gefitinib. The median PFS was 14.7 in the dacomitinib arm, compared with 9.2 months in the gefitinib arm (hazard ratio 0.59).
ARCHER 1050 trial participants had good performance status, no prior therapy for metastatic disease or recurrent disease and were disease-free for at least 12 months following systemic non-EGFR TKI-containing therapy. Dacomitinib and gefitinib were given once-daily at 45 mg and 250 mg oral doses, respectively, until disease progression or unacceptable toxicity.
No improvement was seen in overall response rate or overall survival with dacomitinib vs. gefitinib.
Of 394 patients who received dacomitinib, 27% experienced serious adverse reactions – most often diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus, according to the FDA. Those that most often lead to discontinuation were diarrhea and interstitial lung disease. Prescribing information for dacomitinib contains warnings and precautions for interstitial lung disease, diarrhea, and dermatologic adverse reactions.
The Food and Drug Administration has approved dacomitinib tablets (VIZIMPRO) for the first-line treatment of metastatic non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations.
The second-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) has a recommended dose of 45 mg once daily with or without food.
The approval is based on the randomized, active-controlled 452-patient ARCHER 1050 trial, in which the drug showed improvement in progression-free survival (PFS) versus gefitinib. The median PFS was 14.7 in the dacomitinib arm, compared with 9.2 months in the gefitinib arm (hazard ratio 0.59).
ARCHER 1050 trial participants had good performance status, no prior therapy for metastatic disease or recurrent disease and were disease-free for at least 12 months following systemic non-EGFR TKI-containing therapy. Dacomitinib and gefitinib were given once-daily at 45 mg and 250 mg oral doses, respectively, until disease progression or unacceptable toxicity.
No improvement was seen in overall response rate or overall survival with dacomitinib vs. gefitinib.
Of 394 patients who received dacomitinib, 27% experienced serious adverse reactions – most often diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, decreased weight, alopecia, cough, and pruritus, according to the FDA. Those that most often lead to discontinuation were diarrhea and interstitial lung disease. Prescribing information for dacomitinib contains warnings and precautions for interstitial lung disease, diarrhea, and dermatologic adverse reactions.
Emgality approved for migraine prevention in adults
The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.
FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.
In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.
In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.
The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.
Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.
The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.
The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.
FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.
In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.
In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.
The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.
Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.
The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.
The Food and Drug Administration has approved galcanezumab-gnlm (Emgality) for the preventive treatment of migraine in adults, according to an announcement from Eli Lilly, the drug’s manufacturer.
FDA approval is based on results of three different phase 3 clinical trials, EVOLVE-1, EVOLVE-2, and REGAIN. EVOLVE-1 and EVOLVE-2 were 6-month, double-blind, placebo-controlled studies that included adults with episodic migraine (4-14 headache days per month). REGAIN was a 3-month, double-blind, placebo-controlled study of adults with chronic migraine (at least 15 headache days per month). The primary endpoint of all trials was mean change from baseline in the number of monthly headache days.
In all trials, patients received either placebo, 120 mg galcanezumab-gnlm after an initial loading dose of 240 mg, or 240 mg galcanezumab-gnlm. In EVOLVE-1 and EVOLVE-2, people who received galcanezumab-gnlm had significantly fewer headache days per month than with placebo, and those who received galcanezumab-gnlm were also more likely to achieve a 50%, 75%, and 100% reduction in headache days.
In REGAIN, patients who received galcanezumab-gnlm experienced fewer headache days than those who received placebo, and were also more likely to achieve a 50% reduction in headache days. There was no difference between groups in likelihood of achieving a 75% or 100% reduction.
The recommended dosage, according to the label, is a monthly, 120-mg subcutaneous injection, with an initial loading dose of 240 mg. The most common adverse event associated with galcanezumab-gnlm was injection site reaction.
Galcanezumab-gnlm, a calcitonin gene–related peptide antagonist, is also under final review by the European Commission for approval in Europe.
The U.S. list price of galcanezumab-gnlm is $575 once-monthly, or $6,900 annually, and patients with commercial insurance are candidates to receive it free for up to 12 months as part of Lilly’s patient support program (subject to specific terms and conditions), according to the announcement.