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FDA approves ibrutinib with rituximab in Waldenström’s macroglobulinemia
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
Elotuzumab under review for relapsed/refractory myeloma
The Food and Drug Administration has granted .
Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.
The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.
The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.
The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The Food and Drug Administration has granted .
Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.
The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.
The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.
The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The Food and Drug Administration has granted .
Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.
The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.
The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.
The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Valsartan recalls: FDA, manufacturers issue advisories
This story updated Aug. 23 to include additional recall and release of new test. The FDA added an updated statement on their ongoing investigation on Aug. 30 and again on Oct. 24.
for recognizing the recalled products and prescribing replacement products.
The affected products containing the active ingredient valsartan were voluntarily recalled because of the detection of N-nitrosodimethylamine (NDMA), an impurity that is classified as a probable carcinogen. The presence of NDMA was unexpected and is thought to be related to changes in the manufacturing process, the FDA announced in a press release.
The voluntary recall affects all lots of nonexpired products that contain the ingredient valsartan supplied to companies by Zhejiang Huahai Pharmaceuticals, Linhai, China. This company has stopped distributing valsartan. The FDA is working with the affected manufacturers – Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals – to reduce or eliminate impure valsartan from future products. The voluntary recall also applies to Solco and Teva valsartan/hydrochlorothiazide (HCTZ) combination products.
On Aug. 23, the FDA announced that the recall was extended to all valsartan-containing products from Torrent Pharmaceuticals Limited.
The agency said its review is ongoing and includes investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them, and what measures can be taken to reduce or eliminate the impurity from future batches.
“Our drug shortages team is also working hard to ensure patients’ therapeutic needs are met in the United States with an adequate supply of unaffected medications,” FDA Commissioner Scott Gottlieb, MD, said.
Additionally, the FDA on Aug. 23 released a gas chromatography-mass spectrometry (GC/MS) headspace method that drug manufacturers and regulators can use to detect and quantify NDMA in valsartan and finished drug products.
In the interim, patients taking the recalled valsartan-containing medicines should continue taking their medicine until they have a replacement product, the statement said. To determine whether a specific product has been recalled, patients should be instructed to look at the drug name and company name on the label of their prescription bottle. If the information is not on the bottle, patients should contact the pharmacy that dispensed the medicine.
If a patient is taking one of the recalled medicines, they should follow the recall instructions provided by the specific company, according to the FDA.
Contact information for each manufacturer can be found at the following links:
Major Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613625.htm.
Solco Healthcare: www.fda.gov/Safety/Recalls/ucm613504.htm.
Teva Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613729.htm.
Torrent Pharmaceuticals Limited: https://www.fda.gov/Safety/Recalls/ucm617821.htm
This story updated Aug. 23 to include additional recall and release of new test. The FDA added an updated statement on their ongoing investigation on Aug. 30 and again on Oct. 24.
for recognizing the recalled products and prescribing replacement products.
The affected products containing the active ingredient valsartan were voluntarily recalled because of the detection of N-nitrosodimethylamine (NDMA), an impurity that is classified as a probable carcinogen. The presence of NDMA was unexpected and is thought to be related to changes in the manufacturing process, the FDA announced in a press release.
The voluntary recall affects all lots of nonexpired products that contain the ingredient valsartan supplied to companies by Zhejiang Huahai Pharmaceuticals, Linhai, China. This company has stopped distributing valsartan. The FDA is working with the affected manufacturers – Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals – to reduce or eliminate impure valsartan from future products. The voluntary recall also applies to Solco and Teva valsartan/hydrochlorothiazide (HCTZ) combination products.
On Aug. 23, the FDA announced that the recall was extended to all valsartan-containing products from Torrent Pharmaceuticals Limited.
The agency said its review is ongoing and includes investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them, and what measures can be taken to reduce or eliminate the impurity from future batches.
“Our drug shortages team is also working hard to ensure patients’ therapeutic needs are met in the United States with an adequate supply of unaffected medications,” FDA Commissioner Scott Gottlieb, MD, said.
Additionally, the FDA on Aug. 23 released a gas chromatography-mass spectrometry (GC/MS) headspace method that drug manufacturers and regulators can use to detect and quantify NDMA in valsartan and finished drug products.
In the interim, patients taking the recalled valsartan-containing medicines should continue taking their medicine until they have a replacement product, the statement said. To determine whether a specific product has been recalled, patients should be instructed to look at the drug name and company name on the label of their prescription bottle. If the information is not on the bottle, patients should contact the pharmacy that dispensed the medicine.
If a patient is taking one of the recalled medicines, they should follow the recall instructions provided by the specific company, according to the FDA.
Contact information for each manufacturer can be found at the following links:
Major Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613625.htm.
Solco Healthcare: www.fda.gov/Safety/Recalls/ucm613504.htm.
Teva Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613729.htm.
Torrent Pharmaceuticals Limited: https://www.fda.gov/Safety/Recalls/ucm617821.htm
This story updated Aug. 23 to include additional recall and release of new test. The FDA added an updated statement on their ongoing investigation on Aug. 30 and again on Oct. 24.
for recognizing the recalled products and prescribing replacement products.
The affected products containing the active ingredient valsartan were voluntarily recalled because of the detection of N-nitrosodimethylamine (NDMA), an impurity that is classified as a probable carcinogen. The presence of NDMA was unexpected and is thought to be related to changes in the manufacturing process, the FDA announced in a press release.
The voluntary recall affects all lots of nonexpired products that contain the ingredient valsartan supplied to companies by Zhejiang Huahai Pharmaceuticals, Linhai, China. This company has stopped distributing valsartan. The FDA is working with the affected manufacturers – Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals – to reduce or eliminate impure valsartan from future products. The voluntary recall also applies to Solco and Teva valsartan/hydrochlorothiazide (HCTZ) combination products.
On Aug. 23, the FDA announced that the recall was extended to all valsartan-containing products from Torrent Pharmaceuticals Limited.
The agency said its review is ongoing and includes investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them, and what measures can be taken to reduce or eliminate the impurity from future batches.
“Our drug shortages team is also working hard to ensure patients’ therapeutic needs are met in the United States with an adequate supply of unaffected medications,” FDA Commissioner Scott Gottlieb, MD, said.
Additionally, the FDA on Aug. 23 released a gas chromatography-mass spectrometry (GC/MS) headspace method that drug manufacturers and regulators can use to detect and quantify NDMA in valsartan and finished drug products.
In the interim, patients taking the recalled valsartan-containing medicines should continue taking their medicine until they have a replacement product, the statement said. To determine whether a specific product has been recalled, patients should be instructed to look at the drug name and company name on the label of their prescription bottle. If the information is not on the bottle, patients should contact the pharmacy that dispensed the medicine.
If a patient is taking one of the recalled medicines, they should follow the recall instructions provided by the specific company, according to the FDA.
Contact information for each manufacturer can be found at the following links:
Major Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613625.htm.
Solco Healthcare: www.fda.gov/Safety/Recalls/ucm613504.htm.
Teva Pharmaceuticals: www.fda.gov/Safety/Recalls/ucm613729.htm.
Torrent Pharmaceuticals Limited: https://www.fda.gov/Safety/Recalls/ucm617821.htm
FDA approves Diacomit for Dravet syndrome
The Food and Drug Administration has approved stiripentol (Diacomit) for the treatment of Dravet syndrome in patients aged 2 years and older who are taking clobazam.
Dravet syndrome is a rare form of epilepsy that presents within the first year as febrile seizures and then with other types of seizure later in life. Status epilepticus, a potentially life-threatening medical emergency, is a known risk. Also, developmental and interpersonal difficulties have been associated with this syndrome.
Because there are no clinical data for using stiripentol as monotherapy, it is indicated for use only in conjunction with clobazam. The recommended dosage for stiripentol is 50 mg/kg per day divided into either two or three doses, although the maximum recommended daily dose is 3,000 mg. It is available as either capsules or powder for oral solution, both of which come in either 250-mg or 500-mg forms.
Adverse reactions include somnolence, decreased appetite and weight, neutropenia and thrombocytopenia, tremor, nausea, and suicidal behavior and ideation. Because of the risk of neutropenia and thrombocytopenia, blood counts should be obtained via hematologic testing before starting stiripentol and again every 6 months. Also, as with most antiepileptic drugs, there is a risk of withdrawal symptoms, such as risk of increased seizure frequency and status epilepticus; as such, patients should not discontinue stiripentol without first consulting their health care professional.
Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved stiripentol (Diacomit) for the treatment of Dravet syndrome in patients aged 2 years and older who are taking clobazam.
Dravet syndrome is a rare form of epilepsy that presents within the first year as febrile seizures and then with other types of seizure later in life. Status epilepticus, a potentially life-threatening medical emergency, is a known risk. Also, developmental and interpersonal difficulties have been associated with this syndrome.
Because there are no clinical data for using stiripentol as monotherapy, it is indicated for use only in conjunction with clobazam. The recommended dosage for stiripentol is 50 mg/kg per day divided into either two or three doses, although the maximum recommended daily dose is 3,000 mg. It is available as either capsules or powder for oral solution, both of which come in either 250-mg or 500-mg forms.
Adverse reactions include somnolence, decreased appetite and weight, neutropenia and thrombocytopenia, tremor, nausea, and suicidal behavior and ideation. Because of the risk of neutropenia and thrombocytopenia, blood counts should be obtained via hematologic testing before starting stiripentol and again every 6 months. Also, as with most antiepileptic drugs, there is a risk of withdrawal symptoms, such as risk of increased seizure frequency and status epilepticus; as such, patients should not discontinue stiripentol without first consulting their health care professional.
Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved stiripentol (Diacomit) for the treatment of Dravet syndrome in patients aged 2 years and older who are taking clobazam.
Dravet syndrome is a rare form of epilepsy that presents within the first year as febrile seizures and then with other types of seizure later in life. Status epilepticus, a potentially life-threatening medical emergency, is a known risk. Also, developmental and interpersonal difficulties have been associated with this syndrome.
Because there are no clinical data for using stiripentol as monotherapy, it is indicated for use only in conjunction with clobazam. The recommended dosage for stiripentol is 50 mg/kg per day divided into either two or three doses, although the maximum recommended daily dose is 3,000 mg. It is available as either capsules or powder for oral solution, both of which come in either 250-mg or 500-mg forms.
Adverse reactions include somnolence, decreased appetite and weight, neutropenia and thrombocytopenia, tremor, nausea, and suicidal behavior and ideation. Because of the risk of neutropenia and thrombocytopenia, blood counts should be obtained via hematologic testing before starting stiripentol and again every 6 months. Also, as with most antiepileptic drugs, there is a risk of withdrawal symptoms, such as risk of increased seizure frequency and status epilepticus; as such, patients should not discontinue stiripentol without first consulting their health care professional.
Full prescribing information can be found on the FDA website.
Bertilimumab granted orphan drug status for bullous pemphigoid
The , according to an announcement issued by the company that is developing the treatment.
The company, Immune Pharmaceuticals, plans to launch a pivotal phase 2/3 study in 2019, the company said in an Aug. 20 press release. Two phase 2 studies of bertilimumab are currently underway, one in patients with bullous pemphigoid, and another in patients with ulcerative colitis. Bertilimumab is “a first-in-class, fully human monoclonal antibody that targets and lowers levels of eotaxin-1, a chemokine that plays a role in immune responses and attracts eosinophils to the site of inflammation,” the statement said.“By neutralizing eotaxin-1, bertilimumab may prevent the migration of eosinophils and other cells, thus helping to relieve associated inflammatory conditions.”
The FDA’s Orphan Drug Designation program grants orphan status to drugs and biologics, which are “defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug,” according to the agency.
The , according to an announcement issued by the company that is developing the treatment.
The company, Immune Pharmaceuticals, plans to launch a pivotal phase 2/3 study in 2019, the company said in an Aug. 20 press release. Two phase 2 studies of bertilimumab are currently underway, one in patients with bullous pemphigoid, and another in patients with ulcerative colitis. Bertilimumab is “a first-in-class, fully human monoclonal antibody that targets and lowers levels of eotaxin-1, a chemokine that plays a role in immune responses and attracts eosinophils to the site of inflammation,” the statement said.“By neutralizing eotaxin-1, bertilimumab may prevent the migration of eosinophils and other cells, thus helping to relieve associated inflammatory conditions.”
The FDA’s Orphan Drug Designation program grants orphan status to drugs and biologics, which are “defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug,” according to the agency.
The , according to an announcement issued by the company that is developing the treatment.
The company, Immune Pharmaceuticals, plans to launch a pivotal phase 2/3 study in 2019, the company said in an Aug. 20 press release. Two phase 2 studies of bertilimumab are currently underway, one in patients with bullous pemphigoid, and another in patients with ulcerative colitis. Bertilimumab is “a first-in-class, fully human monoclonal antibody that targets and lowers levels of eotaxin-1, a chemokine that plays a role in immune responses and attracts eosinophils to the site of inflammation,” the statement said.“By neutralizing eotaxin-1, bertilimumab may prevent the migration of eosinophils and other cells, thus helping to relieve associated inflammatory conditions.”
The FDA’s Orphan Drug Designation program grants orphan status to drugs and biologics, which are “defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug,” according to the agency.
FDA grants orphan designation to DHODH inhibitor for AML
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
FDA grants full approval to pembrolizumab for advanced NSCLC
(NSCLC), with no EGFR or ALK genomic tumor aberrations.
The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.
Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.
There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).
Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.
The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).
(NSCLC), with no EGFR or ALK genomic tumor aberrations.
The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.
Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.
There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).
Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.
The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).
(NSCLC), with no EGFR or ALK genomic tumor aberrations.
The checkpoint inhibitor was previously approved for patients with metastatic nonsquamous NSCLC in 2017, under the accelerated approval process, based on phase 2 results. Approval is now converted to a full approval, based on the results of the phase 3 Keynote-189 trial.
Patients in Keynote-189 who received pembrolizumab in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (hazard ratio, 0.49 [95% confidence interval, 0.38-0.64]; P less than .00001), according to the company press statement.
There was also a significant improvement in progression-free survival (PFS) with the pembrolizumab plus chemotherapy combination, compared with chemotherapy alone (HR, 0.52 [95% CI, 0.43-0.64]; P less than .00001).
Patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations were randomized to receive pembrolizumab 200 mg, cisplatin or carboplatin, and pemetrexed intravenously every 3 weeks for four cycles followed by pembrolizumab 200 mg for up to 24 months and pemetrexed every 3 weeks (n = 410); or cisplatin or carboplatin and pemetrexed intravenously every 3 weeks for four cycles followed by pemetrexed every 3 weeks (n = 206). Treatment continued until progression of disease or unacceptable toxicity.
The most common adverse reactions with pembrolizumab, resulting in discontinuation, were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions or laboratory abnormalities resulting in interruption of treatment were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%).
In the U.S., breastfeeding starts out strong, but drops off fast
More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.
The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.
Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.
The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.
“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”
The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.
The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.
Since the first report card in 2007, rates of exclusive breastfeeding at 3 and 6 months have increased. However, although rates for any breastfeeding at 6 and 12 months increased in 2015 from 2014 rates, there was no appreciable increase in exclusive breastfeeding at 3 and 6 months, the report noted. And about 17% of infants who were breastfed at birth still got some formula supplementation in the first 2 days of life.
Recognizing that breastfeeding support at the birth facility is a key driver of success, Healthy People 2020 tracks the proportion of live births in facilities that provided the recommended support. These “baby-friendly hospitals” receive a special designation from the WHO/UNICEF Baby-Friendly Hospital Initiative, and their numbers are increasing, the report noted. In 12 states, more than 40% of births occurred in such facilities, comprising more than 1 million infants in 2015 (26%), and far exceeding the HP2020 8% goal.
In a nation in which many new mothers must return to employment outside the home, breastfeeding support at work is crucial. Just 49% of employers provide breastfeeding facilities for these women, the report found. While this may seem less than optimal, it still exceeds the HP2020 goal of 38%.
“All sectors of society – family and friends, hospitals, health care offices/clinics, childcare facilities, community-based organizations, and workplaces – can play a role in improving the health of families by supporting breastfeeding,” the report said. “To reach their breastfeeding goals, mothers need continuity of care, which is achieved by consistent, collaborative, and high-quality breastfeeding services and support.”
SOURCE: CDC Breastfeeding Report Card
More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.
The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.
Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.
The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.
“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”
The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.
The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.
Since the first report card in 2007, rates of exclusive breastfeeding at 3 and 6 months have increased. However, although rates for any breastfeeding at 6 and 12 months increased in 2015 from 2014 rates, there was no appreciable increase in exclusive breastfeeding at 3 and 6 months, the report noted. And about 17% of infants who were breastfed at birth still got some formula supplementation in the first 2 days of life.
Recognizing that breastfeeding support at the birth facility is a key driver of success, Healthy People 2020 tracks the proportion of live births in facilities that provided the recommended support. These “baby-friendly hospitals” receive a special designation from the WHO/UNICEF Baby-Friendly Hospital Initiative, and their numbers are increasing, the report noted. In 12 states, more than 40% of births occurred in such facilities, comprising more than 1 million infants in 2015 (26%), and far exceeding the HP2020 8% goal.
In a nation in which many new mothers must return to employment outside the home, breastfeeding support at work is crucial. Just 49% of employers provide breastfeeding facilities for these women, the report found. While this may seem less than optimal, it still exceeds the HP2020 goal of 38%.
“All sectors of society – family and friends, hospitals, health care offices/clinics, childcare facilities, community-based organizations, and workplaces – can play a role in improving the health of families by supporting breastfeeding,” the report said. “To reach their breastfeeding goals, mothers need continuity of care, which is achieved by consistent, collaborative, and high-quality breastfeeding services and support.”
SOURCE: CDC Breastfeeding Report Card
More than half the infants born in the United States in 2015 (57.6%) were still breastfeeding at 6 months old – an improvement over 2014 survey results, and another step toward the 61% goal set forth in Healthy People 2020.
The CDC Breastfeeding Report Card for 2018 found that about 83% of infants born in 2015 started to breastfeed at birth. Further, five of eight Healthy People 2020 breastfeeding goals were met in 2015.
Yet, the numbers also paint a picture familiar to many clinicians and families: By 1 year, only 36% of infants were still breastfeeding, and just 25% of infants were exclusively breastfed through 6 months, as the American Academy of Pediatrics recommends. This puts the U.S. on the lower end of the global breastfeeding scale, with most countries reporting rates of 30% and higher, according to World Health Organization data. Globally, 41% of mothers breastfeed exclusively through 6 months, according to the latest UNICEF data.
The report concludes that U.S. mothers may not be getting the support they need from health care providers, family members, and employers to meet their breastfeeding goals.
“High breastfeeding initiation rates show that most mothers in the United States want to breastfeed and start out doing so,” the report states. “However, despite the recommendation to breastfeed exclusively for about the first 6 months, less than 50% of infants were exclusively breastfed through 3 months and about 25% were exclusively breastfed through 6 months.”
The CDC Breastfeeding Report Card provides national- and state-level data to help clinicians, child care providers, and families promote breastfeeding and support the women who choose it. In addition to providing an in-depth look at the numbers, the report compares current findings to the breastfeeding goals outlined in Healthy People 2020. This year, it looked at data on breastfeeding practices and support in all 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, and – for the first time – Guam.
The report is published every 2 years, but the data comprising it are updated annually. The latest rates reflect breastfeeding practices among U.S. infants born in 2015 and are based on results of the 2016 and 2017 U.S. National Immunization Surveys.
Since the first report card in 2007, rates of exclusive breastfeeding at 3 and 6 months have increased. However, although rates for any breastfeeding at 6 and 12 months increased in 2015 from 2014 rates, there was no appreciable increase in exclusive breastfeeding at 3 and 6 months, the report noted. And about 17% of infants who were breastfed at birth still got some formula supplementation in the first 2 days of life.
Recognizing that breastfeeding support at the birth facility is a key driver of success, Healthy People 2020 tracks the proportion of live births in facilities that provided the recommended support. These “baby-friendly hospitals” receive a special designation from the WHO/UNICEF Baby-Friendly Hospital Initiative, and their numbers are increasing, the report noted. In 12 states, more than 40% of births occurred in such facilities, comprising more than 1 million infants in 2015 (26%), and far exceeding the HP2020 8% goal.
In a nation in which many new mothers must return to employment outside the home, breastfeeding support at work is crucial. Just 49% of employers provide breastfeeding facilities for these women, the report found. While this may seem less than optimal, it still exceeds the HP2020 goal of 38%.
“All sectors of society – family and friends, hospitals, health care offices/clinics, childcare facilities, community-based organizations, and workplaces – can play a role in improving the health of families by supporting breastfeeding,” the report said. “To reach their breastfeeding goals, mothers need continuity of care, which is achieved by consistent, collaborative, and high-quality breastfeeding services and support.”
SOURCE: CDC Breastfeeding Report Card
FDA grants accelerated approval for Opdivo in metastatic SCLC
The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.
Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.
Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.
Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.
The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.
The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.
The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.
Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.
Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.
Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.
The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.
The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.
The Food and Drug Administration has granted accelerated approval to nivolumab (Opdivo) for treating patients with metastatic small-cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.
Approval was based on an overall response rate and duration of response in the monotherapy arm of the multicohort phase 1/2 CheckMate 032 trial. Of 109 patients with SCLC and progression after at least one previous platinum-containing regimen, 12% responded to monotherapy treatment with nivolumab regardless of PD-L1 status, 12 patients had a partial response, and one patient had a complete response.
Among responders, the median duration of response was 17.9 months. Results of the trial were presented at the ASCO annual meeting and published online in The Lancet Oncology in 2016.
Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions were pneumonia, dyspnea, pneumonitis, pleural effusion, and dehydration.
The approved dose is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity, the company said in a press statement announcing the approval.
The checkpoint inhibitor was approved for treating patients with metastatic non–small-cell lung cancer with progression on or after platinum-based chemotherapy in 2015.
FDA puts partial hold on trial of vascular agent for AML, MDS
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.