Oncology postmarketing requirements mostly on schedule

 

Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.

“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.

The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.

The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.

From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.

Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.

The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.

 

“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”

“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”

No disclosures were reported

SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.

 

Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.

“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.

The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.

The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.

From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.

Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.

The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.

 

“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”

“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”

No disclosures were reported

SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.

 

Food and Drug Administration postmarketing requirement (PMR) studies for cancer drugs tend to be completed on schedule, but the drugs can remain on the market even if primary endpoints in those studies are not met, according to a research letter in JAMA Oncology.

“These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators,” wrote Chadi Nabhan, MD, MBA, chief medical officer at Cardinal Health in Dublin, Ohio, and Marjorie Zettler, PhD, MPH, senior scientist at Cardinal Health.

The researchers reviewed the FDA’s Novel Drug Summary and compared the requirements listed there with information in the FDA’s Postmarket Requirements and Commitments database and on the Clinicaltrials.gov website.

The FDA has relied on its accelerated approval program, using surrogate or intermediate endpoints deemed to reasonably predict clinical benefit, in order to balance expeditious approval with patient safety. And it has used postmarketing requirements to try to mitigate the risk of this program.

From January 2011 to December 2016, 49 new drugs were approved in oncology, 23 of which were granted an accelerated approval. Of those 23, 17 had postmarketing requirements to complete, including 34 clinical trials. Of the 34 trials, researchers found, 15 have been completed, 14 are ongoing, 2 have been terminated, and 3 are pending.

Out of the 15 clinical studies that have been completed, 3 failed to meet their primary efficacy end points – for atezolizumab, nivolumab and pembrolizumab. None of the drugs have been pulled from the market, researchers noted.

The two terminated studies, both for idelalisib, were stopped because of safety concerns. One product, ponatinib, was temporarily pulled, and the FDA required further studies, with a risk evaluation and mitigation study. That postmarketing study was eventually resumed and completed.

 

“Recently, the FDA has been criticized for its oversight of PMR clinical studies. The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late,” the authors wrote. “Our own review of PMR clinical studies for novel oncology drug products granted AA [accelerated approval] within the last 6 years found that no studies were behind their original schedules.”

“However,” they went on to note, “PMR studies identified serious safety concerns in two incidents that resulted in changes to the labeling for both products [idelalisib and ponatinib]. In addition, our analysis identified three instances [20%] where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.”

No disclosures were reported

SOURCE: Nabhan C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0610.