May 8, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor
News that the U.S. Food and Drug Administration (FDA)’s Pulmonary Allergy Drugs Advisory Committee has released its briefing notes ahead of a meeting on Tuesday about whether to approve Vertex Pharmaceuticals ’s cystic fibrosis drug Orkambi may have initially spooked the market, but the company has roared back as Wall Street agreed the document is an overall positive.
Shares Vertex leapt 5 percent in noon trading on Friday, as investors realized the FDA’s notes are unlikely to block approval.
When parsed thoroughly the documents show the FDA believes that there is a statistically significant benefit over placebo in FEV1 but has questions about the small treatment effect and the lack of ivacaftor monotherapy and lumacaftor monotherapy controls in the Phase III trials, said analysts.
The lead biotech analyst at Citigroup, Yaron Werber, said a closer look at the FDA’s notes show the regulator is generally open to the idea of approving Orkambi.
“Given that Orkambi has Breakthrough designation, which provides for enhanced interaction, FDA notes that they and EMA agreed with the study designs and continuously provided constructive guidance,” wrote Werber.
“As such we believe that FDA needs to raise this question for discussion but is supportive of the trial design. The key question is whether the benefit is clinically meaningful. We believe that the AdCom will vote positively for approval of Orkambi given the lack of alternative treatment options for cystic fibrosis patients homozygous for the F508del mutation in the CFTR gene.”
In the documents, the FDA agrees that Orkambi shows statistically significant benefit over placebo in FEV1, regardless of the dose—but still had questions about whether the 2.6 percent and 3 percent FEV1 benefit over placebo is clinically meaningful. The regulator is also questioning the additional benefit provided by lumacaftor given the similarity of the treatment effects seen in the 150mg ivacaftor monotherapy study and Orkambi’s pivotal trials.
As part of that, Vertex has faced a barrage of theoretical situations, including the FDA asking a hypothetical question about whether an ivacaftor monotherapy trial might show similar improvements in lung function and reductions in CF pulmonary exacerbations to those seen by Orkambi. But those questions shouldn’t spook investors, said ISI Evercore analyst Mark Schoenebaum.
“Bottom line: despite the questions raised by the FDA in the briefing documents, we believe that the preponderance of evidence will push the clinicians on the panel (and the FDA) to not withhold Orkambi from F508del patients (nuanced statistical arguments unlikely to sway a panel of clinicians, in our view),” wrote Schoenebaum.
“On the question of benefit the double pill over Kalydeco alone, a post-marketing study if deemed necessary would also be sufficient to resolve this issue,” he said. “Therefore, we believe the risk of regulatory non-approval is still low (not zero!) but that we should all bear in mind that some of the questions raised in the document could make reimbursement discussions outside the U.S. more difficult.”
Werber agreed with that assessment, saying in his own note that so far the questions asked have been helpful and shouldn’t affect Vertex too much going forward.
“We believe that these questions are exploratory in nature,” said Werber. “Since FDA agreed with Vertex on the trial design and provided expert advice on statistical analysis and since Orkambi shows a benefit over placebo, it is very likely to be approved.”
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