Analysts Say FDA’s AdCom Vote on Vertex No “Slam Dunk,” But Should be Enough for Now

May 12, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor

News that the U.S. Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals ’s cystic fibrosis drug is “not a slam dunk” but should be enough to convince the market the treatment has some upside, analysts said of the decision Tuesday. A delegation of executives of Vertex successfully argued today before the FDA’s Pulmonary-Allergy Drugs Advisory Committee cystic fibrosis drug Orkambi has merit, after the panel voted 12-1 to approve the drug. There had been some concern the treatment may not be approved after notes form the panel leaked last week showing the FDA had significant concerns about the efficacy or Orkambi.

But investors who had been waiting all day for the news and applauded the decision, pushing Vertex up almost 9 percent in aftermarket trading.

Still, the breakdown of the vote wasn’t totally conclusive, with several analysts saying while it may be good enough for now, it was by no means a “slam dunk” for Vertex.

“The FDA panelists grilled Vertex during the Q&A session, with questions about the magnitude and meaningfulness of benefit on the primary and secondary endpoints, the quality of measurement of reduction of pulmonary exacerbations, and the contribution of lumacaftor,” wrote Geoffrey Porges, an analyst with Sanford Bernstein.

“The majority of the panelists seemed skeptical about at least one or more of Vertex's claims, but whether this means they will vote to deny a drug with some demonstrated efficacy (no matter how small), and good safety is in our view, less likely,” said Porges. “The discussion section of the meeting is now ongoing.”

But however ongoing those discussions are, today’s vote was enough to put Orkambi into the running and should be considered “general support” for the drug, wrote biotech analyst Mark Schoenebaum in a note Tuesday.

“Despite the questions raised by the FDA and the panelists' willingness to consider the FDA's arguments this morning (after multiple speakers during the open public hearing), the panelists this afternoon came out in general support of Orkambi,” he wrote.

“The panelists generally agree that a comparative efficacy study of Orkambi vs Kalydeco in homozygous F508del patient could be done post-approval if necessary,” he said.

The breakdown of the questions and notes on the vote are as follows, per Schoenebaum’s note to investors.

1. Discuss efficacy for Orkambi in homozygous F508?
Panel supports efficacy of Orkambi in F508del homozygous...

Comments: FEV1 improvement small but SS and impressive. Improvement in BMI meaningful. Patient testimonies clear that weight gain and bowel discomfort. Exacerbations drive disease along but despite stats impressive reduction in exacerbation. Agree efficacy looks good on many parameters. Question of monotherapy, don't think know from data we have, but don't that that is really important. Speakers eased concern about QOLs but believe secondary endpoints are critical. But concerns about 3 percent FEV1 benefit addressed. Efficacy endpoint met and clearly efficacious. And endpoints go on endpoint. Kalydeco monotx digressing. FEV1 is a surrogate. Exacerbations are what matter. There seems to be efficacy for combo. Benefit maybe better for non-pulmonary endpoints. Unclear why pbo arm. Don't see a lot of toxicity. Would be bothered by delaying. Should slow progression of disease but don't have five years to do that. Have to live with decision that were made before

2. Discuss efficacy for Kalydeco in homozygous F508?
Panel does not believe that available data sufficient to determine efficacy of Kalydeco in homozygous F508 but does not believe relevant for purposes of Orkambi approval...

Comments: Don't think we have useful Kalydeco monotherapy data. Not supposed to manipulate old data to compare and then give weight to actual well run trial. Kalydeco monotx was not efficacy study, not designed such. Decision was then made. But can't now use that data to make decision. After this meeting, may be feasible to do study vs Kalydeco. Have to deal with data we have. Comparator efficacy study. All agree don't have the data to make statement whether combo more effective than monotherapy.

3. (vote) Do data demonstrate that lumacaftor contributes positively to efficacy as part of combo?
a. Yes → 3
b. No → 4
c. Cannot determine → 6

Panel does not believe available data sufficient to determine with panelists who voted "no" and "cannot determine" for the most part falling in the same camp.

Comments: Don't think have data to do comparative efficacy question. No and cannot determine = synonymous. Yes for convoluted reasons - lumacaftor negative effect and ivacaftor alone did not have huge effect. Biologic argument but clinical data range of effects similar so not sufficient evidence. Yes.

4. Discuss safety of Orkambi
Panel agrees that Orkambi appears safe.

Comments: As much if not lower exposure to Kalydeco and metabolite despite higher dose of Kalydeco.

5. (vote) Do data support safety of Orkambi?
a. Yes → 13
b. No → 0

Comments: Hints of possible adverse effects but manageable and large study despite orphan disease.

6. (vote) Do efficacy and safety data support approval?
a. Yes → 12
b. No → 1

Comments: No vote - would've voted yes but because can't determine efficacy. Based on data have on hand… Difficult vote for me but strong unmet medical need and some patients truly responded. Trials met endpoints, reassured, closely followed patients. From data we have… lack of decline over 48 weeks and steady increase impressive. And any reduction in exac extremely important.