FDA reviewer flunks Chelsea's effort at a comeback for Northera

Chelsea Therapeutics was struggling to overcome a series of setbacks a year ago, which had been crowned by the FDA's rejection of Northera (droxidopa). And then the biotech made a surprise announcement: The agency was willing to consider data from another study it had been working on rather than force the company to mount a new clinical trial. And the news inspired a long run-up in the biotech's stock price ($CHTP).

Until today.

After reading the FDA's internal review of Chelsea's new pitch, some investors are likely to question just why they had become so optimistic about the therapy, which is designed to prevent dizziness and fainting among patients with disorders of the nervous system.

Ahead of the Tuesday advisory committee meeting on Northera, the FDA's Shari Targum concludes that a fresh batch of data failed to deliver the proof needed for an approval, recommending that the experts vote for a rejection.

Shares of the company quickly fell 26%.

The crux of the FDA's problem gets down to the new trial data that Chelsea had hoped would provide the basis for an approval. The biotech had hoped that its 306B study would add additional pivotal data that could convince the agency the drug is effective--after the agency had initially turned its thumb down on the drug based on inadequate efficacy and safety data. But a changeup in the trial design may have fatally damaged the data.

"If we give the applicant the benefit of the doubt, and consider study 306B to support efficacy, the results do not meet the criteria as a "robust" or "strongly positive" single study to support a symptom benefit," writes Targum. "This conclusion is based on the small treatment effect, exceeded by the 3-fold higher intra-subject variability. In addition, more patients on droxidopa (vs. placebo) discontinued prior to the first post-randomization OHSA-item 1 (even if patients discontinuing from 306A are counted in discontinuations in 306B), presenting a dilemma in how to interpret the missing OHSA item-1 data." 

Not only that, she adds, but data from two studies "support a lack of effect durability in this chronic condition."

The bottom line: "This reviewer recommends a Complete Response action (rejection) for droxidopa in the treatment of symptomatic neurogenic orthostatic hypotension (NOH), because of inadequate evidence of effectiveness."

Chelsea clearly faces an uphill climb during the panel session ahead. It will have to bring a great game to the court if it expects to overcome these kinds of doubts. And even if it does pull off a surprise win next week, this kind of review raises serious doubts about the drug's near-term future.

- here's the FDA briefing document (PDF)