Advanced Life Sciences reeling from FDA rejection

Just ten years after the company was established, Advanced Life Sciences’ (ALS) future is in the balance following a negative efficacy verdict yesterday by an FDA advisory committee reviewing its application for Restanza (cethromycin), a ketolide antibiotic to treat mild-to-moderate community acquired pneumonia (CAP).

Although the panel was largely in favour of the drug’s safety, an important win given the serious safety scares which derailed Sanofi-Aventis’ Ketek as the only approved ketolide, the experts voted strongly against Restanza’s efficacy. ALS’ significant challenge now is to persuade the FDA that the panellists got it wrong when assessing the drug’s efficacy and prevent the PDUFA of July 31 becoming another major setback. ALS’ shares have crashed 75% to $0.35 since the votes were announced, unsurprising given the company’s perilous cash position and the fact that just about everything was riding on a positive review of Restanza (Event - Advanced Life Sciences' antibiotic panel should be revealing, May 22, 2009).

Moving goal posts

The panel voted 11-3 (with 1 abstention) in favour of the drug’s safety, but also voted 11-3 (with 1 abstention) that Restanza did not demonstrate adequate efficacy in the treatment of CAP.

This vote against the drug’s efficacy, when compared to existing antibiotic clarithromycin, was based on the FDA’s experts applying a new set of non-inferiority guidelines for antibiotic drugs that were not in place when the phase III trials were initiated by ALS in 2005.

In addition, the panellists decided to exclude mild CAP patients, those with a PORT score of 1, from the sensitivity analysis, eliminating around 50% of participants in the two phase III trials, despite the mild-to-moderate setting being sought for Restanza.

Clearly ALS will be challenging the FDA’s analysis of the drug’s efficacy data, although they will likely have their work cut out given the regulator's recent track record on applications for new antibiotics.

Despite strong claims from the companies and medical community alike for new treatment options to counter widespread bacterial resistance to current drugs, the FDA is clearly taking a tough stance and indicating that marginal non-inferiority is not satisfactory.

The FDA’s negative verdicts late last year on Arpida’s iclaprim and Targanta’s oritavancin are indicative of this tough stance and that the agency is sticking to its guns on applying new efficacy guidelines even if pivotal trials, approved by the FDA, were initiated and conducted before these revised guidelines came into effect.

Walking a tight-rope

Although ALS has $2m cash at hand and has the option to draw down a further $12m over the next 15 months from a committed financing agreement, the outlook for the company appears fairly bleak.

Assuming the agency adopts a similar stance to their advisory panel, the only way that ALS is then ever likely to get Restanza past the FDA would be to conduct further costly clinical trials, far in excess of current cash reserves.

To compound matters for ALS, the FDA’s review of Restanza is likely to have poured large volumes of cold water on any partnership talks that the company claims are in advanced stages in the US, Europe and Latin America, delaying or even removing another potential source of cash injection.

Therefore, barring a recovery of Vanda-like proportions, at the very least ALS will have to go the way of many a biotech in the recent times and cut its workforce, which would be the second such cull since a 30% reduction in headcount in February.

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