Clinical Trial Results Fail to Inspire

The Food and Drug Administration typically requires two phase 3 trials for approval. That rule often leaves drugmakers dangling, with one positive trial under their belt, but the results of the confirmatory trial still pending.

Such moments can seem like good times to own the stock. But in reality, drugmakers waiting on results from confirmatory phase 3 trials are a risky bunch -- investors often assume the second trial will be a repeat of the first, which limits the upside and increases the downside.

Witness Inspire Pharmaceuticals (Nasdaq: ISPH), whose stock dropped by more than half today after the second phase 3 trial testing its cystic fibrosis drug, denufosol, failed to show an improvement in lung function.

The only major difference between the two trials was that first trial tested lung function in patients taking denufosol for 24 weeks, while the second trial extended the results to 48 weeks. The difference doesn't appear to explain the bipolar results -- the second trial took readings at 24 weeks as well, and denufosol didn't improve lung function at that time point, either.

Instead, Inspire seems to have been bitten by the placebo bug. In the first phase 3 trial, the drug increased the amount of air the patient could blow out by 48 ml; patients taking placebo, by contrast, increased just 3 ml.

The successful results of that trial were released in 2008, so the patients in the second trial knew there was a chance that they were receiving a drug that could help them. In the second trial, the lung function increased by 40 ml, but the placebo increased by 32 ml. The smaller-than-expected difference wasn't statistically significant.

Placebos seem to be helping a lot of patients lately. For example, many rheumatoid arthritis patients in the control groups of trials testing Lexicon Pharmaceuticals' (Nasdaq: LXRX) LX2931 and Pfizer's (NYSE: PFE) tasocitinib saw their symptoms decrease, even though they weren't receiving any active drug. There's some evidence that placebos are actually getting stronger.

Inspire hasn't decided exactly what to do with denufosol; it plans to make that announcement in February, but none of the options look particularly good.

Submitting to the FDA with one positive trial doesn't seem like the best move. InterMune (Nasdaq: ITMN) couldn't get Esbriet approved with only one positive clinical trial for a lung disease where there aren't any other options. Since there are several other options for cystic fibrosis patients, such as Novartis' (NYSE: NVS) Tobi and Gilead Sciences' (Nasdaq: GILD) Cayston, I doubt Inspire will be able to get past the FDA.

That leaves Inspire with a tough choice: running another clinical trial or dropping development of denufosol. Neither outcome inspires me to want to buy the drugmaker.

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