Progenics and Salix suffer as FDA blocks constipation drug

The sound of champagne corks should have been ringing through the offices of Progenics Pharmaceuticals last week but, following the surprise complete response letter for Relistor in non-cancer pain chronic constipation, executives were most probably reaching for the tissues rather than crystal flutes. The shock over the FDA’s decision was echoed in Progenics’ shares, which plummeted by 50%.

Many observers had expected approval, but with a no from the regulator and the request for additional clinical trials the drug might have to wait another year before it sees the light of day in its new indication. More worrying is what effect the decision will have on Progenics' and partner Salix Pharmaceuticals’ further plans; while bagging approval in non-cancer pain had been important, and could have transformed the hitherto sluggish performance of Relistor, its other purpose would have been to open the gate for approval of an oral version of the drug.

Trial duration

At the moment it is unclear why the FDA has asked for additional trials of Relistor, as the drug has a relatively clean safety profile and has been used in opioid-induced constipation in cancer patients for four years. What might have spooked the regulator is that its use beyond four months has not been studied. Given that the much larger patient population of non-cancer pain patients are not as seriously sick, it is possible that use could be extended for a much longer time than four months and also that repeat dosing might occur.

If the FDA’s concerns do centre around repeated and prolonged use, then this would also affect the oral version of the drug, which has so far not been administered for longer than 84 days during trials.

The news was also a blow for Salix, whose shares fell by 12%. Expanding Relistor's indications and administration had been one of the big priorities of the group when it licensed the drug back in 2011 for what even at the time looked like a big and risky-looking $60m up-front fee (Salix takes Relistor's commercial reins from Pfizer, February 8, 2011).

Very big numbers

Salix has always been confident about the potential of Restilor, a drug that Wyeth handed back to Progenics in 2009. In previous communications management estimated that the chronic pain indication could boost peak sales to $350m, while the oral version could ensure blockbuster status.

These have always looked like bold claims especially since sales of Relistor were just $27m last year and consensus for 2018, a point where the oral drug might have been on sale for four years, are currently just $308m.

But even ignoring the wild optimism of management, broadening the indication and having a more convenient route of administration beyond injection would almost certainly have boosted sluggish sales.

Relistor is currently approved for opioid-induced constipation in patients with cancer, a population thought to number around 1 million according to Bank of America Merrill Lynch, and getting the green light in chronic non-cancer pain could have increased the available patient pool tenfold. Also, as Relistor in its current form is due to lose patent protection in five years an oral version could have protected the franchise.

So the FDA rejection represents a missed or at least a much delayed opportunity, and shareholders have punished both companies. Salix and Progenics had planned to submit the NDA for oral Relistor during this quarter, and many had been expecting approval by late 2013.

Creeping competition

Meanwhile the regulatory hold-up will help Progenics and Salix’s rivals. Sucampo Pharmaceuticals and Takeda, despite their differences, have filed for approval in the US for Amitiza in opioid-induced constipation. And the tie-up between Nektar Pharmaceuticals and AstraZeneca over naloxegol could present the results of a pivotal trial in non-cancer opioid-induced constipation by the end of the year.

Relistor has struggled to live up to expectations to date, and with the latest setback is showing few signs of a rebound.

To contact the writer of this story email Lisa Urquhart in London at [email protected]