Monday, October 19, 2009

Wyeth Quits On Relistor; Surprise Victory in First REMS Test Market

It is no surprise that Wyeth is willing to pay $10 million to wash its hands of the opioid-induced constipation therapy methylnaltrexone (Relistor), returning all rights to partner Progenics Pharmaceuticals.

The “transition payment” to unload future obligations is clearly a case of a throwing a bit of good money after bad, when the alternative—continuing to support the product as demanded by the partnership agreement despite negligible sales—would entail throwing a lot of good money after bad.

So it is not a surprise that Wyeth gave up on Relistor per se—but it is a surprise that Wyeth gave up on its opioid-induced constipation partnership when GlaxoSmithKline did not.

This time last year, it sure looked like Wyeth and Progenics had a much better chance of making their partnership work, while GSK—big pharma partner for Adolor’s mechanistically similar therapy alvimopan (Entereg)—had no reason to push forward.

Relistor and Entereg have a lot in common. The two drugs were approved at almost the same time in mid-2008 to relieve constipation in high-risk subpopulations. They share a similar mechanism of action, targeting the mu opioid receptor. Both were small molecules developed by small companies (Progenics and Adolor, respectively); both had big pharma partners eager to commercialize them, eyeing a blockbuster market opportunity: routine use to prevent constipation associated with chronic opioid use.

And both ran aground late in development when safety issues emerged.

That’s when things got different.

Neither product had a smooth path through the "Safety First" era Food & Drug Administration, but Entereg came to market with an ultra-restrictive indication (short-term, inpatient use in post-surgical patients only) and even more restrictive post-controls designed to ensure there is absolutely no long-term or outpatient use. It marked one of the first uses by FDA of its new Risk Evaluation & Mitigation Strategies authority granted by the FDA Amendments Act of 2007—and an early example of how the new tools really can dramatically limit the potential patient population for a new drug. (See “Entering the World of REMS,” The RPM Report, July 2008.)

Relistor was also approved with a narrow initial indication (subcutaneous use for terminally ill cancer patients on opioids), but without any special restrictions upon approval, not even mandatory post-marketing safety studies, making it an increasingly rare example of a new molecular entity approved in the FDAAA era without triggering any of the agency’s new post-marketing safety tools. (See “FDAAA Impact Analysis,” The RPM Report, May 2009.)

It’s safe to say that neither GSK nor Wyeth was thrilled with what they eventually found themselves marketing. But if you had to bet which would give up first, it sure looked like a safe bet that GSK would bow out of Entereg. After all, GSK was stuck with a hospital product instead of a primary care blockbuster; Wyeth at least had access to the primary care market, even if it didn’t yet have a blockbuster indication.

Well, it didn’t work out that way.

Not only did Wyeth give up on Relistor first, it paid Progenics an additional $10 million on top of at least $160 million in milestones and product development costs already paid--just to get the brand off its hands.

GSK, on the other hand, backed out of any further development of Entereg, but the company has continued to market the drug for the approved indication—post operative ileus—despite the strict, hospital-only access program. Entereg’s no blockbuster: with sales of just $5 million in the second quarter, it is not even a rounding error in GSK’s results.

But its doing better than Relistor, which posted sales of only $3.2 million during the quarter. More importantly, Entereg’s modest sales could potentially pay off the modest cost of marketing the drug via GSK’s hospital sales organization.

Not so with Relistor, where even a 10x ramp up in sales would make it difficult for Wyeth to justify continued support for the brand—especially in the context of the now complete Pfizer merger.

So, if (as we suggested at the time of the approvals) Entereg vs. Relistor marked an early case study of competition between products saddled by a REMS and products without restrictions, score a victory for marketing under a REMS.

Okay, we’re not overstating the case here. There’s essentially no way that Entereg will pay back GSK’s investment in the product. But there is also no denying that GSK will end up much better off than Wyeth did with Relistor, even though Relistor had the “clean” approval.

Its not like GSK and Adolor wanted a REMS. But having got one, the companies may end up demonstrating that commercial success is possible despite restrictive programs—and may even be enabled by them, since constraints on marketing by definition limit the marketing investment to commercialize REMS products.

Put another way, if you need to create a new commercial model anyway, it may help to be prohibited from using the old one.


Anonymous said...

That just shows you how crapy this government of our's is. Always scared of people taking drugs. All this drug is like is oxycodone that doesn't cause constipation. Thats awsome. Some more needs to be done to ride this country of dumbass bureaucrats.

Unknown said...

Yea...those dumbass bureaucrats always focused on making sure people don't die from drugs. Off with their heads!!!

Anonymous said...

this makes me sick --the politics of medicine and this rems crap -- I take relistor and I am NOT dying -- I have suffered 30 years of chronic back pain and my gasto doc gave it to me after everythign else failed because i take a lot of meds. and I get very constipated. THe politics of this "shitty biz" pardon the pun" is really scary. So this is how the fate of good and bad drugs are decdied? I think this REMS thing will in time proove just another way a govn't agency spent bliions trying to unsucessfully fix a problem THEY created. Drugs are never going away. Get used to it. This country scares me.

jaymes said...

this country makes me sick -- I take Relistor -- I am NOT dying -- my pain doc uses it OFF LABEL for my chronic constipation from 11 years of chronic opiate therapy for pain -- it has worked, believe it or not, though it took a few weeks to really start working regularly. This medicine is causing me side effects, other than is sucks to have to give yourself an injection to defecate...But it works -- best thign I've ever seen for OIC.

THough I am on many painkillers to help me have a quiality of life, I am far from bedriddin. I am healthy, I exercise, go out to eat, -- but I am disabled with three back surgeries and I must take a huger amount of opiates each day and endure severe nerve pain casued by these surgries. It never goes away and it's very serious -- and now the docs all want to make money of "injections and proceeders" that NEVER work, but they make the patient take them before they will prescribe pain pills. It's like a little money game the docs and the technology and the pharmacutical companies are playing.

THe p ain killers allow a quiality of life that I never would have had had I sought help. They really take the edge off intractable nerve pain 24/7 So I'm REAL constipated. This drug Relistor has changed my life, IT's a SMART DRUG -- It's a good drug -- IT WORKS -- though it was slow to... But it does work, and I'm taking a lot of opiates for pain --- I feel better in my gastro than I have felt in 20 years, long before the second and third surgeries. This drug is IMPORTANT TO MY QUALITY OF LIFE -- but to read that piece of Relistor, the politics behind pharmaceuticals scared me to death -- SO it proves what drugs we take -- regardless of which ones WORK the best -- is still dictated by MONEY by POWERFUL PEOPLE. Who cares which drugs works best? (Reslistor) They got a better offer fromthe other drugsd or something -- It diesn't really matter, the point is that this is WRONG and I will suffer from it. and so will your loved ones and maybe even you.

Like I said, people oday scare me. Pharmaceutical companies scare me. Everything scares me -- and this REMS study stuff I predict will in time prove to be just another way that a gov't agency spent nearly a decade and billions of dollars to stop a problem that THEY started.......And guess what? the problem is still here. DRUGS ARE NEVER GOING AWAY -- they know that. The feds just want to make DAMN sure that the drugs killing US kids are not made my pharmaceutical companies with ties to the US -- they want it to be some nasty meth from a trailer meth lab or some crack found int the panties of some Appalachia they can blame the low class element in this world for problems they create and nurture ---