J&J Tests FDA's Pain Threshold with Tapentadol

One line in Johnson & Johnson’s press release yesterday announcing the submission of a New Drug Application for the pain therapy tapentadol caught our eye:

"More than 1,800 patients have been treated with tapentadol IR tablets in clinical trials to date."

Which got us thinking: what makes J&J think they can get a new-ingredient product approved as a pain killer at today's FDA with data on only 1,800 patients? Haven't they noticed how tough it is to get new drugs through FDA, especially in the pain category?

Here are some possible answers:

(1) They are self-absorbed egotists with unfounded views of their own power and infallibility. But that can't be it, can it?

(2) J&J thinks that FDA will relent on pain products in the next year or so. It never hurts to be optimistic, but we haven't seen any signs of that yet.

(3) The product is for limited indications; J&J has a risk management program that will assure that it will stay in that population and they will sell the program to FDA as well as the drug’s safety.

Well, the press release says the product is for "moderate to severe pain" supported by studies in "patients undergoing bunionectomy surgery or for patients with degenerative, end-stage joint disease of the hip or knee," supported by a third study in "outpatients with low back pain or pain from osteoarthritis of the hip or knee." So it sure sounds like J&J is going after a big market based on relatively small studies. Not exactly a recipe for success by cautiously selecting a sub-population.

(4) There is something different about the way this product works which means that it will have no safety or abuse issues.

It surely doesn’t sound that way in the press release. J&J says it has "a unique profile with two mechanisms of action, combining mu-opioid receptor agonism and norepinephrine reuptake inhibition in a single molecule." That may be a great profile, but from a safety perspective it suggests a higher burden on J&J to show that the drug is free of two different potential risk profiles.

As for efficacy? According to J&J "data from these clinical trials suggest that tapentadol has efficacy comparable to strong opioids."

Is this a winning profile at today's FDA? We'll all find out later this year.

Read More

Deals of the Week: "King of Pain" Edition

Admittedly, it's been a quiet week for biz dev in pharma land. The big news has been clinical. On the positive side, the diabetes triumvirate of Amylin, Alkermes, & Lilly published studies on October 31, reviewed here , showing that long-acting Byetta has staying power. And then there's the therapeutic effect of good vibrations. On the negative side, GPC's stock price cratered on the news that accelerated approvals aren't really under threat, it's just that satraplatin doesn't work as advertised. Bad news from Lilly and Daiichi too, who announced this week that they are suspending two prasugrel trials due to concerns about side-effects.

And a new survey posted this week--this time from IMS--gives pharma execs yet another reason to worry: US pharmaceutical sales for 2008 are projected to increase at their slowest rate since 1963 as cheaper generic drugs drive down prices and docs write fewer scripts for medicines tied to harmful side-effects. (At least sales are increasing, right?)

But in case you missed them, here's the deal-flow round-up:

• Lilly inked a deal with India-based Glenmark Pharmaceuticals to acquire rights to a portfolio of TRPV1 antagonist molecules, including a Phase II compound, GRC 6211, for osteoarthritic pain. Terms of the deal: Lilly pays Glenmark $45 million up-front and up to an additional $215 million in milestones. The deal's a bit surprising--according to Windhover's Strategic Transactions Database, the pharma has signed only 12 deals in the pain space since 1994 and three of those transactions were out-licenses, including a $211 million deal to NeoSan for US rights to Darvon and Darvocet N.


• King Pharmaceuticals signed a deal with Acura Pharmaceuticals worth $30 million up-front and up to $28 million (per product) in milestones to develop and commercialize 4 of Acura's immediate release opioid analgesics. This isn't King's first foray into pain of course. Nearly two years ago, the company inked a much bigger deal with Pain Therapeutics for that company's Phase II, abuse-resistant, long-acting oxycodone product Remoxy. (See this March 2006 IN VIVO story for more.) Perhaps this week's deal is a signal that King is returning to a specialty focus centered on neuroscience and hospital/ acute care--the "King of pain," perhaps? That may be necessary for the company's survival. Last week King announced it was slashing 20% of its work force after losing patent protection on its heart failure remedy Altace.
  
• Another spec pharma deal: NycoMed announced it was purchasing Bradley Pharmaceuticals for $346 million. The reason: "This brings together the strengths of both companies with the objective of creating a leading specialty pharmaceutical player in dermatology," said Paul McGarty, Chief Executive Officer of Nycomed US, in the company's press release. European spec pharma companies have been knocking on the door to the US via acquisitions--witness also the Meda AB acquisition of Medpointe earlier this year (at nearly $800 mm). We won't be surprised to see more of these.
  
• Finally, on November 1, Merck inked a deal with Dynavax worth up to $136 million for rights to that biotech's Phase III Hep B therapy, Heplisav, which promises an easier dosing schedule and potentially better efficacy in weakened immune systems than the drug Recombivax HB Merck already markets. Heplisav combines a segment of the hepatitis B virus and a DNA sequence that activates a toll-like receptor, triggering an early immune response. While the terms of the agreement weren't overwhelming, it's signing suggests the following: 1) There is still faith in the Toll-like receptor field despite Coley Pharmaceutical's high profile failure last January; 2) Pharmas continue to show interest in vaccines, thanks in part to new adjuvants that allow the development of more potent medicines that also come with higher price tags. (See this September 2006 story by our RPM brethren for more.)

Read More

Another Co-Promote Bites the Dust

When Merck and partner Neuromed yesterday pulled the plug on Phase II chronic pain treatment NMED-160/MK-6721, another co-promote bit the dust, too.

More proof, then, that most co-promote options built into today’s biotech-pharma licensing deals are just window-dressing—comfort cushions for biotech investors dreaming of drug revenues and spec pharma success. Earlier this year we laid out in IN VIVO some of the reasons why fewer than 10% of co-promotes actually turn into market-place reality.

That statistic reassures the Big Pharma partner—most of which hate the thought of sharing their commercial spoils with inexperienced biotech, even if some of them say otherwise. But the main reason co-promote promises don’t often become reality is product discontinuation, as in this case, which helps no-one.

Luckily for Neuromed, the aborted program, an N-type calcium channel blocker, wasn’t its lead. Not since April 2007 anyway, when the biotech licensed US rights to a Phase III extended-release opioid analgesic OROS Hydromorphone from Johnson & Johnson’s Alza.

This deal means Neuromed may yet fulfil its dream, shared with most other biotechs, of setting up its own specialist sales force. And Neuromed may yet get to co-promote products with Merck, since the 2006 deal granted the biotech the option to co-promote to US specialists any N-type calcium channel blockers emerging from the collaboration—and the partners say they’ll keep looking for others.

But with NMED-160/MK-6721 gone, at least in pain, Neuromed will miss out on at least $202 million in milestones, and possibly more. It also paid $30 million up front for OROS. That product had better make it onto the US market (it's approved in Europe, but still not in the US, seven years after an approvable letter ). Otherwise private Neuromed may be in danger of biting the dust, too.

Read More

Ouch. The Pain of Pain

The wheels grind slowly but they sure do grind.

After four years of legal wrangling, this morning, Purdue Pharma--one of the biggest private drug companies in the US--and three top executives pled guilty in Virginia court to mishandling the pre-2001 promotion of Oxycontin, the company's blockbuster pain drug. The punishment: $600 million.

Purdue can afford the settlement; it won't lay off anyone, apparently. Except its own top management--the company's president Michael Friedman, one of the executives pleading guilty--is getting the boot and, according to the New York Times, an $18 million fine; likely to follow is chief legal officer Howard Udell, who also pleaded guilty (and, says the Times, is on the hook for $9 million). The final misdemean-er--former research head Paul Goldenheim--left Purdue in 2004 for Transform Pharmaceuticals, which was sold soon after. He'll owe $7.5 million.

The settlement is bad news--potentially really bad news--for other companies in the pain space, in particular Cephalon and Endo. Both of these public companies are being investigated for over-aggressive promotion. If those two companies end up with a settlement anything like Purdue's--and federal and state attorneys are likely to feel pretty good about their chances, given the success of the Virginia US attorney--the picture won't be pretty.

Purdue itself, leaderless now, will drift. The company's hired Russell Reynolds to do a CEO search, but no one's looking forward to that one. Friedman, the first non-Sackler to run Purdue, had spent 20 years building up the trust of the family, hardly an easy group to work for. Indeed, talk about an insider board: Purdue's has members: the 90-plus year old founding brothers, Mortimer and Raymond Sackler; their wives; and the founders' four adult children.

They could bring in an internal candidate--like Ed Mahony, the current CFO, a savvy finance guy who's managed to keep enough cash to pay the fines. Or they could bring on someone from one of the international affiliates. Possibles: John Stewart, a long-time employee who manages the Canadian, New Zealand and Australian businesses, or--less likely given his shorter tenure--Ake Wikstrom, the GM of Munidpharma in Europe.

But no Sackler is likely to step in and settle all this hash. None of the 2nd generation Sacklers have ever managed the company. When times were good, the family rejected many offers to buy the business, or take it public. Now that times are really bad--and now that the family doesn't have a CEO they can depend on--they may just decide enough is enough.

In fact, the whole scandal could really be laid at the doors to the family's often empty offices at Purdue's headquarters: though they approve decisions, they let others watch what is a deceptively simple business. In selling addictive pain drugs, there are lots of complex details to follow. For too long, Purdue's management didn't recognize them; neither did its board.

That complexity colors the benefits of the whole pain strategy. Purdue, like Cephalon and Endo, are in the pain business because they can minimize R&D risk with high-margin reformulations of old and effective pain drugs. But there's no free lunch: the risk they avoid in development they run in the marketplace selling opiates.

Already, many pharma companies--AstraZeneca and Pfizer being two recent examples-- are being roasted for promotional improprieties. With Purdue's blood in the water, the legal sharks aren't likely to grow any less hungry.

Read More