1. Anonymous on June 8, 2009 7:35 AM writes...

Once again this raises the question of the ability of the Research Head at Merck is capable of making good decisions (or if his team is capable of making a good decision). Unlike some companies who can't make it a decision, it appears that this crew cannot make a good decision. Perhaps I am forgetting something, but with the exception of Januvia, has anything been approved since they took over? Januvia, as I recall, was already set in motion before he took over.

It raises a question of Board oversight. If Merck is a "research driven company", presumably the Board owns that strategy. If the research has continually made bad decisions (failures are part of the game), then is the Board's responsibility or the CEO's responsibility?

2. darwin on June 8, 2009 7:54 AM writes...

I'm with #1. The number of PIII dropouts seem disproportionate in comparison to other companies, and it seems they were involved with a $300m fiasco PIII several years ago with a BMS agreement that took a nose dive shortly afterwards. Amazing these high dollar decisions seem to fly under the radar with little accountability, considering the remaining 65,000 employees are stuck pocketing soup crackers at Denny's while at conferences in order to stay under their diminishing per diem.

3. cookingwithsolvents on June 8, 2009 8:07 AM writes...

That IS a weird-looking molecule. . .

4. Jonadab the Unsightly One on June 8, 2009 8:55 AM writes...

> There is no good way to spin a Phase III failure.

Sure there is:

"In view of our absolute commitment to the medical field, to quality, and above all to consumer safety, we cannot in good conscience continue to pursue FailedCandidate any longer. We had hopes for this molecule, but BigDrugCo will not bring a drug to market that we believe may be ineffective or unsafe. We will go back to the drawing board, because we are determined to produce drugs that are safe and effective."

5. RB Woodweird on June 8, 2009 9:00 AM writes...

Perhaps naming your compound a varient of ROTFLMAO is not such a good idea?

6. Annie on June 8, 2009 9:44 AM writes...

Have they ever licensed a succesful drug candidate or external deal under this research leader?

7. CMCguy on June 8, 2009 10:14 AM writes...

Granted the noradamantane seems "unusual" but overall the molecule appears well compliant with "Rule of 5" and one assumes (hopes?) there was SAR work that suggested the benefit of such a "bulky grease ball" in that position. Better IMO than sticking biphenyls out there which seem to be everywhere. The thing about admantanes and similar structures is have to consider in 3D both for that portion as well as how it restricts/places the rest of the molecule. It can make it tough choice when a group that may not be aesthetically pleasing seems to be crucial to activity.

In terms of placing "blame" as #1 & #2 do, its too quick to jump on the Head of Merck Research. Derek points out the area is difficult and enough promise in Phase II to push forward into "wider (and more realistic) conditions of Phase III". This implies (to me) perhaps a poor Phase III Trial design but its easy to be a Monday morning quarterback. Agree needs be postmortem to determine if specific "bad decisions" where responsible, and more so if may reflect a "poor environment" for conducting development work or if indeed one of those unfortunate 4/5 (PHMRA) Failed Clinical compounds that do not succeed.

8. NH_chem on June 8, 2009 10:33 AM writes...

While this looks weird, it is right up the alley of many adenosine antagonists. Take a look at compounds at Biogen, Adenosine Therapeutics (now Clinical Data), CVT, and others. That structure is very common in the adenosine world.

9. David P on June 8, 2009 10:47 AM writes...

It is a strange-looking molecule with a strange name too, but it is not so outrageous and they must have compared with other structures. Generally, big companies are pretty conservative about what they let go forward, so they must have had data to support that decision.

I think it is pretty cool to find that cage that fits neatly in the desired pocket. The molecule will be conformationally restricted by that, which can enhance activity.

As for a positive spin, that is a good try, Jonadab, but an awfully expensive bit of PR. :)

10. gallagher on June 8, 2009 3:14 PM writes...

Not knowing a great deal about Merck. How big a blow is this to Merck? Is it likely to have an adverse impact on jobs in the near to medium future?

11. Anonymous on June 8, 2009 8:18 PM writes...

As a ex-Merck employee and knowing the past this does not come as a surprise. People who worked very hard to make things happen for "Merck" day in and day out have been shown the door, and the one they retained at the top never worked! If you work in one way or in other capacity you know what is genuinely out there and learn from it, if mistakes are made. The more they fail higher they climb on the mangement ladder! That is pretty much the truth (Drs. Kim, Hutchison, Metters and the clown Turner). Not long ago the last named was boasting to go big time for licensing and such. Rolofylline, if all all worked out well would have garnered $200 million or so around 2012. Not much money but the fall out from this will impact Merck negatively.

12. Still Scared of Dinosuars on June 8, 2009 9:23 PM writes...

Not sure where all the numbers are coming from, but:
1) $300 million for a failed trial can be pretty cheap in comparison to what it usually costs to by buy a company with a drug ready to go into Phase 3...maybe...but
2) $300 million seems, ya know, pretty expensive for a drugs that "would have garnered $200 million or so around 2012". Just sayin'...

Drugs fail for a lot of reasons in Phase 3, some of them even legitimate, but the first question I always ask is, "Did the sponsor amend the protocol to increase enrollment?" My back of the briefs guess is that when that happends a trial is 3x as likely to fail as compared to trials that don't have to beg for patients. Prove me wrong.

13. Zak on June 9, 2009 5:01 PM writes...

I interpreted for a lot of meetings between NovaCardia and the original owners of that compound. What a shame it didn't make it; everybody had such high hopes.