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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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September 25, 2013

Sugammadex's Problems: Is the Merck/Schering-Plough Deal the Worst?

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Posted by Derek

That didn't take long. Just a few days after Roger Perlmutter at Merck had praised the team that developed Bridon (sugammadex), the FDA turned it down for the second time. The FDA seems to be worried about hypersensitivity reactions to the drug - that was the grounds on which they rejected it in 2008. Merck ran another study to address this, but the agency apparently is now concerned about how that trial was run. What we know, according to FiercePharma, is that they "needed to assess an inspection of a clinical trial site conducting the hypersensitivity study". Frustratingly for Merck, their application was approved in the EU back in that 2008 submission period.
Sugammadex_encaps_rocuronium.jpg
It's an odd compound, and it had a nomination in the "Ugliest Drug Candidate" competition I had here a while back. That's because it works by a very unusual mechanism. It's there to reverse the effects of rocuronium, a neuromuscular blockade agent used in anaesthesia. Sugammadex is a cyclodextrin derivative, a big cyclic polysaccharide of the sort that have been used to encapsulate many compounds in their central cavities. It's the mechanism behind the odor-controlling Febreze spray - interestingly, I've read that when that product was introduced, its original formulation failed in the market because it had no scent of its own, and consumers weren't ready for something with no smell that nonetheless decreased other odors). The illustration is from the Wikipedia article on sugammadex, and it shows very well how it's designed to bind rocuronium tightly in a way that it can no longer at at the acetylcholine receptor. Hats off to the Organon folks in Scotland who thought of this - pity that all of them must be long gone, isn't it?

You see, this is one of the drugs from Schering-Plough that Merck took up when they bought the company, but it was one of the compounds from Organon that Schering-Plough took up when they bought them. (How much patent life can this thing have left by now?) By the way, does anyone still remember the ridiculous setup by which Schering-Plough was supposed to be taking over Merck? Did all that maneuvering accomplish anything at all in the end? At any rate, Merck really doesn't seem to have gotten a lot out of the deal, and this latest rejection doesn't make it look any better. Not all of those problems were (or could have been) evident at the time, but enough of them were to make a person wonder. I'm willing to nominate it as "Most Pointless Big Pharma Merger", and would be glad to hear the case for other contenders.

Comments (29) + TrackBacks (0) | Category: Business and Markets | Clinical Trials | Pharmacokinetics | Regulatory Affairs | Toxicology


COMMENTS

1. petros on September 25, 2013 8:47 AM writes...

And in 2007 the development team got the RSC BMCS' Malcolm Campbell award (a med chem prize)

Jonathan Bennett, Anton Bom, Alan Muir, Ronald Palin, David Rees and Ming Zhang. all then of Organon but now?

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2. Anon8 on September 25, 2013 9:23 AM writes...

Another crappy boondoggle from this deal! No doubt greedy Freddy is real rascal here along with the Dick from Merck. Feel sorry for the Merck Chemists and others who have been fooled. Did you all hear that Prof. Phil Baran is the latest recipient (for the year 2013) of MacArther genius grant! Readers, Is there any other organic chemist who have won this award in the past?

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3. Chemjobber on September 25, 2013 9:28 AM writes...

@2: Yes. Bertozzi, Kiessling, Sanford.

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4. Jazel on September 25, 2013 9:45 AM writes...

Correction: brand name is Bridion :)

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5. annon8 on September 25, 2013 9:59 AM writes...

@ CJ: Thanks!

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6. Eric on September 25, 2013 10:09 AM writes...

As a former Merck employee who left pre-merger when the mantra was "we WILL NOT merge!", I very much hate this merger, and I think that Merck got conned. They did get one thing from the reverse merger, though. The whole point was to not lose Remicade to J&J by the acquisition clause of the licensing agreement. That was shady at best, but it ended with a settlement that was better than the result would have been if Merck bought SP directly.

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7. simpl on September 25, 2013 10:30 AM writes...

If the FDA doesn't trust the paper trail - hard to maintain through two takeovers, I expect - they don't care to move. Too bad for the science, the users and the product, which sells well enough in other countries.
The case begs the question of how Bridion and recent drugs not approved in US are doing in EU, and vice versa. Anyone got figures?

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8. Anchor on September 25, 2013 10:31 AM writes...

@6 Likewise, the SP employees feels that Merck conned them. What do you say to that? I think all those hard workers at both places rightly feel that the goons in the upper management system conned them, collectively.

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9. Lyle Langley on September 25, 2013 11:23 AM writes...

Not sure Bertozzi or Keissling really count as organic chemists. Sanford and Baran would be the only 2 winners.

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10. Matthew Herper on September 25, 2013 11:27 AM writes...

It's worth noting that Merck's PD-1 antibody was an Organon compound. That's currently their big experimental hope.

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11. drrpm on September 25, 2013 12:51 PM writes...

Its disappointing to hear that approval for Sugammadex was denied again. It would be a very useful drug in certain circumstances. I had a case yesterday where I would have used it if it was available.

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12. DCRogers on September 25, 2013 1:04 PM writes...

The Organon site is a great example of the value destruction inherent in merger-mania.

Head-count are not independent cells that can be moved without cost anywhere in the corporate body; they have assembled into larger organs whose value is greatly reduced if atomized, even if you keep and move each of the individual cells somewhere else in the new hierarchy.

I don't think the bean-counters appreciate the devastation of productiveness caused by serial mergers and reorgs.

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13. emjeff on September 25, 2013 1:49 PM writes...

#12, they appreciate it, alright, they just don't care. These mergers are very seldom done to actually increase value. For example, the reason BMS bought Dupont Pharma back in 2001 was not to "create shareholder value", it was to dump cash so that they themselves would not be bought.

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14. Anonymous on September 25, 2013 2:07 PM writes...

Derek, I would like to dispute the worst merger title. I don't have any insider's information, so the following is just my guess.

I suspect the Merck-SP merger was a business decision. In March 2009, right before the merger, Merck's stock price had dropped to ~$25, which put its market cap at around 50B. With this market cap (which put it the No. 8 big Pharma in the US, behind Pfizer, GSK, and even Amgen), it became quite conceivable that Merck could become a takeover target. To prevent this from happening, Merck will need to bulk up. It did not want to merge with anyone at its size or bigger for fear of losing control of the board, and they have to do it fast. BMS and SP were the only two legit targets (big enough to bulk up the market cap, small enough to let MRK control the board). SP became the easy one because Freddy, SP's CEO, was known for his salesmanship.

It was all about the survival of Merck perceived by the then CEO Dick Clark. The pipeline was in the equation and I don't think it was the deciding factor.

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15. Chris on September 25, 2013 2:40 PM writes...

Bridion is without doubt one of the greatest innovations in anethesiology in the last 20 years. Its just a shame it costs so much and a shame that Merck and SP made such a mess getting on to the market in the US.

The upheaval of the mega merger is indeed destructive!

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16. Anonymous on September 25, 2013 3:18 PM writes...

Since one of the consequences of the SP-Merck reverse merger was the closure of some of the most productive research labs from both SP (Newhouse) and Merck (Montreal), I say "yeah, this is arguably the worst pharma merger of all time".

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17. anonymous on September 25, 2013 7:32 PM writes...

Well one things for sure, the carnage (headcount reductions) isn't over yet....not by a longshot !

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18. Fraggle on September 26, 2013 3:23 AM writes...

Well Europe and Japan have no problem with bridion. Several anaesthetists I have spoken to think its great bar the cost.

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19. A Nonny Mouse on September 26, 2013 3:25 AM writes...

Why don't they just use self destructing cis-atracurium instead?? No, there is no real problem with histamine release, it's just as bad with rocuronium, if not worse.

PS, David Rees poured a pint of beer over my head in 1979 when I said something derogatory about Liverpool football (soccer) team. His father would not left him work in our group anyway (that was his interview in the pub for a PhD place- he failed as he should have drunk the beer instead).

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20. SteveDoc22 on September 26, 2013 8:32 AM writes...

In answer to the question of why the Merck-Schering deal was structured as if Schering were acquiring Merck, it was to avoid a change-of-control clause that would have forced Schering to return ex-US Remicade rights to JNJ. MRK lost in arbitration anyway because it was obvious that MRK had,in fact, acquired Schering, despite protests to the contrary.

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21. drrpm on September 26, 2013 11:10 AM writes...

To A Nonny mouse: While Cis-atracurium may "self destruct" it does not happen quickly enough if rapid reversal is needed. Also, the aminosteroid agents generally work better in clinical practice.

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22. Anoninsider on September 26, 2013 2:40 PM writes...

MRK-SP is the worst merger in the history of pharma, hands down. The results of the merger have been: massive layoffs, weak(er) pipeline, crushing budget constraints and a dispirited company culture. Not a single product touted during the merger has made it to market (suvorexant, sugammadex, vorapaxar, etc.). Merck should have overpaid for Amgen, Celgene or even Biogen Idec - they'd be light years ahead of where they are today.

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23. Anonymous on September 26, 2013 6:27 PM writes...

"MRK-SP is the worst merger in the history of pharma, hands down. The results of the merger have been: massive layoffs, weak(er) pipeline, crushing budget constraints and a dispirited company culture."

And how does that differ from any other pharma merger?

"Not a single product touted during the merger has made it to market"

Sounds like Merck Serono, their entire pipeline collapsed.

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24. petros on September 27, 2013 2:18 AM writes...

The GSK merger was pretty dire. From memory 1 of the touted star drug products made it to market and it hasn't proved spectacular

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25. Jacob_23 on September 27, 2013 3:18 AM writes...

"MRK-SP is the worst merger in the history of pharma, hands down."

How about AstraZeneca buying Medimmune?

"No! No, I won't have that! There's a place in Eastbourne."

Major Gowen, c 1976

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26. Chemist turned Hedgie on September 27, 2013 6:13 AM writes...

My money too is on AZN/Medi or Merck/Serono, but it would be rude not to mention a rather special in-licensing- Lundbeck's partnering of Myriad's Flurizan (tarenflurbil). Signed in May 2008, failed in P3 in June 2008.

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27. JJ_gas on September 28, 2013 7:01 AM writes...

Sugammadex is a truly lovely drug to use. I'm a consultant anaesthetist in the UK and it is available here. Turns off Rocuronium like a switch while alternatives all take ages if they work at all. Costs £55 per dose so only non-NHS patients get it :(

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28. Lunar landing on September 30, 2013 8:16 PM writes...

This merger along with the HR-centric management style of Gilmartin destroyed Merck's once stellar scientific and corporate reputation. RIP mother Merck.

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29. Rob in Canberra on April 23, 2014 7:18 AM writes...

We have had Suggamadex in Australia for over 3 years now. It has revolutionised our practice. Turns rocuronium off 100% in one circulation time. Magic. Can also be used in anaphylaxis to rocuronium. Cost is coming down - deal is the more we use, the lower the price.

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