Friday, February 28, 2014

More On Dr. Sable's "Likely Unique" Suitability For the SCYNEXIS Chief Science Role


More of the "inside baseball" story is emerging -- on Dr. Sable's move to Chief Science Officer at SCYNEXIS, via the blogging staff at FierceBiotech, this afternoon. It seems that she may have worked on the lead candidate, SCY-078, a treatment for Candida and Aspergillus pathogens when it was owned by Merck. After several Phase I studies, Merck out-licensed it to the company last year, apparently.

From the FierceBiotech piece then -- a bit -- do go read it all:

. . . .[SCYNEXIS], which spun out of a pre-Sanofi Aventis in 2000, believes its oral and intravenous SCY-078 can treat infections tied to the Candida and Aspergillus pathogens, which account for about 85% of invasive fungal ailments in the U.S. and Europe, according to Scynexis. Merck discovered the drug and ran 7 Phase I trials on it before licensing it out to Scynexis last year, the company said, and now the biotech plans to spend the majority of its raise getting an oral formulation into a Phase II study in Candida infections, expecting to kick off enrollment in the second half of this year.

Scynexis pegs the global market for drugs like SCY-078 at around $3.6 billion, and, thanks to the treatment's promise in drug-resistant strains and oral availability, the company believes it can carve out a sizable share of that space. . . .


I am certain that -- even if she never worked on what became SCY-078 while at MRL, her background makes her a great fit. But I now have a hunch that she did do some of the early work on SCY-078 (as she was working in the same research and development area from 1995 on, while at Merck), and thus may be able to deliver some real inside know-how -- given that Merck's out-license of it last year likely frees her from that part of whatever her non-compete might say. Fascinating. We will keep an eye on this.

DoJ Closes Merck's 2010-era FCPA Jacket -- Good News.


Last week, Baxter let it be known that it too had heard from DoJ, and the files were being closed. This is part of an almost industry wide probe.

In Merck's Form 10-K, Whitehouse Station now discloses it has been notified that the investigation is concluded. Not surprising, and recall that this is earlier, and not the same as the Chinese hotel referrer payments investigation of mid-2013. That one is ongoing -- and includes Glaxo, AstraZeneca (and others well-beyond Merck).

That's about all I've got -- for this Friday afternoon.

Be well -- and be excellent -- all weekend to one another.

Merck Saw 33,100 Jobs Ghosted -- Just Since Schering-Plough Wipe-Out, November 2009: "Thanks Again, Fast Fred!"


If we add legacy Schering-Plough job losses to those at post bust-up Merck -- and look back about two years more -- or six years overall -- that same figure would be close to 65,000 jobs eliminated.

Being an entirely reasonable man, I cannot lay the legacy Merck, premerger job losses at Fast Fred's feet -- but I can hold him responsible for the 14,000 jobs lost at legacy Schering-Plough prior to the November 2009 bust-up, and all of these post merger 33,100 are on his tab, in my book, so Fred Hassan directly or indirectly destroyed around 48,000 careers, in just under six years.

For his trouble, he took away, all in -- about $325 million (if he held on to most of his merger transaction equity payouts), in Merck's current NYSE stock price, pension enhancement benefits, bonuses, golden parachutes and all other cash compensation. God Bless America(!) -- she gets just about the sort of business leadership she. . . deserves.

From page 83 of the SEC Form 10-K, filed overnight, then:

. . . .Since inception of the Merger Restructuring Program through December 31, 2013, Merck has recorded total pretax accumulated costs of approximately $7.2 billion and eliminated approximately 26,880 positions comprised of employee separations, as well as the elimination of contractors and vacant positions. Approximately 6,300 position eliminations remain pending under this program as of December 31, 2013, which include the remaining actions under the 2008 Restructuring Program that are now being reported as part of the Merger Restructuring Program as discussed below. . . .


To be fair, Tom, Tom, Brent and Carrie also share blame here -- and between them, with Fred -- the figure received over those six years, all in is now north of $600 million. Disgusting.

That executive team wiped out the equivalent of entire smallish New Jersey township's population -- and pocketed almost two thirds of a billion to do so.

And we haven't even mentioned the securities fraud (alleged, and now settled) -- they committed, that cost Big Merck and its insurers $688 million, during the same period. Fabulous.

Seamus Fernadez At Leerink Swann Keeps Merck's 12 Month Price Target Very Near Current Market Price -- At $57


As a rule, over the last three or so years, Mr. Fernandez has held Merck's one year forward price target well below the levels his peers -- over at JP Morgan, Morgan Stanley, Credit Suisse and Goldman Sachs to name a few, have articulated. His last widely disseminated price target was $48.45, back in August of 2013.

I like his independence -- and his rather skeptical eye. [Leerink's investment banking/M&A advising business lines have essentially no chance of winning Merck's business -- so it never competes for Merck's capital markets business allocations. The opposite is true of all the other four I named.] Sheamus has been closer to right than these other four, of late, on most Merck-related forward-looking guesses. Overnight, he bumped up his price target, but only to less than two per cent above today's NYSE price. He is saying that Merck is fully valued here. And I think I. . . agree.

From the online edition TickerReport (okay!) -- here's the bit:
. . . .Analysts at Leerink Swann boosted their price objective on shares of Merck & Co (NYSE:MRK) from $49.00 to $57.00 in a research report issued to clients and investors on Thursday, AnalystRatingsNetwork reports. Leerink Swann’s target price would indicate a potential upside of [only] 1.30% from the stock’s previous close. . . .


We will keep you posted.

It Has Been FOUR DECADES Since Research On ONE Drug Candidate Was Considered A "Material" Risk Factor As To All Of Merck's Worldwide Revenue


Long after the NYSE closing bell tonight, Merck filed its Annual SEC Form 10-K, and while I will have other posts in the coming days (and weeks) -- as to the interesting matters discussed in it -- this one literally leaps off of page 19. I've not done a completely definitive and exhaustive search yet tonight, but it would preliminarily seem that it has been about four decades, or 40 full years (and perhaps many more), since the behemoth Merck last labeled the research being conducted on any one drug candidate as a "material" risk factor -- for the whole company's fortunes, world-wide.

But that is what is disclosed tonight, as to pembrolizumab, or MK-3475. Wow. With over $44 billion in 2013 worldwide revenue, that disclosure implies (to seasoned SEC lawyers) that spending on this one drug (or, biologic, to be more technical about it -- but remember 40 years ago, Merck had no protein chain biologics research & development programs in its pipe -- only chemical drug compounds). . . is material, to that number. Normally that would, in turn, mean that the spending is approaching 5 per cent of revenue. So -- Merck may be spending $2.2 billion over the next 12 rolling months, on MK-3475. That's one BIG hairy science bet, given that Whitehouse Station likely already had over $2 billion invested in the program, at year end 2013.

To be fair, this disclosure is an "Is the glass half full, or half-empty?" sort of conundrum: by that I mean I pretty firmly believe MK-3475 will be a very successful biologic franchise in oncology (so too do most Wall Streeters). And so, spending very heavily now, to well-arm and position it across several additional types of cancers -- with solid clinical trials data (especially in combination with existing market-leading therapies, in those other oncological settings) makes for an excellent business strategy. But it is far from risk free. Spending perhaps $4.5 billion on one bet, even if MK-3475 turns out to be every bit as efficacious as hoped, doesn't guarantee market leadership.

Why? Well, because as we've repeatedly noted, BMS has an anti PD-1 candidate called nivolumab. And most Wall Street analysts presently have the future $25 to $35 billion market for an effective anti PD-1 biologic splitting 65-35 in favor of BMS's nivolumab. That still leaves Merck's pembrolizumab with perhaps $8 to $12 billion in peak sales -- but places BMS in a position to crowd Merck considerably, should it reach market in the heavy burden cancers first. The only thing that is certain now, is that this is going to be a very fascinating, wildy high stakes game of poker, between two (or three) of the largest drug companies on the planet. Just last week, Novartis bought a seat at this table. So we shall see.

In any event, from page 19, "Risk Factors," then:

. . . .The Company is devoting substantial resources to the development of MK-3475, Merck’s anti-PD-1 immunotherapy, and there can be no assurance that it will be approved for marketing by the FDA.

On January 13, 2014, the Company announced that it had initiated a rolling submission to the FDA of a BLA for MK-3475, the Company's anti-PD-1 immunotherapy, for patients with advanced melanoma who have been previously treated with ipilimumab. The Company also stated that it expected to complete the submission in the first half of 2014. There can be no assurance that the Company will complete the submission, or that the FDA will approve MK-3475 for marketing and sale in the United States for the initial indication or for additional indications. In addition, if approved, there can be no assurance that MK-3475 will succeed in the marketplace. . . .


Don't get it twisted -- I love the audacity, here. And I genuinely hope it pays off fabulously, for Mr. Frazier. He has earned a big win, that much is certain. He did so, by being very careful to this point -- by largely keeping the powder dry. Now he taking one big cannon shot -- he is making a very big bet. Yep. I love it. Go man go!

[I apologize. I am having trouble putting into perspective just how big a sea change this is -- making one big bet, as opposed to hundreds of much smaller ones. I do think it a smart bet. But it is decidedly unlike the Merck of the last three decades, and more like the Merck of a half-century or more, ago. Whoosh!]

Thursday, February 27, 2014

Still No U.S. Confirmation -- On Iran-Merck Story -- Beginning Day Three


A few more Islamic business news sources are now running that item I mentioned yesterday morning.

Still no official word out of Darmstadt, Germany (or Whitehouse Station) -- and neither of the two may ever officially confirm, given the immateriality of it to overall consolidated global operations, and the potential for at least some controversy. To be clear, there is no logical reason why the poor and sick of Iran should be punished for the continuing odious behavior of an oligarchy. The people are effectively without a voice. So I support Merck's move. We will keep watching, though -- here's a bit from the latest version:

. . . ."A[n unnamed] Japanese company has also signed an agreement for the production of medicines in Iran," he added.

MSD is the first US drug company to sign a cooperation contract with Iran since the 1979 Islamic Revolution. International sanctions against Iran have hindered medicinal trade, as pharmaceutical firms have been refusing to sell Iran drugs due to difficulties in receiving payments. This has led to shortages of some vital medicines in the country.

Iran's Health Ministry official, Hossein Ayati, said earlier that 97 percent of Iran's required medicines are currently produced domestically. . . .


Do stay tuned.

Wednesday, February 26, 2014

Is "Our" Merck Poised To Be FIRST US Pharma Co. To Contract Manuafcture Drugs INSIDE Iran?


At the outset, the caveats: only two small news organizations are reporting this (that's the Russian one), overnight -- but both clearly identify the party as MSD. Both call it the US multinational pharmaceutical concern. Even so, we have seen deep confusion about which is the German KGaA named Merck, and which is "our" Merck (US). . . for decades.

And, it would be more likely that a German company would actually build contract manufacturing operations inside Iran, as opposed to a US concern -- given the stultifying answers to Questions 170, and 171, in this US Treasury, Office of Foreign Assets Control Iran Sanctions primer. [One may be deemed to have violated the US law -- by receiving payments from Iran -- even if the transaction that generated the payment was exempt from the law -- i.e., delivery of life-saving medicines. Ugh.]

Having said that, in January 2014, the P5+1 powers signed an expanded access framework for humanitarian engagements -- in Iran. This arrangement, if it exists at all -- and were properly structured -- would easily qualify. Moreover, to be sure -- there are hundreds of thousands of Iranians with life threatening cancers, diabetes and who are afflicted with AIDS, or are living as HIV positive. So, is it "our" Merck that is going to be the first US pharmaco to use these P5+1 protocols to deliver meds, on the ground and in-country, from contract manufacturing sites -- from Tehran or elsewhere? We shall see. Here is a bit of one account -- from inside Iran -- so take it with some salt (and the only other source is Russian language -- so who can say for certain?):

. . . .A major U.S. pharmaceutical company, Merck Sharp & Dohme (MSD) has signed a contract for the licensed production of medicines in Iran, head of Iran's Drug Importing Union, Nasser Riahi said, ISNA news agency reported on Feb. 25. . . .

"The U.S. MSD which is one of the largest pharmaceutical companies in the world wants to manufacture its products under license in Iran," he said, adding that in order to gain the trust of the Iranian partner, the U.S. company has reduced its product prices by 30 to 40 percent.

Riahi remarked that major Swiss-based multinational drug maker Novartis has started production in Iran and signed a contract. A Japanese company also has signed an agreement for the production of medicines in Iran, he added.

He remarked that the MSD is the first U.S. drug company which has signed a cooperation contract with Iran since the 1979 Islamic revolution. . . .


We will let you know if/when Whitehouse Station verifies this is -- in fact -- our Merck, and not KGaA.

Tuesday, February 25, 2014

No Surprise, After June 2102 FDA Clank: Merck Tells Ariad "It's Not You; It's Me. Wait. It's. . . YOU." -- Rid Of Ridaforolimus Obligations


Ariad just made it made it official, but we all knew this was coming, back in June of 2012 -- as I wrote then. The breakup is finally complete, as of this past week. Merck served its notice.

"We're just. . . friends. Not room-mates any more." Heh.

Here's a bit of the very-cogent take of FierceBiotech; do go read it all:

. . . .Ridaforolimus, an mTOR inhibitor with potential in various cancers, made its way through a Phase III trial in advanced sarcomas, but the resulting data weren't enough to sway regulators, who in 2012 took issue with the drug's risk-benefit profile and demanded another trial. In the lead up to ridaforolimus' FDA rebuke, Merck paid Ariad roughly $200 million of a deal that could have reached about $708 million had everything gone according to plan. . . .


So Merck continues to hone its R&D commercialization focus. Getting out for around $200 million is actually a win, as that would have been perhaps a tenth of the amount needed, from here, to see Ridaforolimus through to commercialization, after new studies (if FDA would have ever granted approval -- and that was at best a dicey bet). And with that risk/benefit profile, sales would have been likely scarce -- if approved, at all. So it goes.

Merck's Former Infectious Disease Expert -- Carole Sable, MD -- Named Chief Science Officer Of SCYNEXIS, Inc.


As is often the case -- leading, researching, and doing at Merck, in a semi-supporting role, leads to being the boss, elsewhere. From Merck's perspective though, this is a precious form of talent drain -- a very high end version of the talent drain. These sort of human assets don't come along "every dang dynasty".

And yes, yet another Merckie has shown her stripes have earned her the Chief's seat -- and in this case, for a second time -- at yet another SECOND company. Before today's announcement, Dr. Sable was at one point the Chief Medical Officer of Novexel SA (since acquired by AstraZeneca). SCYNEXIS is lucky to have snagged a medical professional and researcher of this calibre. Well-done.

Quoting the SCYNEXIS release of this morning, then (BTW, that link is to the original French version -- here is the translation):

. . . .[Dr. Sable] brings to SCYNEXIS a significant tenure in the clinical development of infectious disease products, both as a clinician and in various corporate roles,” said Dr. Yves Ribeill, SCYNEXIS president and chief executive officer.

"We look forward to her contributions as we continue to advance our lead candidate, SCY-078, a novel oral and intravenous antifungal compound, as well as our anti-viral platform."

"SCY-078 represents a promising potential alternative for patients with invasive fungal infections who still experience significant morbidity and mortality despite antifungal treatment with currently available antifungal agents," commented Dr. Sable. "I am thrilled to be a part of SCYNEXIS’ experienced and dedicated team as we look to bring novel anti-infectives to patients in need."

Prior to her recent involvement with Merck & Co., Dr. Sable served as Chief Medical Officer of Novexel SA and President of Novexel Inc., the US subsidiary, where she was responsible for clinical development and successfully filed two INDs and successfully completed Phase 2b studies for two antibacterial programs which led to the acquisition of Novexel SA by AstraZeneca.

Previously, Dr. Sable was Executive Director of Infectious Disease and Vaccines Clinical Research at Merck & Co., Inc. where she was responsible for anti-bacterial, antifungal and vaccine development programs, including the clinical development of the antifungal agent Cancidas®. While with Merck, Dr. Sable also supervised the development and regulatory submissions for Invanz® and the in-licensing of the anti-infective amino-methylcycline PTK-0796 from Paratek Pharmaceuticals, as well as programs for sepsis, malaria, and anthrax.

Dr. Sable began her career as an Assistant Professor of Medicine and Infectious Diseases at the University of Virginia in Charlottesville. She received an MD from Jefferson Medical College in 1983 and completed an internal medicine residency and infectious disease fellowship at the University of Virginia. . . .


So -- it is likely that Dr. Permutter's return/arrival meant she was not going to be asked to be the chief at Merck, and that works out to be the rest of the anti-fungal and vaccine arena competitors' gain. And Dr. Sable's, too -- it would seem.

Monday, February 24, 2014

Not Sure How I Missed This. . . PEM-brolizumab Is The (Not So) New MK-3475 Name


Thanks go to an alert commenter on the back-up site. Clearly I hadn't been looking -- and I don't prescribe the stuff, even on an investigational basis, so I wouldn't "have gotten the memo, here." Heh.

Goofy me.

Apparently, back in November of 2013, Merck tired of its own previously clever and humorous naming of MK-3475. It switched the official chemical name from Lambrolizumab, to Pembrolizumab. Here's the bit -- and a link, again. However, I'll only correct entries from today, forward. I'm just. . . lazy. . . like that. [And similarly, this graphic (at right) will do, until I am around the laptop loaded with full-on Photoshop.]

. . . .This adoption statement (pembrolizumab) supersedes and replaces N13/06 (lambrolizumab), which is hereby rescinded. . . .


Once again, thanks to our readership. Love it!

UPDATING: Dr. Perlmutter Is Talking Almost EXCLUSIVELY About Anti-PD-1 Oncology Prospects


He is all about MK-3475, or pem-lam-brolizumab, at the moment. No slides to show, but maybe later he will begin outlining at least one of the second dip collaborations Merck has signed, this morning in Manhattan. He is likely also to discuss the FDA acceptance (regular review) of an BLA (the biologics equivalent of an NDA) for the next gen HPV vaccine candidate, called V-503, at MRL, at some point.

To be clear: he has repeatedly said that it is "too early to say" which company is in the lead -- in the Anti-PD-1 candidates' race, at the FDA's filing window.

I don't imagine that he'll discuss Merck's nascent Zen approach to IP problems, in India -- as that is not technically within his portfolio of responsibilities at Whitehouse Station. But one can hope. Here are the details; You are welcome to listen in to the web-cast.

. . . .Dr. Roger M. Perlmutter, president, Merck Research Laboratories, is scheduled to speak at the Citi 2014 Healthcare Conference in New York City on February 24, 2014 at 8:50 a.m. EST. Investors, analysts, members of the media and the general public are invited to join a live webcast of the presentation. . . .


In general, I expected -- and he is saying -- nothing Earth-shattering. And I do not expect a Consumer Health announcement of any kind -- or size, just yet. Not $6 billion; and certainly not $12 billion -- not just yet. Maybe toward the end of March 2014. In the meantime, be excellent to one another. [BTW, this is post No. 2,001 -- just since the merger was first announced. It is post No. 2,875 overall.]

Sunday, February 23, 2014

A Few General Observations -- And One Specific Class-Action Example -- About Historical Outside Sales At US Pharma Concerns


Back in November 2013, I said I'd likely not cover this dispute in great detail, pleading by pleading. That remains true. But some recent events have set me to thinking -- and as to the general questions raised by the suit, I feel a need to speak up. So bear with me.

Please note that the quotes in navy blue below are from attorneys not involved in this litigation. Please also note that I regard Merck as a very fair, and forward-thinking employer (here is Whitehouse Station's original answer to the complaint, in full -- a 19 page PDF). [Merck's amended and corrected answer, a 33 page affair, is here.]

I frankly cannot say the same (i.e., "fair and forward thinking"), about the former executive team at legacy Schering-Plough -- and I must also note that this suit was brought originally against legacy S-P, and largely targets its executives, for conduct occuring prior to Merck's arrival (circa 2006 to 2009). [So, once again -- should $250 million (or more) ultimately turn out to be "the bar tab" here -- it is (in my studied opinion) Fred, Tom, Tom, Brent and Carrie who skipped out on it, free and clear. And that group collectively got about $500 million (all in) in benefits and pay, for their trouble at S-P. Nice. Here is the plaintiffs' original putative class action complaint, a large 44 page PDF file.] The plaintiffs have recently amended their complaint, here -- making it a 71 page joint.

From the HR Exec article, remarking on the putative federal class action styled cause 13-2970 (US Dist. Ct., NJ) -- do go read it all, but here's a bit.
. . . .Nicholas Woodfield, principal of The Employment Law Group in Washington, has a unique perspective on the inner workings of such cases, as the firm he works for has been engaged in gender-discrimination cases against Fortune 500 companies around the United States. But, he says, he also has two sisters who were both pharmaceutical sales representatives and has gleaned knowledge from their experiences.

Historically, he says, such sales positions have been staffed primarily by women in an effort to gain access to busy – and typically male -- doctors.

"Not just women," he says, "but attractive women."

And Michael Pruitt, an employment-law attorney with Jackson White in Mesa, Ariz., has represented other pharmaceutical sales representatives in a class-action lawsuit before the U.S. Supreme Court, echoes Woodfield's assertion.

"The perception with Big Pharma," Pruitt says, "is that it employs many young females in 'outside sales' positions who meet directly with the doctors to answer questions and influence their prescription practices. But, beyond these positions, there is limited upward mobility for female employees."

And if pharma companies do indeed want young, attractive people pitching their wares to physicians, says Woodfield, then sending a visibly pregnant woman to pitch new medications to a male doctor "just isn’t as effective" a sales technique as sending a slender, non-pregnant sales rep would likely be.

This may be a cynical perspective, he acknowledges, and he emphasizes that it is his personal opinion, but "I think it’s a fair assessment of why you’re seeing this in this industry."

Importantly, Woodfield notes, those hired for these sales-rep roles must be as intelligent as they are attractive.

"It’s a complex business," he says, "and physicians are smart people."

Is it any wonder then that these individuals would want to also seek opportunities to move into more challenging, higher-paid roles after starting as sales reps?

"If the goal is to put attractive people before doctors and try to get their attention and, when they’re not as attractive, get rid of them, and if there are more women being hired, then you’ve got a situation where you’re probably going to be looking at more of these lawsuits in the future," says Woodfield. . . .


Having provided the readership with both the class's version of these events, above, and the successor company's version, here -- now twice (in each case, including my earlier backgrounder from November of 2013). . . we will likely fall silent on the topic, and let either settlement negotiations, or the federal district court determine the outcome. As a pharma veteran, I can also attest (to at least the historical) accuracy -- of Mr. Woodfield's observations in quite a number of instances above. I wish the plaintiffs all the best, as I suspect -- given the well-documented proclivities of former Schering-Plough management to skirt the law, generally -- where there is smoke. . . there is often. . . fire. [That link -- coupled to this one -- demonstrates that the ENHANCE delayed disclosure securities class action settlement was about 30 per cent higher than an ordinary "liars' discount" analysis would have predicted. Thus, those must have been some very ugly now-sealed Schering-Plough executives' depositions.]

Friday, February 21, 2014

UPDATING: Médecins Sans Frontières Criticizes Merck's "Zen" Raltegravir (Isentress®) License Deal With Cipla -- Not Likely To Be Cheap Enough


The French version of "Doctors Without Borders", called "Médecins Sans Frontières" (MSF) in the native tongue -- has registered strong condemnation of the Merck-Cipla "Zen" solution (to "nationalized" cheap access licenses) in India. MSF believes that the "authorized" generic structure of the deal still precludes other generic competitors from entering, and thus the deal will prevent robust price competition, they say. MSF is looking for 90 percent price cuts -- off of the $5,000 a year Isentress® (raltegravir) costs in country -- and MSF now implores the world to believe it when it says that won't happen without multiple generic launches. So, overnight here, it is urging the Indian ministry authorities to keep raltegravir on the list for consideration as a compelled license drug in India.

We shall have to wait and see, here. From pharmabiz.com, in India, then -- a bit -- but do go read it all:

. . . .The international medical humanitarian organisation Médecins Sans Frontières (MSF) has termed the license deal between the US pharmaceutical firm Merck Sharp & Dohme and Cipla for the HIV medicine raltegravir a ploy to prevent the Indian ministry of health from recommending a compulsory licence on this drug.

It appears that Merck is signing this deal to prevent the ministry of health from recommending a compulsory licence for public non-commercial use of raltegravir to the ministry of commerce, which would allow open generic competition on the drug. Raltegravir is on the list of patented drugs a committee constituted on compulsory licensing in the ministry of health is looking into. . . .

“The licence deal between Merck and Cipla is a huge disappointment because it does not allow for generic competition among multiple producers that could lead to the dramatic 90 per cent price decreases we’ve seen for other HIV medicines in India and other developing countries. India’s Ministry of Health should still pursue a compulsory licence on raltegravir to allow broad competition so that truly affordable generic versions of this drug are available to people across the developing world”, said Leena Menghaney, Campaign Coordinator, MSF Access Campaign, India. . . .


It will be interesting to see whether the ministry of health, and commerce officials keep Isentress on the list -- for study as a compulsory license drug. We will keep an eye on this, as you might imagine -- as it could easily be material to Merck, if the Indian authorities nationalize the drug, anyway -- in spite of what I've styled "the Zen compromise". [My backgrounder, here.]

Nuevolution's Big Win: Whitehouse Station Inks Second Collaboration In "Scandanavian Super-Speedy, Super-Scaled" Small Molecule Discovery Tech


I'll have more local color and analytical detail later today, but Merck signed what may well turn our to be a material research collaboration, overnight -- if it reads on/in oncology molecule/target discovery. The dollars are presumably tiny, by Merck standards -- but this little Scandanavian go go biotech shop now has deals with practically every one of the top seven pharma giants on the planet.

Yes, this Scandanavian tech is that promising. Nuevolution is a privately-held, venture backed sharp operator. [Honestly, and selfishly, I just wish it had ADRs, or any form of equity, trading here in the United States -- I'd be all over that, like white on rice.] Here's a bit from the presser -- but I will be back with more -- including the background on Merck's first investment here -- way back in June of 2008 (see that PDF, as background).

. . . .Nueveolution. . . announced that it has entered an exclusive license agreement with a subsidiary of Merck & Co., Inc., known as MSD outside the United States and Canada, for small molecule compounds targeting an undisclosed intracellular target for use as leads in Merck’s drug discovery and development.

Under terms of the agreement, Merck will gain exclusive rights for the further development and commercialization of the compounds. This is the second agreement between Nuevolution and Merck. Nuevolution will receive an undisclosed upfront payment and milestone payments for certain preclinical, clinical and agreed upon commercial milestones. In addition, Nuevolution is eligible to receive royalties on the commercial sales of approved products. Further financial details were not disclosed.

With this agreement, Nuevolution delivers on its new strategy to transform from a technology platform biotech company to a lead compound development company, providing novel products to improve future health treatments for patients. . . .


I promise you -- this is a company to watch -- and if you can get to the venture backers -- grab a stake. Drug candidates -- very promising ones -- are likely to be identified by the near-thousands, in only a few days, using this tech. . . Whoosh. [Trivial Sidecar Dept.: I'll also wager that no one else noticed that the company's logo is set in a non-italicized version of Baxter's proprietary typeface, right. Look closely. Baxter's ital version is trademarked. Hmmmm. . . .]


MRL's Dr. Roger Perlmutter To Present To Investors Monday Morning, In Manhattan: Citi 2014 HC Confab


I will have a second post up shortly, on this early snowy Friday morning, outlining at least one of the second dip collaborations Dr. Perlmutter may highlight, come Monday in Manhattan. He is likely also to discuss the FDA acceptance (regular review) of an BLA (the biologics equivalent of an NDA) for the next gen HPV vaccine candidate, called V-503, at MRL.

I don't imagine that he'll discuss Merck's nascent Zen approach to IP problems, in India -- as that is not technically within his portfolio of responsibilities at Whitehouse Station. But one can hope. Here are the details; I'll listen in to the web-cast.

. . . .Dr. Roger M. Perlmutter, president, Merck Research Laboratories, is scheduled to speak at the Citi 2014 Healthcare Conference in New York City on February 24, 2014 at 8:50 a.m. EST. Investors, analysts, members of the media and the general public are invited to join a live webcast of the presentation. . . .


In general, I expect nothing Earth-shattering. And I do not expect a Consumer Health announcement of any kind -- or size, just yet. Not $6 billion; and certainly not $12 billion -- not yet. In the meantime, be excellent to one another.

Thursday, February 20, 2014

Suvorexant -- Latest Comments, And Replies -- On My Other Back-Up Site: Timing Of Any FDA Approval


Over at my archive/back-up site, a long running, if sporatic, series of comments ask about progess on suvorexant, the Merck sleep aid candidate.

Here is my contribution to that:

. . . .Mr. Leder --

Two notes, as the author of this site. (1) Suvorexant isn't likely to gain approval until late 2014 at the earliest, as FDA has asked for data to support the theory that a very low dose (10 mg) would have a safe (no lasting morning impairment), yet therapeutic (soparific) effect. FDA has done so because it is concerned about the persistent morning impairment seen at higher doses, in the clinical trials. [Just as seen in other prescription sleep aids already on market in the US.]

(2) Last week, the US DEA listed a rule, for comment, which will become final -- and thus be the law, on suvorexant -- in 45 days. That rule makes suvorexant a schedule IV controlled substance. That means the DEA sees a very high potential for abuse of this drug, when it reaches market. Recreational drug users will try mightily to get a hold of 'scrips for the drug. So, it is going to be pretty difficult to get a 'scrip for it. Just so you are prepared for how things may shake out in late 2014, or early 2015. You -- and your treating medical doctor, or psychologist -- will be required to jump through some extra hoops in order to be able to get it to you -- and so that you may lawfully take it.

I am sorry, but that is how it is going to be.

I wish you the best. Sleeplessness can be agony. That I do understand.

Namaste

[Latest Commenter; some intervening comments redacted (for clarity of story line).:]

Submitted on 2014/02/20 at 1:54 am

Dear Ms. Wheeler,

just read ur insightful comments. I am suffering terribly from insomnia and, despite every possible " remedy", the problem has worsened. I'm praying that Suvorexant is the answer to our problem. Pls let me know the status of FDA approval -- if u are aware of the possible go ahead.

Most appreciatively,

-- Robert Leder. . . .

[Original comment:]

I have been following the approval process ever since I read about suvorexant. I am a 67 year old woman with no serious health issues, a cyclist and a gym enthusiast. However, after having suffered acute insomnia for over 20 years I am very eager to try this new medication. When I first read about it, I was very excited because it seemed as though it was being developed just for me.

I have been a patient at Stanford University in their sleep study program; ranked as one of the top sleep centers in the country. After three years of following their protocols my sleep did not improve at all and I was told that I had no underlying mental or physical issues which led me to believe insomnia was caused by some kind of chemical inbalance.

To read that this medication is going to affect my “awakeness” was such a revelation. That is what my insomnia has always felt like. I am always wakeful which makes it very hard to get to sleep and to stay asleep. Last night I was feeling fine, did not overeat, did not have any alcohol, and I didn’t sleep one minute.

My life and that of my family’s is so impacted by my condition. I don’t know how much damage it might have done to my overall health. I have tried many prescription pills which always loose their efficacy. I also have tried meditation, therapy, biofeedback and acupuncture. All these years later I am actually worse.

Keep me posted as to when this drug might be avilable.

-- Jacquelyn Wheeler

October 14, 2013 at 5:02 pm. . . .


We will keep you informed.

Breaking News In India: Merck Smartly Finds "A Zen Master's Third Path" In The Compulsory License Vs. IP Battles, On HIV Med Isentress® (Raltegravir)


I applaud Whitehouse Station's bold (and yet luminously Zen-like) move here. That comes first.

The Cipla deal just announced is a non-exclusive, in India. Thus, Merck will still be able to sell Isentress® to the richest Indians who are HIV+, directly. No middleman. [I suspect even they, though, will choose the much cheaper Cipla "authorized" generic.]

This is a smart business decision, given the current IP climate in India (see our backgrounders). Cipla will have to market Isentress under a different brand name -- to make it easily distiguishable from the genuine article out of Whitehouse Station. Cipla wins what it set out for, back in the Spring of 2011 -- the right to medicate AIDS patients in India more affordably; Merck doesn't surrender all the revenue, in country. Condor's Context®?: This may be the new model, for PhRMA members to avoid "compulsory license" imposition -- by courts, regulators & ministries, in country.

From India's BusinessWorld, overnight -- a bit -- but do go read it all:

. . . .[UPDATED: [In a]nnouncing the partnership, KG Ananthakrishnan, MD MSD India said, "We are proud to have entered into a strategic, India-specific partnership with Cipla. This partnership is aligned with our commitment towards patients in India and also addressing treatment challenges for high-risk patients by providing broader access to our innovative medicines and vaccines. It is a complementary partnership as MSD brings the research and scientific excellence for raltegravir, and Cipla brings their marketing excellence, significant reach among key clinician categories to drive product access". . . .]

Cipla will have a non-exclusive license to market, promote and distribute MSD’s raltegravir 400mg tablet, under a different brand name in India. Raltegravir is now approved in combination therapy in more than 76 countries for use in treatment-naïve adult patients with HIV-1 and in more than 114 countries for use in treatment-experienced adult patients with HIV-1.

Merck has a product patent for the drug in India since February 2008. The Chennai patent office had allowed the application filed in 2004. The US FDA allowed sale of this drug in 2007. . . . Global sales of the drug in 2012 were $1.5 billion, an 11 per cent increase over the previous year.

Interestingly, in April 2011, Cipla had moved an application to issue a compulsory license for the drug in India, citing the drug is overpriced and not affordable for Indian patients. . . .

"The deal demonstrates our commitment to working with partners globally who share the same pro access philosophy of Cipla. We want to ensure that all patients, particularly in developing countries, get access to the most innovative, breakthrough medicines available", said Subhanu Saxena, managing director and global CEO, Cipla.

The total number of people living with HIV/AIDS (PLHIV) in India is estimated at around 20.9 lakh in 2011. . . .


Again, for translational context, on the burden of AIDS in India -- a "lakh" is 100,000 of anything. That means there are 2.09 million people, living with HIV/AIDS, in India. (So that is over one fifth of all the people living. . . in Hungary, PhRMA! This is a very high burden malady -- in India.)

Even so, I am mindful of the billions Merck invested to create Isentress. And the company has already made a handsome profit on the admittedly life-saving drug, globally. This is the Zen master's answer to calls for nationalization of IP: find a third way. Well-done, Merck. Well done.

Wednesday, February 19, 2014

A Look Back -- And A Look Forward -- At Where Merck Global Health Innovation Fund, LLC Is Currently Investing Its $500 Million


This coming Saturday, at a Venture+ healthcare IT conference in Orlando, Florida -- Joseph Volpe, the head of Merck's Global Health Innovation Fund, LLC, will speak at a likely very lively panel session -- about how digital data initiatives are changing the face of health care delivery in the US, here in the second year of Obamacare.

While the fund was in 2010 staked with $500 million by Whitehouse Station, it technically is a separate LLC -- and in theory at least, is not directly required to follow the mothership's orders -- when investing. Even so -- it is wholly owned by Merck -- per the bottom of page 3 of Exhibit 21 of the latest SEC Form 10-K. So the LLC interests' are held by, and voted by someone, somewhere, inside the puzzle palace at Whitehouse Station. And those votes count for something -- so, Mother Merck is likely to reap the benefit of the winning investments -- from the portfolio (and more or less direct them, in the first place).

So. . . what is Joseph Volpe excited about? [And by implication, what is Merck excited about?] Let's listen in, via Healthcare IT News:

. . . .[Joseph] Volpe is speaking on a panel at the Venture+ Forum titled, "Health IT Venture Trends." And he says data – and all the capabilities related to it, from capture and storage to security to analytics – is one of the biggest trends he's paying attention to nowadays when looking for companies in which to invest.

"Data is the currency of the future," says Volpe. "And as that gets deeper and richer, we have to be able to do something with it."

Merck's Global Health Innovation Fund was spun off as a separate LLC from the pharmaceutical giant; its self-stated mission is "investing in transformative healthcare."

With some $500 million entrusted upon it to invest, Merck GHI has so far funded 22 companies since 2010, says Volpe – mostly minority positions, to the tune of $5 million to $15 million.

"We've broken it into two areas," he explains: "technology-enabled solutions and health IT platforms."

In the former space, "We look at precision medicine, accountable care, provider and patient engagement, decision support," says Volpe. The latter includes "health informatics, analytics, health data liberation" and more.

As the industry has evolved, Volpe has also noticed his investment priorities changing these past few years.

"We've gone from a high-level health IT focus to dig a little deeper," he says. "I'm looking now at privacy and security, predictive analytics, machine learning. . . ."


So -- the accountable care organization compliance bit lept out at me. That's going to be a hot set of properties -- especially if tied together, cohesively, by an upper-level Merck oversight/bundling initiative -- going into 2015. UPDATED: It turns out that the fund already sold off one of these venture investments -- called Humedica (with some longitudinal patient data sets, useful in accountable care tech) -- to United HealthGroup, a Minnesota based health insurer, in January 2013.

And, despite the conference literature's suggestion, we ought to assume that these areas are of keen interest to mother Merck, since the website for the fund sets it out this way: "Merck Global Health Innovation (GHI) invests in emerging companies that deliver breakthrough health care solutions, and which advance Merck's mission to discover, develop and provide innovative products and services that save and improve lives. . . ." Thus I'd look for some accountable care organization compliance tech -- to make its way into potential future Merck JV offerings, among other things.

More From The Caspofungin Acetate (I.V.) Generic Delay Wars -- Merck Sues AGAIN To Protect $620M In Cancidas® Annual Revenue


Well, as a Valentine's Day Card (albeit lacking all the usual hearts and flowers!), Merck filed suit on the Saint's day, in federal court in Delaware last Friday (the smallish complaint, as a PDF file here) -- against Xellia Pharmaceuticals, ApS -- to protect its Cancidas® interavenous antifungal franchise. That is the Merck branded name for caspofungin acetate, I.V. injectible -- as it is genericly known. And that is a reliable $620,000,000 stuffed into a few of Whitehouse Station's large black canvas duffel bags, every year. Okay -- some Condor Context® is again in order, here. So. . . here goes:

Back when I was very busy with other matters, circa early 2012, a fair bit of the Hatch-Waxman parts of the Cancidas patent suit history went unrecorded, here on my pages. So I have no links, as background, for the readers. To sum up, quickly though -- during late 2011 (Teva), and early 2012 (Sandoz), Merck settled two infringement suits (smallish PDF of a public record lawyers' letter) that it had earlier brought under the Hatch Waxman 30 month stay provisions, to keep generic versions of Cancidas off the market. While the so-called '300 patent was set to expire (before evergreening amendments, and provisional-updatings) in late 2012, there is still no generic on market in the US, to my knowledge.

The federal court records indicate that Merck settled with both Teva and Sandoz -- and it would seem to the casual observer that the length of time each agreed to stay off market with a generic exceeded the original '300 patent's life. So it is fair to allege that these were pay for delay settlements -- costing the US consumers and insurers perhaps $375 million a year (the reduction in pricing/margin likely from a generic entrant).

So, against that historical background -- two suits; two settlements (with terms held in confidence) -- we just learned that Merck has sued Xellia to keep it of the market for the Hatch-Waxman 30 month stay period. Thus, as even the ultra-conservative Dan Troy (then FDA's Chief Counsel) testified in 2003, when he was running FDA's legal shop:

. . . .Under FDA’s traditional interpretation of the Hatch-Waxman Amendments, multiple 30-month stays have been possible. Submission of newly issued patents after an ANDA application has been filed with FDA has required the appropriate certification and notice to the NDA holder and patent owner with the possibility of a 30-month stay if patent infringement litigation resulted. As a result, there have been a number of instances where there has been more than a single 30-month stay. These include paroxetine hydrochloride (Paxil) and gabapentin (Neurontin).

A recent review of FDA’s records indicates that of the 442 active ANDAs that contained paragraph IV certifications, only 17 have had multiple 30-month stays, representing 3.8 percent of all applications with patent challenges. However, we note that a significant number of these products have high dollar value annual sales, and we are aware of some instances where multiple stays have resulted in the delay of a generic drug approval for a number of years. . . .

Greater access to generic drugs will reduce health care costs because the price of generic drugs is typically much lower than the brand-name drug. Reducing expensive lawsuits over drug patents and making the approval process more efficient will also help to lower national health care costs by reducing the cost of bringing safe and effective generic drugs to market. . . .


The journey of Merck's Cancidas is in many respects like that of Paxil® and Neurontin® -- both impliedly criticized by then-FDA Chief Counsel Dan Troy. So -- Condor's Context? Buying off would-be competitors with secret settlements -- is the stuff of Sherman and Clayton Act claims, right? Right, but for the gerry-mandering of timelines, in FDA interference procedings. Even so, FTC has the right to subpoena or request those settlement agreements to make sure they are not collusive, or unduly injurious to otherwise lawful price competition.

And yet, here we are again -- over a decade later -- still seeing multiple shenanigan-laden paths to lengthening patents, and keeping the prices paid by US consumers (and/or their insurers) very high. We will follow this one herafter with a jaundiced eye. Be forewarned, dear readers. [I just think it's. . . mean. . . to bring suit on Valentie's Day, afterall. For shame, Merckies. Heh.]

Tuesday, February 18, 2014

Apparently, Novartis Is Trying To "Buy Itself A Horse" To Enter The Anti-PD-1 Oncology Races -- Thank-Yous Go Out To My Commenters


Again -- my ever-watchful, vigilant and cogent anonymous commenters have provided a nice story idea -- on an otherwise slow Merck news day.

This time, it seems Novartis has belatedly realized what a boon an effective Anti-Programmed (T-Cell) Death Receptor-1 monoclonal antibody would be, in solid organ tumors -- albeit almost at post-time. So, the euro-giant is apparently buying Boston based CoStim Pharmaceuticals (an entrepreneurial little wunderkind), to effectively get at least some horse(s) into this race. [Roche has one too.] Clearly though, none of those companies' progams are at Phase III yet. So our earlier predictions stand, for now: while Merck may get approval for melanoma first, the bulk of the revenue will be in lung and kidney cancers -- and there I have BMS out ahead with later-stage, better data.

So. . . I still think BMS gets two-thirds of the pie, and Merck gets one-third of it, come mid-2015. But it is a perhaps $25 billion a year pie. And now Novartis may nip about five percent of that, off of these two -- if and when its acquired PD-1 candidates reach market. Not that those two will even notice (much) though, because a realistic estimate puts Novartis at a 2017 or 2018 launch date -- in all probability. Here is our comment-box discussion (slightly cleaned up for typos, from yesterday at lunch):

. . . .Anonymous said. . .

Pardon the interruption here, Condor, but another player has entered the PD-1 game. Interesting take in this write up, on where Merck's horse is in the race as well.

February 17, 2014 at 8:45 AM

Condor said. . .

Thank you so much Anon.!

That is interesting. I find it fascinating that Novartis is trying to buy a ticket to/horse in this show.

It is clearly now too late to make one, from scratch.

I also think basing a determination of "leading" -- in the race to market [the article guesses that Merck's lambrolizumab has the lead, given the rolling FDA submission announcement, of early 2014] -- on a rolling FDA submission. . .

. . .is a little unsophisticated.

BMS is likely to have better data in the "bigger burden" cancers, and sooner than Merck will -- and the bigger impact cancers (not just late stage melanoma). . . will drive the market win.

If oncologists will readily and lustily write "off-label", based on an initial clearance/label for melanoma, at FDA -- well, Merck may garner at least a temporary lead (should it actually be the first to clear FDA with a melanoma label) -- but the real question is whether the insurers, exchanges (and Tricare) will pay top dollar for "off-label" prescriptions in solid tumor cancers, like lung or kidney.

I am skeptical about that, so the winner will LIKELY be the one who gets "on label" in lung and solid organ cancers first.

We shall see.

Do stop back! Namaste

February 17, 2014 at 12:16 PM. . . .


As I say -- it will be an entertaining race, once the (latest version of a) starter's bugle sounds -- during the last weekend of May, at the 2014 ASCO conference -- in Chicago's South Loop. I'll pop over for that, now, for certain. Much more actual Phase I/II/III data due -- on all these thoroughbred candidates, then.

Monday, February 17, 2014

A Book I'll Certainly Read, Come April -- India Vs. Pharma IP Redux


As a follow-up to my longish entry of last night, regarding the increasingly shrill rhetoric -- on both sides of the globe -- about IP rights v. access to life-saving medicines at a "living, affordable" cost to the patient, I thought I'd mention this forthcoming book, by a pair of law professors -- one from Canada, the other from Israel.

I will pick it up, when it is printed, in April 2014. It looks to nicely distill much of what resides at the center of the current India debate I'm covering, here. Here's a bit of the tease for it -- out of the Cambridge University Press site:

. . . .Does health care promote equality, or does it in fact advance the opposite result?

Does inserting the idea of “the right to health” into health systems allow the reinsertion of public values into systems that are undergoing privatization? [Condor counters: I might suggest that no one (i.e., no government) "inserts" basic human rights -- they exist, whether we acknowledge them, or not -- but I take the general point as well-made.]

Or does it allow for private claims to be rearticulated as “rights,” in a way that actually reinforces inequality?

This volume includes studies from countries such as the United States, the United Kingdom, Brazil, Canada, The Netherlands, China, and Nigeria, among many others, as well as authors with expertise regarding both the legal and health systems of their countries. . . allow[ing] readers to see the differing role of rights in various health systems. . . .

[Chapter 16] Right to health in India: addressing inequities through litigation | Anand Grover, Maitreyi Misra and Lubhyathi Rangarajan. . . .


This is, quite honestly, why there are no easy answers (in my estimation), to the titanic wrestling match between India and big pharma, now underway. We will promise only to keep (1) an open mind, and (2) offering small-window insights -- from time to time -- but be assured, you will read a lot more about this in 2014, and beyond.

And well-beyond India, too -- into all the BRIC geographies. . . that much is certain. With the richest nation on Earth finally recognizing a basic right to health care for all of her citizens (under Obamacare -- where at least her more-rational Governors are so proceeding) -- there is sure to be a "revolution of rising expectations," in the emerging economies as well.


[Finally, at the risk of sounding erh. . . shrill. . . I must return to that year end PhRMA press release -- to offer some advice on constructing more rational arguments -- for next time around: "When one compares the economy of an entire country (Hungary) -- to a single city (Mumbai) -- but ignores 1.23 billion additional human beings -- one has ALREADY lost the argument."]

Be excellent to one another.

Sunday, February 16, 2014

Congrats to Ed Silverman! Joining the "Capitalists' Paper Of Record!" Nice!


This one updates my early January piece, on this topic.

The PharmaGuy is reporting that my buddy Ed has joined (gasp!) the blog-corps of The Wall Street Journal. I'll never bedgrugde anyone their steady paycheck -- afterall, he has a family to take care of. . .

And I know for certain that Ed will be as fiercely independent as he's ever been, regardless of the masthead under which he writes. Here's Pharma Marketing Blog's perspective on it (one I don't necessarily share, despite liking the PharmaGuy):
. . . .Will there be the same slow and subtle change in Silverman's investigative journalistic style to match the drivel that currently is published on the WSJ Health Blog? By which I mean, will we see posts like "Six Tips For Better Napping" rather than the exposés for which Ed was famous?

I hope not.

But one thing seems certain: Pharmalot is definitely dead this time. . . .


All I'll say is that nothing lasts. . . forever. Personally, I think Pharmalot's not really dead -- it's only mostly dead. In fact, it's only been mostly-dead since January 1, 2014 (that means at least nine more months until Ed sees his shadow, again!).'Nuff said.