Friday, March 05, 2010

Deals of the Week Meditates on Medivation's Medication

We dare you to say the phrase three times fast. Can’t do it? Maybe you should switch to Russian. Google translator not working? Try this simple phrase instead: Блин!

All kidding and alliteration aside, that was likely Pfizer’s reaction this week after the big pharma and its biotech partner announced two Phase III trials of the highly anticipated Alzheimer’s treatment dimebon failed to meet either of their primary endpoints.

The news had tongues wagging, and not just because this is yet another high profile late stage failure Pfizer can ill afford. Dimebon is a decades-old allergy drug that appeared to work in Alzheimer's by some unknown mechanism. The skeptics' chorus began in July 2008, when Medivation published stunning Phase II/III data showing drug-treated patients did significantly better than placebo-treated patients when assessed using standard neuropsychiatric evaluations. But that study comprised just 183 patients and was conducted in just one country, giving new meaning to the phrase “from Russia with love." Certainly Medivation loved the data; just two months after it published its study, the biotech inked a lucrative partnership with Pfizer worth $225 million up-front.

But this week we learned anew how alliance-driven love is a many-splintered thing. Medivation’s stock is down 70%, last we checked. And Pfizer has lost a chance to extend its Alzheimer’s franchise beyond Aricept, which goes generic at the end of this year.

We can't help but wonder what it all means for biotechs with unpartnered Alzheimer’s programs. Dimebon is far from the first to go belly-up after apparently successful Phase II data. (Remember Myriad Genetics’ Flurizan?) That’s bad news for companies such as Allon Therapeutics and Prana Biotechnology, which have Phase II meds in need of deeper-pocketed developers. Indeed, as big pharmas pledge their desire to play in this most lucrative CNS space, we won't be surprised if more go for financing strategies a la Lilly’s 2008 deal with TPG and Quintiles. At the very least, we expect upfront values to decline and more emphasis on milestone driven terms. (Not that this wasn’t happening anyway, especially for later stage assets.)

Which brings us to the end of our meditation on Medivation. Omm. If we have one piece of advice for Kristin Peck, the new SVP of business development at Pfizer, it would be to practice this mantra: Option-based deals. Option-based deals. Option-based deals. Ahh. Isn't that better?

As you watch your thoughts float by like clouds, please remember, there is no you or me, there is only...

Watson/Columbia Laboratories & Watson/Population Council: Watson announced a pair of deals this week to bolster its branded women’s health care products line, purchasing Columbia Laboratories’ marketed infertility drug, Crinone/Prochieve, and Population Council’s Phase III contraceptive vaginal ring. Watson will pay an upfront fee of $47 million in exchange for 11.2 million newly issued shares in Columbia and U.S. rights to Crinone/Prochieve, which pulls in about $20 million in annual sales. But the real opportunity for the infertility therapy is the prevention of preterm birth. Here Columbia will continue to lead development of the product (it’s in Phase III), but its costs are capped, with Watson picking up the tab if expenses exceed an undisclosed limit. Watson will also pay $45.5 million in clinical and regulatory milestones in this new indication. Financial details of Watson’s second tie-up of the week were undisclosed but apparently include the usual upfront, regulatory and sales milestones, and royalties. While both deals provide Watson’s 350-person sales force with additional branded products to sell, it’s worth remembering that the drug maker’s overall business is still primarily focused on generic offerings, which last year generated $2.3 billion in revenue. Still, in an interview with “The Pink Sheet” DAILY, CEO Paul Bisaro argues his company has made great strides in the branded market, noting the firm is on the verge of providing an array of women’s products, including a novel oral contraceptive and an emergency contraceptive currently under review at FDA.

Astellas/OSI Pharmaceuticals: On Mar. 1 Astellas launched a hostile $3.5 billion, $52-a-share bid for OSI Pharmaceuticals to grab part of the growing revenues of lung- and pancreatic-cancer treatment Tarceva. Astellas made a relatively modest U.S. oncology-focused purchase when it bought the Santa Monica, Calif. antibody R&D shop Agensys for $537 million in 2007, but it would love a larger commercial footprint in the U.S. similar to what its Japanese peers Takeda Pharmaceutical and Eisai have bought in recent years with their Millennium Pharmaceuticals and MGI Pharma deals, respectively. But at least one major OSI shareholder says not so fast, $60 a share is fair price, likely emboldened by the fact that during the year-long unsuccessful wooing of OSI management, Astellas kept suggesting a $55-to-$57 range. Not surprisingly, OSI's share price has traded all week between $56 and $57. Funny, that. The situation bears some resemblance to Astellas's $1 billion hostile bid for CV Therapeutics last year: a 40% premium, a lawsuit to prevent a poison pill, and a threat of a proxy fight. But Gilead Sciences rode in with a $1.4 billion topper and Astellas quickly backed away. This time, will OSI partner Roche play the white knight? Does it have to? After all, it already keeps 80% of ex-U.S. sales of Tarceva, and its U.S. arm Genentech co-promotes Tarceva stateside. Stay tuned, Astellas's tender offer ends Mar. 31. -- Alex Lash

Bausch & Lomb/NicOX: In August 2009, when NicOx took back full rights to its Phase II glaucoma drug NCX116, it promised investors to have a partner for the program in 2010. This week, the company made good, announcing an alliance with Bausch & Lomb. Since being taken private by private equity firm Warburg Pincus in 2007, B&L has been quietly rebuilding primarily by acquisitions or alliances that target innovative products. Interesting deals include the firm’s 2008 take-out of intraocular lens player eyeonics and alliances with the likes of Pfizer, Croma Pharma and Tubilux Pharma. Still the upfront value B&L is paying NicOx -- just $10 million for a Phase III-ready program -- suggests wariness. (Milestones up the potential deal value significantly to $170 million.) Thetrepidation is probably warranted. Recall that Pfizer lost interest in the program because mid-stage trials suggested modest clinical benefit at best compared to Pfizer's juggernaut Xalatan. That’s relevant because Xalatan will soon go generic; in the current payer-dominated environment, pricy new glaucoma medicines will have to show much better results in the clinic to warrant coverage by managed care plans.

Shionogi/QuatRx: Shionogi's U.S. subsidiary, Shionogi Pharma (formerly Sciele Pharma), acquired global development and marketing rights to QuatRx Pharmaceuticals' selective estrogen receptor modulator ospemifene, building on the company's sexual medicine and women's health portfolio. Shionogi Pharma will pay $25 million upfront and up to $100 million in milestone payments, and it expects to file a U.S. NDA in the second half of 2010 for the treatment of postmenopausal vulvovaginal atrophy. If approved, the once-daily tablet would be the first non-estrogen treatment option for vaginal atrophy; SERMs that are currently marketed in the U.S. have not shown beneficial effect for vaginal atrophy symptoms. QuatRx posted positive Phase III results in January 2008, announcing statistically significant results for all primary endpoints in its first Phase III study. At the time, the company planned to market the product on its own in the U.S. and partner elsewhere. -- Daniel Poppy

Merck KGaA/Millipore: There’s life in the tools sector yet. After disappointing investors with lackluster 2009 financial results, Merck KGaA put its own spin on diversification with a proposed acquisition of Massachusetts-based Millipore for €5.3 billion (US$7.2 billion). The addition of Millipore, which had interest from a number of suitors, adds $1.7 billion in sales to Merck KGaA's coffers and bulks up its chemicals division, which will now be responsible for an estimated 35% of the German firm’s revenues. But the move surprised analysts, in part because it was Merck's non-pharma divisions -- life-science chemicals and liquid crystals -- that had a poor 2009, dragging down overall revenues. However, the acquisition may add the benefit of much-needed biologics manufacturing expertise. Merck's therapeutic cancer vaccine, Stimuvax , is in Phase III clinical trials, and its recombinant protein atacicept is in Phase II/III trials for autoimmune disease. -- John Davis

GlaxoSmithKline/Abbott: As part of an ongoing collaboration, the companies said Mar. 3 that Abbott is developing a molecular test for selecting patients with melanoma who could benefit from GSK’s therapeutic vaccine targeting the MAGE-A3 antigen, which is expressed on melanoma cells but not normal cells. Last July, GSK engaged Abbott to develop a test for the first product expected out of its Antigen Specific Cancer Immunotherapy (ASCI) program: a diagnostic to select patients for its MAGE-A3 ASCI vaccine for non-small-cell lung cancer (NSCLC). MAGE-A3 ASCI is in Phase III trials in both melanoma and NSCLC. The latter study is more advanced, with enrollment slated for completion in 2011. Abbott will have to run separate trials to clinically validate its molecular test for the melanoma indication, and while the target is the same, there may be differences in sample prep because it is assaying a different tumor type. That said, the new development likely says more about GSK’s goals in immunotherapy than Abbott’s already-established skills as a companion diagnostics partner. As we chronicled last summer in IN VIVO, GSK’s immunotherapy program will span almost two decades before an anticipated first approval. Clearly, GSK wants to be comfortably armed with trial data using a validated companion diagnostic when it goes for approval, perhaps having used the Abbott screening test to identify a subset of patients with a sufficiently high delay in time to relapse. -- Mark Ratner

AstraZeneca/Merck: This week AZ officially swung the R&D axe and cut staff in 10 specific disease areas, including depression and anxiety, hepatitis C, acid reflux, and thrombosis. But it's still spending cash on cardio. AZ announced Mar. 1 it would payMerck $647 million to regain full rights to a group of drugs, including marketed hypertension medicines Atacand, Lexxel, and Plendil, plus the potential blockbuster Brilinta currently under review by the FDA and the EMA. Ties between the two big pharmas go back to 1982 when AZ predecessor Astra teamed up with Merck to co-develop and co-market several drugs in the U.S. Astra bought out Merck’s 50% ownership of the joint venture in 1998, setting up a series of option dates on which Astra -- or its successors -- could regain full rights. Thanks to this deal, AZ now owns all products from the JV except those related to the purple pill franchise Nexium and Prilosec. (Those meds are part of a second option agreement which can be exercised as soon as 2012.) Of the marketed products now wholly owned by AZ, only Atacand can truly be considered a blockbuster, with more than $1.4 billion in worldwide sales in 2009. Much of the deal was almost certainly driven by a desire to own full rights to Brilinta, which posted superior results to Sanofi/Bristol’s Plavix in an 18,000-patient trial in November 2009. According to Cowen and Company analyst Steve Scala, Brilinta if approved could generate annual sales of $600 million in 2012 and $1.5 billion in 2015.

Merck/GTX: As we noted in an earlier post this week, sometimes the bear really does get you.

Image courtesy of flickrer connerdowney used with permission through a creative commons license.


zuppy said...

It is not only Russian studies you have to cast a cold eye upon. What about the Edward Tobinick Studies
Not bad for a Los Angeles dermatologist with a practice he calls Institute of Laser Medicine which also doubles as Institute for Neurological Research. Alzheimer's, Disc-related disease, metastatic Cancer, SARS, no problem. Tobinick has managed to make extraordinary claims in the off-label use of an anti-TNF biologic therapy for rheumatoid arthritis - etanercept (Enbrel) for all these chronic conditions and some more, but it does not stop there. Tobinick claims to have invented two unique procedures (which he claims patent rights) in the novel administration of his treatment. Has Tobinick over these last ten years ever provided one piece of data for independent scrutiny; the answer is NO! While you digest these facts, there are Alzheimer's families seeking out Tobinick at his clinics, there are Alzheimer's families seeking out Medical Doctors, who have signed up with Tobinick, and for a fee and royalty, provide 'The Tobinick Method' off-label etanercept (Enbrel)administration to desperate Alzheimer's patients. If you want a medical ponzi scheme, I volunteer Tobinick's Alzheimer's claims. Let me guide you to Tobinick's pre Alzheimer's claims, when he put all his talent with off-label use of etanercept (Enbrel) for disc-related disease, which he patented as 'DiskCure' . Tobinick early on, learned the persusive qualities of creating his own 'testimonial videos' depicting 'real life' people and their experiences after Tobinick's etanercept treatment. This real 'testimonial video' is one of my favorites.
The title: Video 7: Rapid relief for an orthopedic surgeon following the patented perispinal etanercept treatment at the INR.

Tobinick created video claims this is an Orthopedic Surgeon......this is beyond absurdity.

Anonymous said...

Today April 13, 2010 in the online open access Journal of Neuroinflammation, a milestone was passed when the Number 1 most accessed article passed the 80,000 threshold, namely: Case report
Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration
Edward L Tobinick, Hyman Gross
Journal of Neuroinflammation 2008, 5:2 (9 January 2008)

This has to go down as a day of infamy in the annals of Alzheimer's research, when a dermatologist claims 80,000 accesses for a spurious article.

Journal of Neuroinflammation Top 10 most accessed articles for last 30 days / past year / all time


Case report
Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration
Edward L Tobinick, Hyman Gross
Journal of Neuroinflammation 2008, 5:2 (9 January 2008)
[Abstract] [Full Text] [PDF] [PubMed] [Related articles] [F1000 Biology] [Cited on BioMed Central]

36494 Commentary
Perispinal etanercept: Potential as an Alzheimer therapeutic
W Sue T Griffin
Journal of Neuroinflammation 2008, 5:3 (10 January 2008)
[Abstract] [Full Text] [PDF] [PubMed] [Related articles] [Cited on BioMed Central]

zuppy said...

OXYMORON - Expert Review of Neurotherapeutics - published a creation by Edward Tobinick Dermatologist
On the Alzheimer’s topic. Can I guide the readership to this brand new OXYMORON : Expert Review of Neurotherapeutics (June 2010 edition) after internal peer-review - made the decision to publish
[ Perispinal etanercept: a new therapeutic paradigm in neurology ] author Edward Tobinick

Expert Review of Neurotherapeutics, June 2010, Vol. 10, No. 6, Pages 985-1002.

Edward Tobinick Affiliations:
David Geffen School of Medicine at UCLA, 100 UCLA Medical Plaza, Suites 205–210, Los Angeles, CA 90095, USA.

On reading Edward Tobinick affiliations that accompany this paper; Where does Edward Tobinick work and what are his clinical qualifications. Write them down and then compare with what you find in these links!

NOW, Who is the Moron! eh ‘EXPERTS’ at Expert Review of Neurotherapeutics
Expand full comment

zuppy said...

Follow on Teaser on Edward Tobinick the Dermatologist
Follow on Teaser: Open Link and click on Video 7. After viewing it, I invite you to cast your vote in ‘THE POLL: Orthopedic Surgeon attends Tobinick the Dermatologist for ‘DiskCure’ - off label etanercept (Enbrel)

Open this link and click on Video 7

Video 7: Rapid relief for an orthopedic surgeon following the patented perispinal etanercept treatment at the INR.