AZ's Payer Push No Help to Brilique in France

These days, you've got to schmooze with the payers as well as the regulators. AstraZeneca knows that; it has indeed been playing up its payer-focused strategy, with recent declarations of its bid to become "the number one company in terms of payer interactions," according to top AZ dealmaker Shaun Grady.

So it should have known that just because clot-buster Brilique was approved by the European authorities in December 2010, that wasn't the end of the story. And indeed, the French health technology assessment agency, known as the Transparency Commission, following a Jan. 19 review meeting, rejected the drug for reimbursement/pricing discussions. Hence AZ withdrew its submission.

The agency is concerned about the drug's side-effect profile, and was also influenced by FDA's lukewarm response to AZ's application for approval in the U.S.: FDA in December sent the company a complete response letter questioning the drug's efficacy in U.S. patients.

Fair enough; after all, the drug didn't seem to work among the U.S. cohort of AZ's 19,000-patient, multi-national Phase III trial. There are all sorts of discussions ongoing as to whether it's because the U.S. patients were on higher aspirin than those in other countries. According to AZ, the French want to see additional information, including clinical data contained within the company's response to the CRL, which was submitted on Jan. 21. (In other words, too late for the French meeting).

Anyway, the moral is that payers are likely to jump on concerns raised by any approval agency, even those outside their own territories. (We don't suspect France's concerns are anything to do with the fact that the genericizing competitor drug Plavix is ... well, French.)

It's tough luck for AZ, though, despite its best intentions (..."we're meeting payers' needs for value-based product differentiation by improving our ability to assess clinical and economic outcomes in real-world populations (as an example, earlier this year we announced a new outcomes study we were kicking off for Brilinta) declared an AZ spokesperson earlier this year).

France accounts for nearly a third of the market share for anti-platelet drugs in Europe, according to Sanford Bernstein analyst Tim Anderson. And AZ needs Brilique it faces expiries for Nexium and Seroquel. It also needs the drug to start generating revenues fast, because Plavix is either going or gone off patent.

AZ says it plans to supplement the Brilique reimbursement dossier and plans to resubmit to France's Transparency Commission within the coming months. Hopefully for it, the French set-back won't give FDA, set to rule by July 20, any further concerns. Anderson suggests in a March 23 note that "the odds of a negative ruling would seem to increase at least slightly."

Zut alors.

Update: AZ has corrected us on a couple of technicalities: The Transparency Commission didn't actually reject Brilique, they asked for additional information, and AZ withdrew its submission. Similarly, FDA wasn't questioning the drug's efficacy in U.S. patients, it was requesting additional analyses with respect to those patients. Sorry.

At Afssaps, Two Heads Apparently Better Than One

Whilst countries in the Middle East struggle with the concept of the democratic process, the French minister of health, Xavier Bertrand, is seeking to hand pick the next head of the national medicines agency, Afssaps.

His choice — in fact his second, as the appointment of Hubert Allemand, deputy head of the national insurance system, failed for some unsubstantiated reason — is Dominique Maraninchi, president of the National Cancer Institute (INCA). Bertrand hopes that the appointment, arising as a result of the Mediator scandal, will be rubber-stamped by parliament in a matter of days.

Maraninchi is likely to be only one visage of the double-headed eagle that health minister Xavier Betrand wants to place at the pinnacle of Afssaps. Bertrand is looking to divide responsibilities at the agency between a medical person — arise Maraninchi — and an administrator.

Upon his somewhat unwarranted, yet dishonorable, discharge from the post of Director General at Afssaps — he effectively resigned under pressure — Jean Marimbert set down three goals, the fulfillment of which would re-establish public confidence in the medicines agency: improved pharmacovigilance; increased transparency; and the abolition of conflicts of interest. The question is whether Maraninchi has the determination, the ambition and the credibility to pursue these aims.

Aged 61, Maraninchi has been involved in the fight against cancer for over 30 years, having co-authored in excess of 275 articles, founded a pilot unit for bone marrow transplant in the Paoli-Calmette Institute in 1981 and established a pilot unit for research into treatment with cytokines and immunotherapy techniques at the same instate in 1988. He was appointed Director of the institute in 1990, President of the National Centres for the Fight against Cancer from 2002-2004, permanent advisor to the interministerial mission for the fight against cancer in 2003 and President of the National Institute for Cancer in July 2004.

Whilst nobody can argue about Maraninchi’s impressive pedigree in the field of cancer, there is only limited evidence to suggest that he will be able successfully to nurse an ailing Afssaps back to health. Maraninchi has understandably limited experience of pharmacovigilance, having led an institute that predominantly looks for cures and not faults. Pharmacovigilance is unlikely to fall under the auspices of the next administrator, and therefore there appears to be a slight gap in Bertrand’s plans for Afssaps. Presumably he either expects Maraninchi to learn on the job, or to rely on the expertise of his staff.

Maraninchi is well-known for expressing the view that transparency and the effective provision of medical care go hand in hand. At a meeting organized by the Socialist MP, Gérard Bapt, president of the group for the study of environmental health at France’s National Assembly — the lower house of parliament — Maraninchi, at the time president of the national cancer institute, commented on the benefit of opening up the institute’s advisory bodies to include public health interest groups. It is likely, therefore, that he will pass the health ministry’s transparency test.

The issue that is perhaps likely to catch the imagination of the general public, however, is that of conflict of interest. Media reports highlighting potential links between the government and Servier have incensed the public. More recently, at a grilling of the Afssaps hierarchy at the National Assembly, one deputy took particular satisfaction in pointing to connections between Philippe Lechat, director of medicines evaluation at Afssaps, and Servier.

The connection was tentative at best, with Lechat only taking part in the past in administering clinical trials involving a couple of the companies’ products. However, in turbulent times such as these, the public interprets a relationship between doctors and drug manufacturers as being on a par with the pact between Faust and the devil.

What then, will the media make of a similar link between the esteemed — and, to quote the French media, charming — Maraninchi and both GSK and Roche, particularly in the event of a new health scandal? It appears that Bertrand is banking on the fact that Maraninchi’s medical pedigree — in contrast with Marimbert’s background as a civil servant — will inspire enough confidence to quash public concerns.