The Big Red Biotech Blog

Merck Less Bullish on Biosimilars?

Merck BioVentures, the biosimilars endeavor set up by Merck & Co. in late 2008, is being subsumed into the biologics and vaccines division of Merck Research Laboratories. Mike Kamarck, who has led BioVentures since 2010, has left the company.

The IN VIVO Blog: Merck Says Goodbye to Independent Biosimilars Unit.

Biosimilars may indeed be a new kind of innovation, one that brand-focused biologics companies would be foolish to discount and one that many seem to be tripping over themselves to embrace (see Amgen/Watson, Baxter/Momenta, Biogen/Samsung).

Merck's move to reduce its BioVentures group at least in stature seems to raise doubts on its attitudes toward biosimilars and is at odds with the bullish attitude of groups like Novartis' Sandoz unit, which just this week predicted incredible growth for its own biosimilars business. That said, it’s hard to say whether this retrenchment will be part of the long-term learning process or bigger strategic shift, as the whole field is in the midst of an evolution and successful business models have yet to fully materialize.

Posted by Bruce Lehr Apr 27th 2012.

BIO Voices its Comments on Biosimilars to FDA

BIO's response to proposed FDA guidelines is covered nicely in the Patent Docs blog. 

BIO asks FDA to publish specific statistics and/or ranges acceptable  for a determination of biosimilarity following the European model. BIO advocates for a more extensive clinical trial requirement to establish biosimilarity, including animal toxicity and human clinical trials. BIO also suggests a "cautious approach" to the extrapolation of data to other indications and patient populations without trials. BIO also asks for prominent labeling of the biosimilar to highight differences in route of adminsitration, presentations and conditions of use (presumably will inhibit switching) between biosimilar and reference product.

BIO also had comments related to quality and access to confidential information. On the quality front, BIO aks that any intentional differences from the biosimilar in host cell type, primary structure, formulation, or immediate package from the reference product result in immediate need to follow the BLA pathway and not ABLA.  BIO cites patient safety as the reason for this standard.

BIO requested explicit acknowledgement from the FDA that certain information within the reference BLA, including manufacturing facilities, be treated as confidential (see Abbott response to FDA in earlier blog post).  BIO disfavors comparison of a biosimilar to a non-US licensed product but wants to be particularly protective of manufacturing information in this instance. Trade secrets from all BLA must be protected from disclosure in biosimilar application process. The ABLA must stand on its own merit, supplemented with only public information.

In general, BIO suggests changes that will make it more difficult to gain ABLA (abbreviated biosimilar) approval.  These would appear to enhance patient safety and to also protect the competitive advantage of its BLA holder members.

Posted by Bruce Lehr Apr 26th 2012

New Drugs -- If You Can't Make 'Em, Buy 'Em

That seems to be the current motto of many big pharma companies and describes their relationship to biotechs.  But if you go that route, you will pay handsomely.  Fierce Biotech reports (via Bloomberg) that pharma companies are forking over on average a 71% premium in picking up new biotechs (worth > $500 M) for their pipelines.  This is reportdly the highest premium since 2000. 

So if you read the previous post about "bad culture" in Big Pharma, another cost (beyond poor R&D productivity) seems to be having to pay the piper when it comes to buying from the biotechs. Cutting the R&D budget likely won't help rectify that -- although it may help fund it a bit. 

Supply and demand is taking over and the acquisition prices will keep rising as a result in the short term.

Posted by Bruce Lehr Apr 25th 2012.

Pharma R&D Follies

Here's a couple of links to blog posts outlining possible reasons that Big Pharma R&D is experiencing such a low return in bringing new products to market --- especially over the last 10 years.  One factor that is discussed is -- CULTURE (see Life Sci VC and In the Pipeline). 

The basic premise?  

Fundamentally, I think the bulk of the last decade’s productivity decline is attributable to a culture problem. The Big Pharma culture has been homogenized, purified, sterilized, whipped, stirred, filtered, etc and lost its ability to ferment the good stuff required to innovate. This isn’t covered in most reviews of the productivity challenge facing our industry, because its nearly impossible to quantify, but it’s well known and a huge issue.

These effects are variously attributed to a multitude of large cross functional committes, with all their associated bureacracy, making all the decisions very s-l-o-w-l-y......, risk aversion (i.e. ass covering) and unwillingness to kill bad projects before they've dragged on past their due date, and mega-mergers or internal reorgs that constantly stall projects while all the new players and pieces get assembled and reassembled. All of this plays havoc on continuity, quick decision making, empowerment of development teams, nimbleness, innovation, blah blah blah --basically all the positive characteristics organizations say they are striving for.

But the basic conclusion, for now, is that Big Pharma's culture is its own worst enemy when it comes to R&D productivity.  There seems to be a need to simplify and empower teams if you really want to see any results in an acceptable time frame.

The stakes are high too. If you doubt that, just look at this article from Fierce Biotech that details the R&D spending of the Top 10 Big Pharma -- which is topping $70 B per annum now.  Then look at the productivity of many of these same organizations as judged by new drug introductions in the last 10 years........not very pretty.

Posted by Bruce Lehr Apr 25th 2012.

 

Amgen warns biosimilar draft a threat to production innovation

The FDA is currently soliciting feedback to its recently published biosimilar guidelines.  Understandably, many among innovator pharma have comments to provide.  In its recent comments, Amgen asks the FDA if manufacturers are going to have to "maintain biosimilarity after approval."  If so, Amgen warns this requirement over time would stifle upgrades in manufacturing and quality improvements -- which would be bad for patients and a burden to the industry.  This could apply equally to innovators and biogenerics producers post-approval.

Amgen warns biosimilar draft a threat to production innovation.

Amgen suggests that a biosimilar applicant make its comparisons to the innovator product during a limited period of time and then establish a reference standard. Amgen then wants the FDA to treat the innovator product and the biosimilar as separae drugs from that point forward. Then each can make changes to their manufacturing or quality based on the mertis of their own data.

Industry commentators note however this would have implications on interchangeability -- likely the above approach would prevent these products from ever being considered interchangeable. Of course, Big Pharma and BIO have their reasons for not wanting to see interchangeability adopted anytime soon.

Posted by Bruce Lehr Apr 25th 2012.

 

 

 

 

Abbott Moves to Block Many Biosimilar Applications

The Biologics Price Competition and Innovation Act (BPCIA) was signed into law on March 23, 2010.  It is the basis for establishing an approval pathway for biosimilars.  In early April this year, Abbott petitioned the FDA to disallow any biosimilar applications that cited a reference drug's BLA that was submitted prior to the March 23rd date.  Abbott's legal representatives contend that the FDA's consideration of such materials would violate the Fifth Amendment. See Patent Docs blog.

It seems the Fifth Amendment, in addition to protecting one's right against self-incrimination, also "prohibits the taking of private property for public use without just compensation."  Abbott says the FDA would be dong just that if they use data from a BLA (filed before March 23, 2010) to allow a biosimilar drug on the market.  Prior to March 23rd, Abbott contends that it and other similar BLA filers had the expectation that the information in their filing would remain guarded as a trade secret, and the FDA is now about to reverse that policy.  Abbott specifically mentions BLA 125057 for Humira® (adalimumab) as one BLA to be protected in its FDA petition.  The drug is a known target of biosimilar "producers to be".  Even as I type, it is earning its way to becoming the TOP SELLING drug in the world in 2012 with more than $9.3 B in projected revenues.

Abbott's argument in a nutshell. 

Reference product sponsors invested massively in bringing products to market, taking great risk to develop, test, and seek a license to market the reference product.   Abbott argues that an innovator's  license application typically reflects more than a decade of research and contains analytical, preclinical, and clinical data, as well as detailed manufacturing information, most of which qualifies as trade secrets.  It further contends that these trade secrets are the private property of the reference product sponsor and are therefore protected by the Fifth Amendment to the U.S. Constitution.  And [the coup de grace] according to Abbott's Petition, when the FDA approves a biosimilar biological product on the grounds that the reference product has been shown safe, pure, and potent, it uses these trade secrets. Abbott says only biosimilar applications citing data filed after March 23, 2010 should be allowed.

Abbott finishes its Petition by requesting that the FDA interpret the BPCIA as applying only to post-enactment reference products, thereby avoiding both significant constitutional questions and significant governmental liability. 

 Abbott even cited a Supreme Court case -- Ruckelshaus v. Monsanto Co.  (1984) -- involving a somewhat analogous situation where Monsanto submitted a trade secret to the EPA in support of a pesticide license application.  The Supreme court did rule in this instance that trade secrets were protected under the 5th amendment and that Monsanto had an expectation that the goverment would not use the information to benefit a competitor in their license application -- instead their data "would remain inviolate."

Wow...this completely undermines the intent of the biosimilars legislation does it not?  Sounds eerily similar to me. I think it would be bad public policy to block biosimilars but I think Abbott's argument is ingenious to say the least.  Right now, this is just a petition to the FDA to influence how it chooses to set policy, now we'll have to wait anxiously to hear the agency response. You can see this argument potentially going to some court however.

Posted by Bruce Lehr Apr 24th 2012.