The Big Red Biotech Blog

Abbott Challenges Biosimilar Legality

This from today's Xconomy.  Abbott has filed a citizen's petition with the FDA to protect Humira by challenging the notion that the agency can refer to Abbott's Humira BLA filing.  Their argument (posted here and here before) is that this would violate the "takings clause" in the 5th amendment that prohibits the taking of "private property for public use without just compensation."

Abbott has argued that its BLA contains trade secrets that would be "taken" without compensation should the FDA use the BLA contents to potentially license a new biosimilar.  Since Abbott's Humira sells in neighborhood of $9 B per annum worldwide, "just compensation" would be considerable in this instance.

So we can expect pharma industry participants to line up on both sides of the question with their teams of lawywers?  On one side, the innovators who have no plan to introduce biosimilars will join Abbott. On the other, we should expect innovators who do have plans to introduce biosimilars and companies who plan to focus only on biosimilars.  There is bound to be plenty of action.

We should also have the government and healthcare advocates lining up to argue for biosimilars on its economic merits to reduce costs in the health care system and for patients.  And on the other side, free market forces will argue for the innovators right to protect their IP and earn a return on its investment for their shareholders. Both won't be right or simultaneously get their way.  Let the games begin.

Posted by Bruce Lehr Jun 25th 2012.

 

India launches 'similar biologics' guidelines

The Indian Government launched its biosimilars guidelines at this year's BIO meetings. The guidelines are aimed at providing a "clear" regulatory pathway for manufacturers of biologic similars and will be applied to new filings now.

India launches 'similar biologics' guidelines at BIO2012.

Manufacturers must prove similarity to a reference product -- either an innovator drug in licensed in India or approved elsewhere.  There is also a requirment for 4 years post-market surveillance on safety data.

The motive for India to promote these guidelines is to encourage more domestic and foreign investment in biosimilars in India with an idea to increase product access and to reduce4 goverment spending on drugs.

Dept of Biotechnology secretary, Maharaj Bhan,  said,  "India needs drugs at reasonable prices so we have to worry about the issue of access so we have to spur innovation and manufacturing in India.  We also need to create an environment where International companies will be interested in using India as a place to manufacture drugs."   The latter comment relates directly to the previous blog post on India's need to raise GMP compliance.

Posted by Bruce Lehr Jun 25th 2012.

China Changes Patent Laws To Get Cheap Drugs

Oh-oh! China's new IP law allowing compulsory licensing of drugs under patent came into effect as of May 1, 2012. The revised law is called the Measures for the Compulsory Licensing for Patent Implementation and is expected to open the doors for low-cost generic versions of patented drugs. The law also allows export of these drugs to other countries.

China Changes Patent Laws To Get Cheap Drugs // Pharmalot.

China announced this move in a seminar last month.  It seems to confirm that China's intent is to become a generic producer for the domestic and international market. Now we have both China and India issuing compulsory licenses.

Global drugmakers need to take heed as China already has many companies producing active ingredients for domestic and global suppliers. They can make generics and apparently will. With both India and China moving toward making more generic copies of patented drugs, this can't do anything but put more pressure on Big Pharma revenues. It looks like the pharmerging markets won't necessarily offer virgin territory to be mined by Western companies looking to gain compensory sales to make up for lagging sales in the West.

Posted by Bruce Lehr June 8th 2012

 

Indian minister rails against anti-generics smear campaign

The Indian government says multinational companies are running "a concerted campaign" against its generics industry!

Indian minister rails against anti-generics smear campaign.

"A concerted campaign against Indian pharma industry has been launched by MNC's whose interests are getting adversely impacted due to increasing global presence of Indian pharma companies", said Shri Anand Sharma, Indian Minister of of Industry and Commerce.

India is now billing itself as the "Pharmacy for the World" in response.  A central theme in this campaign is to show generic drugs produced in India meet the quality standards of drugs produced in Western countries or by Western competitors.

India is not going to take it anymore.

 

 Posted by Bruce Lehr May 9th 2012.

Biosimilars Not Only Threat Facing Biopharma

As this piece from BioProcess Blog points out, biosimilar competition is only one hazard faced by biopharma producers of the world's top bio drugs. In addition to increased price competition, there are the unscrupulous drug counterfeiters (see recent Avastin issues).  There is also the possibility of compulsory licenses being invoked in places like India (see recent Nexavar case). 

Biosimilar Competition is Only One of Several Threats Facing Biopharma Blockbuster Drugs.

These type of developments led PhRMA President and CEO John Castellani recently to comment, "If countries begin to routinely use complusory licenses, we could see a 'race to the bottom' in which governments in the developing world walk awayfrom their responsibility to support research and innovation in public health. In the absence of investment made by our members, and the resulting research and development, there would be no generic medicines for the world's patients."

As we say in Oz, "Biosimilars, Counterfeits and Compulsory Licenses, Oh My!"

 

Posted by Bruce Lehr May 8th 2012.

First mAb Submitted to EMA for Biosimilar Approval

A biosimilar version of Remicade (anti-TNF drug) is the first mAb to be submitted to the EMA for review.  Celltrion is believed to be the company making the submission, although this has not been formally revealed.  Celltrion has conducted clinical trials with its version of the drug in 19 countries over the past 2 years. There are 16 -- yes 16 -- approved indications for Remicade.  It is not known if Celltrion is seeking approval for only the RA indication (matching trials) or going for additional indications as well.  Extrapolation of safety and efficacy data from one indication to others is allowed potentially so it is a pertinent question.

First Monoclonal Antibody Submitted to EMA for Biosimilar Approval.

 The anti-TNF market is estimated to be worth $21 B. Analysts are torn as to whether a biosimilar version is a bigger threat to J&J's Remicade or whether a (humanized) biobetter version of the antibody will more likely prevail.  J&J has its own humanized replacment called Simponi. Celltrion is betting on gettig share however and is submitting its application well ahead of Remicade's 2014 patent expiration date. Celltrion will also go to Korea and other emerging markets in Asia and Central/South America where Remicade is not under patent.

Now, we all wait to see how Celltrion's application does at EMA.  More mAb biosimilar applications are expected to be submitted to EMA this year.  Whether these have a huge impact on the market, depends upon how easily they are approved and whether companies like Celltrion (or Samsung) can make good on their promise to drop prices by 40-50% over the reference product. The race has begun in earnest now.

Posted by Bruce Lehr May 2nd 2012.

More on Abbott Anti-Biosimilar Petition to FDA

I posted a few days ago on Abbott's letter to the FDA urging it to reconsider its policy on reviewing biosimilars.  Abbott argues that to approve any biosimilar that is challenging a reference product filed prior to the law's enactment in March 2010 will necessarily cause the FDA to use innovator company trade secrets in their analysis -- and thereby violate provisions in the 5th amendment.  Provocative, yes?

If Abbott's argument is correct or at least has good chance of being found so in the federal courts, this would seem to completely undermine the intent in geting biosimilars approved, and certainly would hamer any positive healthcare budgetary effects (i.e. saving drug costs) that Congress may have been seeking in passing this legislation.

Read more here in today's Pharmalot blog.

Posted by Bruce Lehr May 1st 2012.

PhRMA Criticizes Biosimilar Flexibility

PhRMA has weighed in with its comments to the FDA guidelines on biosimilars.  In those, the trade group says that the FDA should not allow biosimilar manufacturers potential flexibility in delivery devices and formulations -- and still regulate it as a biosimilar.

PhRMA speaks out against FDA biosimilar flexibility.

A spokesman for PhRMA said, "Intentionally introducing differences to the molecule or the finished product will increase the level of uncertainty regarding the proposed biosimilar's similarity to the reference product. The statute imposes a scientifically rigorous standard that each product must be highly similar to its reference product.  Statutory considerations therefore cousel that FDA guidance should recommend that applicants minimize controllable process and design differences."

Several Big Pharma and BIO have weighed in with similar comments. 

Posted by Bruce Lehr Apr 30th 2012

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

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.

 

 

Biosimilars: If You Can't Beat 'Em Block 'Em

The Alliance for Safe Biologic Medicines urges the FDA to adopt "steps to ensure patient safety is at the forefront of the biosimilars pathway."  Further, the FDA needs to "make clear that clinical studies will be necessary for the foreseeable future due to the complexity and diversity of human biology and the limits of scientific knowledge today."  The Alliance is a trade organization composed of biopharma companies and individuals that has set up to advise the FDA on biosimilars policy while it is under discussion (i.e. a trade lobby).  Company's like Novo Nordisk and Roche (Genentech) are members.  See in-Pharma Technologist and Fierce Biotech here and here.

They appear to be asking the FDA to make its proposed regulations less flexible than they are currently written and to impose more strict guidelines requiring clinical trials, as well as sterner traceability measures and a pharmacovigilance system that "distinguishes a biologic reference product from its biosimilar."

I've written before that I think delay tactics to make it harder to get biosimilars to the market (and at a higher cost) are so much whistling past the graveyard (see blog post).  To me, the economic and government forces favoring the implementation of biosimilar guidelines and subsequent approval of these products is a given.  Governments want to save on healthcare costs, it's that simple.  Will they compromise safety to do so?  No.  But, I think they will try to set up flexible approval systems that give the regulatory bodies some latitude to approve some biosimilar applications faster than others with more or less clinical data support needed depending on the situation. The FDA seems to be giving itself some flexibility.

I don't see innovators trying to delay implementation and market competition as a very effective strategy.  It's ironic that many of the innovators themselves are likely to be among the first biosimilar applicants (with a competitor's drug of course).  I'm further amused that many of these same companies are simultaneously in favor of other legislative efforts underway (FAST, TREAT, etc.) to speed the drug approval process.  In that instance, they've suggested only safety data is needed and a "case by case" consideration of drug licenses -- particularly for diseases without other good treatment options -- is just the way to go (see blog posts here and here).

I think we should get on with it.  Get biosimilar guidelines in place and get the process toward approval started. Biosimilars ARE coming.  If innovators want to be innovators, then innovate. If they want to be biosimilar competitors, then compete -- but don't block or slow the process down.

Posted by Bruce Lehr Apr 18th 2012.

 

Lilly Can't Save Its Way to Prosperity Says CEO

Lilly's John Lechleiter says the company can't solve its upcoming revenue woes, due to expiring patents on some of its biggest sellers, by cutting staff and otherwise saving costs. He says that Lilly has no plans to follow companies like Pfizer in cutting $1B from operations in 2012.

Eli Lilly CEO Says Cost Cutting Won’t Solve Drug Sales Loss - Bloomberg .

Lechleiter continues to state his mantra that Lilly has to develop its way of its problem by bringing winners from its pipeline to market.  The next candidate is solanezumab -- a putative Alzheimer's treatment in phase III -- one that some analysts indicate could be worth as much as $9 B in peak sales.  But, he is also quick to point out that solanezumab is high risk and it is NOT a make or break proposition for Lilly.  Nevertheless, the pressure is on to bring home some winners soon from Lilly's pipeline.

AZ's chief, David Brennan, on the other hand is following a plan of reduced spending on internal R&D and is hoping to boost that company's flagging pipeline in the near term by acquiring smaller bolt on acquisitions (can anybody say "string of pearls"). They've also struck a recent deal with Amgen to help take some of the latter's Mab drugs through the pipeline.  However, AZ still needs more to right its ship -- given its patent cliff and dreadful recent record in developing drugs in its own R&D groups. Can they find enough "bolt-ons" to buy their way out of trouble appears to be the salient question?  See Fierce Biotech.

Will either strategy work?  Both appear to be tenuous at best.

Posted by Bruce Lehr Apr 13 2012.  

 

New Lipitor Leader in the Clubhouse -- Ranbaxy

Since it is Master's season, I thought I'd go with the golf analogy.  The WSJ Health blog reports that as of last month Ranbaxy's generic version of Lipitor is already outselling Pfizer's original drug. It just goes to show the incredible pace at which generics are now able to overtake the innovator product once it comes off patent.  Presumably this is due to the tremendous cost savings one can get with a generic. 

Incredibly (to me) Ranbaxy only began selling its generic Lipitor (atorvastin) Nov 30th last year and as of the last week in March it sold 17.5 M pills for that week compared to Pfizer's 17.2 M -- at least that is the report according to Wolters Kluer Pharma Solutions.  All I can say is WOW!

Ranbaxy may not have the fabled jacket but they do have the GREEN. 

Posted by Bruce Lehr Apr 6th 2012.

Biosimilars— Big Pharma Whistling Past Graveyards?

This from the PharmTech blog.  I want to focus on cooments by the first speaker in the post, Neil Mahoney, President & CEO of Global Pharma Alliance. His talk indicated that it would be much more difficult to produce a biosimilar than for a generic small molecule - which is clearly true -- but he also cited a cost of $100-$200 M to develop a follow on biologic.  Wow!

PharmTech Talk » Biosimilars—It’s the Differences That Really Matter.

I think that figure has to be looked at with skepticism and if true would only apply to a US market.  But we have a GLOBAL pharma industry now.  Estimates from Dr. Reddy's lab indicate that a western company could expect to spend $50-$100 M to develop a biosimilar (half the figure cited above) -- but also than an Indian company could expect to do this for only $10-$20 M.  Additionally, India can be expected to offer the products at 25-40% less.

Dr. Mahoney also trots out data that says the initial biosimilars lanched in Europe did not exactly take the market by storn in terms of share -- also true. But to suggest that this trend will hold up going forward is folly I think.  The first round of biosimilars were drugs like EPO which were not nearly as costly to use as the next round of mAbs to treat things like RA or cancer.  Given the current health crisis, and government austerity programs, I cannot doubt that there will be incentives in place to encourage development and approval of biosimilars throughout the world -- yes -- even in the US.  Moreover, as more of the mainline pharma companies like Pfizer, Merck, Novartis (Sandoz) etc start pushing biosimilars, I expect the adoption rates to increase and the price erosion to accelerate. 

While biosimilars will require more investment and skill than small molecule generics, I don't think that is insurmountable.  Economics and healthcare policy will drive their existence.  It is only a matter of time in miy mind and that time will be quicker than a lot of naysayers believe.  I think any thought to the contrary is wishful thinking and amounts to "whistling past the graveyard".

 

Posted by Bruce Lehr Mar 16th 2012.

Of the FDA, Biosimilars and Elephants

The Patent Doc blog covered a recent FDA presentation (Dr. Rachel Sherman, Feb 15th) on the biosimilar guidance documents issued earlier this month.

This FDA used entertaining analogy to demonstrate the thinking process in this determination.  The presentation contains a line drawing of an elephant (below), where each line represents an analytical or clinical study performed by the biosimilar applicant.  The FDA will have to compare the reference product (figure A) with the biosimilar products (figures B-E) to determine what level of detail is required for a determination of biosimilarity (whether the drawing is an elephant or not).  The biosimilar applicant will attempt to draw the minimum amount of lines such that the FDA can make a finding that the biological product is biosimilar to the reference product (elephant).  The FDA will not permit any "tracing" of the lines in the drawing, as these attributes of the biosimilar are already known.  Each test or study must add something to the whole body of evidence.  This elephant analogy is also used to define "fingerprint" studies, which may tell the biosimilar applicant at an early stage that its product will not qualify for approval under 351(k) (e.g., if early lines in the drawing show a beak or fins).

This got me to thinking about the old Jain proverb of the Six Blind Men and the Elephant.

The story says that six blind men were asked to determine what an elephant looked like by feeling different parts of the elephant's body. The blind man who feels a leg says the elephant is like a pillar; the one who feels the tail says the elephant is like a rope; the one who feels the trunk says the elephant is like a tree branch; the one who feels the ear says the elephant is like a hand fan; the one who feels the belly says the elephant is like a wall; and the one who feels the tusk says the elephant is like a solid pipe.

A king [FDA] explains to them:

"All of you are right. The reason every one of you is telling it differently is because each one of you touched the different part of the elephant. So, actually the elephant has all the features you mentioned."

This resolves the conflict, and is used to illustrate the principle of living in harmony with different beliefs and that truth can be stated in different ways.

 

Here's hoping the FDA can harmonize its biosimilar elephants by using a process "where each analytical study required of biosimilar applicants will advance the field of knowledge regarding the molecule of interest."

Posted by Bruce Lehr Feb 28th 2012.

Shhh! My Bioproduction Processes are Secret

Mass High Tech today picked up on a theme that is being increasingly bandied about now that biosimilars are becoming a reality in the US -- that being companies may eschew patents in favor of keeping intellectual property information as 'trade secrets'.

The concept is that biosimlars rely much more on production processes as a critical feature to produce the reference molecule -- which a biosimilar maker would like to be able to match or certainly know about in detail.   Patents on processes typically can require disclosure of detailed information that would make "copying" the process or more to the point designing around its patent claims more easily accomplished.  

Trade secrets on the other hand -- are well -- secret.  There is no public disclosure and if you keep your mouth shut (your company's collective mouth shut), you can keep the secret for an eternity in theory.  Patents of course have a finite lifespan of 20 years.

The upshot is that many innovator (or biobetter) companies may now be concluding that to protect themsleves from the expected biosimilar onslaught, they should simply stay quiet on their processes. The "don't ask don't tell" version of the biosimilar world.

Posted by Bruce Lehr Feb 16th 2012.

Biosimilars are Progressing by the 'Totality of Evidence'

Two more blogs weigh in on the FDA guidelines published for the Biosimilar approval route last Thursday.  The Patent Doc blog seems a bit underwhelmed by the lack of specificity of the guidelines but acknowledges the FDA had a relatively short time line to issue their guidance.  It does acknowledge the guidelines will likely evolve in practice and the FDA gave itself maximum flexibility in interpreting them. The FDA will use a "totality of evidence" standard similar to that adopted in Europe.

The BioProcess Blog for its part seems a little more upbeat that the FDA put guidelines out there to get the process rolling.  In general, it was positive about the fact the FDA will allow the possibility of formula changes and different delivery devices from biosimilar to the reference product without either being an automatic block to taking a biosimilar path. The blog authors were also happy that the FDA will accept data from non-US licensed products in considering the "totality of evidence" in support of a biosimilar application.

To date the FDA has received 31 requests for meetings to discuss company plans for their biosimilars, and 21 of those had been held by the end of December 2011.  There have also been 9 INDs for biosimilars filed to date and the agency is expecting a full 351(k) application soon.  The process is well underway and there is still 60 days for interested parties to comment and suggest changes to the Draft guidelines just issued.

Posted by Bruce Lehr Feb 15th 2012.

Biosimilar Guidance Is A Pandora’s Box: Pan Explains

This is a really interesting short interview from Pharmalot with Jonathan Pan, a manager at the Scientia Advisors consulting firm on his view of what the FDA draft guidelines on biosimilars could mean.

Biosimilar Guidance Is A Pandora’s Box: Pan Explains // Pharmalot.

I excerpted a part I found very interesting concering how the FDA is [apparently] setting up to judge biosimilarity. And how this might open up opportuntities for pharma to get drugs to market as "biosimilars" instead of new entities.

Pharmalot: So was there anything surprising here?
Pan: The major surprise I see here is that FDA is creating a path of similarity versus a path of replication. Effectively, what they’re doing, because of the complex nature of these products, is they’re saying that, for any biologic agent, anybody can create a biosimilar, but that it may not be an identical product. At the end of the day, it’s creating a great way of making a ton of non-inferior products to a particular reference product.

Pharmalot: Aren’t they going go to go on a case-by-case, though?
Pan: Obviously, they leave that language open and, of course, no guidance from FDA is set in stone, but at the end of the day, it’s interesting how they worded this to mitigate the fact that compounds are very complex and because of that, there’s more opportunity for companies to move their products to market. I think if a drugmaker wanted to pursue a biosimilar path versus the new molecular entity, they make take the biosimilar path, because it’s a quicker route to market.

Look, take the rheumatoid arthritis market. If we have one anti-TNF inhibitor, all I have to do is show it’s equivalent to how one of them works… I just have to make a decision to make a biosimilar and go to FDA and say I’ll run a trial to show that it’s safe and my antibody is going to be non-inferior. The FDA, according to the guidance, would say the product is non-inferior and, therefore, it will be approved as a biosimilar.

That’s versus going through a Phase I trial and recruiting patients, and a Phase II trial and recruiting patients, and a Phase III showing superiority for standard of care… They won’t have to go through the regimented process. It’ll be more abridged. As long as they can show in standard pharmacokinetic and pharmacodynamics tests that the product is non-inferior to the reference products. They’ll be going head to head. They’ll still have to go through safety checks and efficacy checks through clinical development plan, but what most pharmaceutical companies do is cherry pick… in this process, they’ll simply try to compare to reference products.

Pharmalot: What, if anything do you see as potentially troubling?
Pan: There is a Pandora’s box here. If implemented in its current state, I imagine there will be some interesting maneuvering. If I’m a pharmaceutical company and any product is at Phase I, I may not want to go through the full development process and instead say that I have a biosimilar and get to market as fast as possible. It’s a new thought process pharma may or may not want to embrace. It’s good for the pharmaceutical industry as a whole because it allows them to get products on the market that may not get on there otherwise.

OK do we have a new way to get similar biologic products to a licensed drug to market?  Or do we have a way to get a new entity to market faster by calling it biosimilar?  Or do we have both?

Posted by Bruce Lehr Feb 10th 2012.

FDA Unveils Guidance for Biosimilar Development Today

The FDA posted its draft guidance document for biosimilars on its website today.  You can read a summary below outlined in the PharmTech Talk blog.

PharmTech Talk » It’s Here: FDA Unveils Guidance for Biosimilar Development.

Or you can go see the full document yourself on the Agency's site.

The FDA site notes that comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the availability of the draft guidance. Many comments are expected. Everyone - Have at It.

 

 

Posted by Bruce Lehr Feb 9th 2012.

 

 

FDA Gives Biosimilars Update

Rachel Sherman, Associate Director for Medical Policy, within CDER gave an update on biosimilars today. Protein biosimilars (but not chemically synthesized polypeptides) will be regulated under Public Health Services Act section 351. 

PharmTech Talk » FDA Gives Biosimilars Update.

The 351 (k) approval route will require the FDA to consider:

• Analytical studies to show th ebiosimilar is highly similar to the reference product
• animal studies (including toxicology) as needed
• clinical studies to establish safety, purity and potency in one or more conditions of use for the reference product

To assess biosimilarity, Sherman explained that each study adds a piece of information to understand what a biosimilar product is and is not, and what other information is needed. The FDA may also adopt the European approach to "use the totality of the evidence" to address biosimilarity.

To date, there have been 35 Pre-IND meeting requests for proposed biosimilars to 11 reference products, 21 Pre-IND meetings held and 9 INDs received at FDA. The line is rapidly forming.

FDA guidance has not appeared as yet, and is still in "final stages" at the agency.  No timeline for publication has been issued.

Posted by Bruce Lehr Feb 3rd 2012.

 

More on Relative Value of Patents for Bio Drugs in a Biosimilar World

More from the Patent Doc blog on why biologic drug producers in the future will stay away from patents and rely more on trade secrets to protect their interests. The Biologics Price Competition and Innovation Act of 2009 (particularly the litigation provisions) contains incentives for biologic drug innovators not to rely on patents to protect these drugs and the return on investment.  A recent analysis also showed that patent protection provides (on average) about one additional year (~327 days) of exclusivity past the end of the 12-year exclusivity provided by the BPCIA. So statutory protection is about equivalent with patent protection and the former can be accomplished through much less information disclosure on one's biological drug.

The blog post below talks about using trade secret approach more in late stages of development for process related steps like cell line optmization -- that generally doesn't benefit from patent protection.  This would make it harder on a follower to try to copy a bio-drug.

...the expected de-emphasis on patent protection for later-stage development (including regulatory approval) can be expected to change the relative importance of patents in the two stages.  Such de-emphasis will also change where the valuation in biologic drugs may lie, because there will be a relatively greater advantage in optimizing cell lines and other process parameters (which even today rarely benefit from patenting) than in patents on the biologic drugs per se. 

So less emphasis on composition of matter and more emphasis on the process. The author further concludes that "the future will be different than the past regarding biologic drug development and efforts to obtain the benefits of biologic drug development at a reduced price."

Posted by Bruce Lehr Dec 26th 2011.

Bio-drug Innovators Eschew Patents in Future to Block Biosimilars?

Here's interesting post from the Patent Doc Blog that argues that there are incentives for producers of innovator drugs to NOT file patents to block information access to biosimilars producers in the future.

The writer argues that instead of filing patents innovator drug producers could file the bare minimum information with the FDA to get their drug approved.  Because biologic drugs are so complex, this degree of stealth would prevent knowledge flow to biosimilar producers who wanted to copy their drug. Thus, the innovator would not disclose the cell used to produce the drug, or any optimization of that cell line.

The bloggist argues that this would produce obstacles for the biosimilar follower and would also avoid litigation under the biosimilars statute. The innovator could thus avoid protracted biosimilar patent infringement lawsuits. 

It is an interesting post.  But if non-filing is this easy, why doesn't someone do it now? It would save time and money.  It may protect from a biosimilar follower but does it protect from a fellow innovator?

Posted by Bruce Lehr Dec 20th 2011.

Analysts Pick at Logic of Amgen and Watson Biosimilars Deal

Here's some follow up on the announced Amgen and Watson biosimilars deal yesterday where the analysts weigh in on their impressions of the deal.

Amgen, Watson & Biosimilars: What The Wags Say // Pharmalot.

Said Bernstein Research analyst Ronny Gal, “we tend to think there is not enough money in biosimilars to justify the host of branded companies marching into the field (Pfizer, Merck, Lilly, Biogen and now Amgen), especially as their entry provides a self-fulfilling prophecy for product commoditization.”

Moreover, Amgen may find itself in a tortured position trying to explain to physicians why they should choose certain brand-name meds over future biosimilar rivals, while at the same time taking the opposite tack to co-promote any biosimilar that is developed and marketed as part of the collaboration with Watson. He uses an example of a Roche and Genentech drug, since these are the key targets for the deal, to illustrate his point.

“This feels a lot like branded company participation in generics in the ’80’s, which ended with mass exit from the field. It will require some serious mental gymnastics to explain to an oncologist why Avastin can be replicated while Aranesp cannot. Further, the argument will be used against Amgen well before its biosimilar products come to market.”

Valid points to raise with regard to the marketng challenges in this deal.  One also neds to remember that some of the traditional powers in generics, e.g. Teva, Sandoz, Hospira, will also be trying to sell into this space.  That's pretty heady competition in a market segment with acknowledged lower profit margins.  It's hard to see that some big competitors won't be chased from the field of battle.

Posted by Bruce Lehr Dec 20th 2011.