Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Biosimilars are very much a hot topic of late.  They are approved new versions of innovator biopharmaceutical products, following patent expiry.  Essentially, this is like a generic version of the biologic product, hence their alternative name, follow-on biologics.

Recently, the FDA approved the Momenta/Sandoz’s follow-on versions of sanofi-aventis’s Lovenox, a low molecular weight heparin (LMWH), used to prevent and treat deep vein thrombosis or pulmonary embolism.   The patent expired in July 2010 and approval was given on July 23rd.  Reports in the press suggest that erosion of the brand was both fast and steep, with a 60% shift in market share to the cheaper versions almost overnight.

At present, the FDA doesn’t have a recognised approval system for follow-on biologics, so the process is somewhat fuzzy.  I’m not sure why the FDA approved Momenta’s versionof enoxaparin, but not Teva or Amphastar’s, although inevitably, there was a lot of noise surrounding the issue in the press over the last year.  I’m not going to go into the details of the shenanigans over this, but a quick Google search will offer more information than many will have time to read!

What was interesting to me was that Momenta scientists published an interesting paper in Nature Biotechnology (reference below) on Chinese hamster ovary (CHO) cells.   CHO cells are the most common cells used to synthesise recombinant proteins used in many drugs and are extremely well studied.  Previously, however, CHO cells were thought to lack the biosynthetic ability necessary to synthesize a particular glycoprotein, but the Momenta scientists found otherwise, underlining their expertise and research in this field.

These players – Momenta, Sandoz, Teva and Amphastar – probably have the lead in follow-on biologics for now, so they will be interesting companies to watch out for as the patent cliffs in biologics begins to hit big Pharma between now and 2015.

Now, while the FDA still doesn’t have any official regulations for follow-on biologics, the European Medicines Agency (EMA) has begun to tackle the issue head on, posting draft guidelines last week.  You can check them out online.  According to the EMA:

“The Agency has released the draft guideline on similar biological medicinal products containing monoclonal antibodies for a six-month consultation period.

The guideline lays down the requirements for medicines containing monoclonal antibodies that claim to be similar to another such medicine already marketed.

Comments on the draft guideline can be submitted to the Agency up to 31 May 2011.”

Unfortunately, I haven’t had time to digest the EMA proposals yet, but we will post a full synopsis in a future blog post soon.

If you have any thoughts, comments or questions, please feel to add them in the comments below.

References: Bosques, C., Collins, B., Meador, J., Sarvaiya, H., Murphy, J., DelloRusso, G., Bulik, D., Hsu, I., Washburn, N., Sipsey, S., Myette, J., Raman, R., Shriver, Z., Sasisekharan, R., & Venkataraman, G. (2010). Chinese hamster ovary cells can produce galactose-α-1,3-galactose antigens on proteins Nature Biotechnology, 28 (11), 1153-1156 DOI: 10.1038/nbt1110-1153

11 Responses to “What's new in Biosimilars?”

  1. Docnuman

    Hi Sally,

    Love your blog.Just wanted to make a quick comment about Teva.To the best of my knowledge Its enoxaparin is not yet approved.The only approved generic in the U.S. is from Momenta/Sandoz.


    • maverickny

      Hi Doc, good to see you again. I’ve been having a series of ‘blonde moments’ since yesterday after my car wouldn’t start and only realised today that it had been left in Reverse. Oops.

      You are totally correct and the post has been updated; I knew this, but completely forgot.

      PS How was the AACR Molecular Targets meeting in Berlin – any memorable highlights for you?

      • Docnuman

        Hi Sally,

        The AACR meeting was awesome.The concept of synthetic lethality involving parpi and Chk inhibitors generated a lot of buzz. Looks like immunotherapy might stage a comeback thanks to Ipilimumab. Will be at ASH.If possible hope to connect with you there.

        Take care

        • maverickny

          Hi Syed,

          Yes I will be at ASH, would love to catch up with you then.

          PARPi and Chk inhibitors both look very promising indeed.

  2. Haberman Associates

    At least as of late 2008, the FDA did not consider complex mixtures of carbohydrates, such as Sandoz/Momenta’s M-Enoxaparin, to be biosimilars, but ordinary generic drugs, which can be approved under the U.S. Food, Drug, and Cosmetic Act of 1938 (FDCA). Given the language that the FDA used in the approval noticed that you linked to, that still appears to be true.

    It is the approval of protein drugs–true biosimilars or follow-on biologics–that present regulatory difficulties in approval in the United States.

    Allan B. Haberman, Ph.D.

    • maverickny

      Agreed Alan, but that probably speaks more to the FDA viewing Lovenox as a very complex sugar molecule rather than a true biologic itself, so what we have is essentially a generic approved through the normal NDA channels.

      I agree that the true biosimilars will have more challenges in the face of no guidelines. The point of the blog was more about the EMA guideline process – at least they are starting down the road of developing appropriate processes.


    Thanks for the interesting blog. Momenta succeeded in getting approval for SNY’s Lovenox and is now going after Teva’s #1 seller Copaxone. Teva and Amphastar are angry that they filed 2 years before MNTA filed yet still have not been approved. They might have a case if we were talking about a simple drug like Lipitor which can be easily copied. But Lovenox is a very complex drug with many sugar chains and very difficult to copy. The FDA approved only the generic from the late starting MNTA which had used its superior patented MIT based algorithyms and technology to more fully characterize Lovenox than the other 2 generics. Amphastar was so ticked off it hired a detective to dig up some dirt on the FDA’s Dr Woodcock. Amphastar thought Dr. Woodcock was wrong to appoint MIT professor Ram Sasisekharan to lead an FDA task force that in 2008 investigated tainted Chinese-made heparin. The reason why the FDA chose MNTA was because they needed their expertise. MNTA has several other heparin related drugs in their pipeline and this area is their field of expertise. The FDA had to act fast because the heparin contamination had led to almost a 100 deaths. Imo the FDA got a bum rap for asking MNTA to help end this deadly heparin crisis.

    Mike Guiltinan

    • maverickny

      Ah yes, the heparin fiasco was an interesting but very sad event, Mike. I agree that Momenta have expertise in this field, as witnessed by their published research, but it was unfortunate that the other event created a sense of impropriety even if none was actually there. The PR disaster that followed did no one any favours.

  4. MarianCutler

    It’s telling that the EMEA posted draft guidelines specific to biologics containing monoclonal antibodies. Fact that they have to slice the marketplace up along such specific corridors speaks volumes to the complexity, lobbying and intricate decision making necessary to navigate the biosimilars landscape.

    Found it reassuring that the EMEA recommends human clinical trials to show both efficacy and safety of these products. Different than the debate happening around the FDA and Congress about the fate of biosimilars where there’s a serious stronghold pushing for bioequivalence measures only without human trials. From a personal and scientific perspective, I can’t get behind bioequivalence alone as a marker for compatability when it comes to biologics.

    Ask anyone connected with the science of these products and the space between similar and identical is simply too great of a leap leaving many to ponder what safety risks are left for the patient and doctor to traverse. As we all know, biologics are nothing like their distant cousins — chemical drugs. With safety being the biggest gap for adoption.

    Consider that we do have a small handful of examples to point to which indicate the market has issues with biosimilars … possibly issues even clinical trials may not be able to overcome. For example, the EMEA has approved biologics with the competitors to Epogen. I believe three biosimilars were approved to compete with Epogen and none of them have been readily embraced by the medical community and their uptake is fairly grim from a marketing perspective. The same holds true in the US, where we have a biosimilar approved by the FDA in Omnitrope (treats growth failure in children) in 2006 and it was just listed by NICE as the “first recommended biosimilar” (June 2010). Interestingly, the trajectory for these biosimilars seems to be closer to lesser versions of “me too” products with doctors slow to switch patients and more comfortable prescribing the innovator product.

    Obviously, biosimilars are coming and the EMEA is head and shoulder above the US in creating regulatory approval pathways that are rationale, reasonable and put patient safety front and center. What is needed is more widespread adoption and use is a concerted effort to convince and convert physicians, advocacy and patients that these biosimilars are tried and tested versions of the innovator products.

    But, most of all, we need to know that the 20% savings (which might be a best-case discount considering the development and manufacturing costs associated with biosimilars) does not come at the expense of some unforeseen side effect which could make the treatment worse–possibly infinitely worse–than the disease being treated.

    Efforts to shift perceptions are sadly lacking and deeply needed. But, in this case, show me the data is about the only way to a break out biosimilar.


  5. Haberman Associates

    Although there is a major focus on biosimilars/follow-on biologics, some of us (myself included) are more enthusiastic about second-generation biologics, also known as “biobetters”.

    For example, Merck’s entry into the biosimilars arena is largely facilitated by its 2006 acquisition of GlycoFi (Lebanon, NH). This glycobiology specialty company has developed engineered yeast strains that can be made to express glycoproteins bearing human glycans.

    Such strains can be designed to produce biosimilar versions of branded biologics, which are typically mixtures of glycoforms (species of glycoproteins with the same polypeptide backbones but different carbohydrate compositions). However, they can also be designed to produce single-glycoform biologics, with optimal therapeutic properties (e.g., better efficacy and potency than the original biologic product, allowing for a lower dose, and with the potential for improved safety).

    These products would constitute second-generation biologics, and must go through human clinical trials and the FDA approval process for a new drug. However, they would enjoy a lengthy period of exclusivity and might be able to command a premium price. Since they would go through clinical trials, they would not carry the same concerns about safety that poorly-tested biosimilars might, as pointed out in the earlier comment.

    Merck however, seems to be aiming initially at developing biosimilars, and might develop second-generation, single-glycoform biologics later. There are also other technologies for developing second-generation biologics, which are being implemented in other companies.

  6. hecatom

    Didn’t heard of biosimilars and Chinese hamster ovary (CHO) cells. In fact never have been interested in hamster ovary. I will do my research.

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