Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Trastuzumab Pertuzumab’

At the 2013 Annual Meeting of the American Society of Clinical Oncology in Chicago this past weekend, my impression of one of the most popular posters in terms of how fast the poster handouts disappeared (all 100 went in 7 minutes) was a phase 1 trial comparing PF-05280014, a potential biosimilar to trastuzumab (Herceptin) in healthy volunteers (ASCO 2013 Abstract No: 612)

Herceptin is used for the treatment of HER2+ breast cancer, and with global sales of over $5 billion, represents a major source of sales to Roche. However, Roche’s patent for Herceptin is expected to expire in 2014 in the UK, 2015 in Europe and 2019 in the United States, providing an opportunity for other companies to take a significant share of this market away from them.

Roche have long focused on life cycle management with strong patent defense built in to their long term strategic plans. In this case, their approach has been to launch new breast cancer products in the HER2 segment such as pertuzumab (Perjeta), for use in combination with Herceptin, and Kadycla (T-DM1) for advanced breast cancer patients who become treatment resistant to Herceptin. Trials are ongoing in the front-line setting with the goal of replacing Herceptin.

Several companies, including Amgen and Novartis, are looking to develop a biosimilar to Herceptin for the treatment of HER2+ breast cancer, and it now looks like Pfizer is in the race too. A biosimilar product is not a generic “copycat” i.e. a copy of a small molecule chemically synthesized to provide equivalent efficacy. Instead, a biosimilar is a copy of a biological compound such as an antibody or protein produced by living organisms intended to be equivalent to the original product. In general, monoclonal antibodies are much more difficult and complex to re-engineer than a pill or TKI.  This means that the main competitors in the biosimilar market are more likely to be generic offshoots of big Pharma rather than Indian generic companies, since they possess the technology and resources to engineer monoclonal antibodies.

There’s a lot of debate over biosimilars and whether they are truly identical. In the United States, the Biologics Price Competition and Innovation Act (BPCI) contained within the Affordable Care Act provided a regulatory route for biosimilars to be approved by the FDA, so long as they could be clinically shown to be “highly similar.”  Once approved, biosimilars are expected to be interchangeable, i.e. substituted for the original product with the expectation that lower drug prices will be the result. This represents a major competitive threat to Roche’s Herceptin HER2 franchise.

Interestingly at ASCO, Pfizer did not provide a QR code that linked to a PDF copy of their PF-05280014 poster, unlike most of their other posters at the meeting. I expect we will be hearing a lot more about biosimilars in the not too distant future, and the potential importance of this was highlighted by the intense popularity of Pfizer’s poster at the meeting.

Viewers of the ASCO 2013 preview video from Sally Church, PhD will have noted that PF-05280014 was one of her key breast cancer abstracts to watch out. If you haven’t already done so, here’s a link to the Pharma Strategy Blog ASCO 2013 Preview Video (free via sign-up) that is well worth watching.

Update June 5, 2013 5pm.  This post was not intended to be a comprehensive analysis of the biosimilar market and all the players (you have to pay me for that). However, Josh Berlin @BioPharmaJosh kindly pointed out on Twitter that the controversial Korean company Celltrion have filed for approval of their Herceptin biosimilar in Korea. This represents a competitive threat to Roche’s Asian market, and could give other companies a run for their money if they are first to market and file for approval elsewhere.


A standing room only audience at the recent annual meeting of the American Association for Cancer Research (AACR) heard from several distinguished speakers on what the future of cancer drug therapy is likely to look like: combinations of novel cancer agents.

This AACR session was one of the highlights of the meeting and would have merited from being part of the plenary program.

Jeffrey Engelman from MGH persuasively presented on why we need combination therapies to overcome resistance. He noted that:

  • Most cancers are not sensitive to currently available single-agent therapies
  • Even when sensitive to single-agent therapies, cancers develop resistance, often necessitating combinations

One of the challenges of this approach will be “identifying effective combinations,” he said.

Roy Herbst from Yale, presented on some of the practical challenges involved with the early phase testing of two drugs, and challenged the audience with a critical question:

“Do we possess the necessary translational tools that will help us identify the right drug combinations, ratios and schedules with the right patient?”

Stuart Lutzker from Genentech described their experiences of clinical trials with rational drug combination of trastuzumab and pertuzumab for HER2+ breast cancer.  He concluded that:

“Rational drug combinations have begun to yield exciting Phase III results and should be preferred over empiric drug combinations.”

The Pharma Strategy Blog video interview with Gordon Mills from ECCO/ESMO 2011 in Stockholm offers some interesting insights into how MD Anderson are helping to facilitate academia-industry combination trials with novel compounds from different companies in order to achieve more rational drug design and improve outcomes for people with cancer.

If two or more novel cancer drugs are required to interrupt key pathways or to avoid adaptive resistance, what does this mean for the regulatory strategy?

Janet Woodcock addressed some of these challenges in her AACR presentation, and discussed how the:

“FDA would not want to approve a combination regimen with two new agents unless each contributed to the effect.”

Draft guidance on “Codevelopment of Two or More Unmarketed Investigational Drugs for Use in Combination” was published by the Agency in December 2010. Click here for a PDF copy.

The document gives examples of a number of different phase II trial designs that can be used to demonstrate the contribution each drug makes to the combination, and the additive effect seen.

As an example, if each drug in a combination has activity and can be administered individually then the guidance document suggests a multi-arm phase II trial may be needed that compares the impact of either drug alone versus the combination and standard of care.  An adaptive trial may also be used if appropriate.

Dr Woodcock noted that future cancer drug development is likely to include increasing use of combinations, adaptive trials to evaluate various drug and diagnostic combinations and increasing attention to the use of novel biomarkers.

The message I took home from the AACR annual meeting is that the future of cancer therapy is in combinations, and we can expect more clinical trials with two unapproved agents (novel-novel combinations) in the future.

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