Biotech Strategy Blog

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

Posts tagged ‘Dendreon’

Last night Luke Timmerman of Xconomy posted a nice article on the formation of a new Seattle startup, Juno Therapeutics, which aims to develop the chimeric antigen receptor therapy (CART) based on autologous T cells developed by Memorial Sloan Kettering (MSK) in New York, Fred Hutchinson Cancer Center (FHCC) and the Seattle Children’s Hospital, both in Seattle.

Juno secured $120M in Series A funding, which is pretty good for a two month old startup and shows how much excitement there is for this exciting technology.

How does this new development impact the CART landscape and in particular, the U Penn and Novartis partnership?

There has been a lot of negative publicity around Dendreon and sipuleucel-T (Provenge) recently, and the lack of a clear mechanism of action remains a concern to many.

Irrespective of the company’s commercial performance, sipuleucel-T remains an FDA approved therapeutic cancer vaccine that provides a benefit to some patients.  It provided a proof-of-concept that immunotherapy can offer a survival advantage, albeit for a median of 4.1 months in asymptomatic advanced prostate cancer.

Dendreon is learning the hard way the failings in its commercial strategy, and no doubt these will be absorbed by others with other therapeutic vaccines in development.

Which brings me to an interesting paper published online first on November 8, 2011 in the American Association for Cancer Research journal, Clinical Cancer Research.


Researchers from the National Cancer Institute (NCI) published data from a small pilot trial showing a clinical response to a poxviral vaccine (PANVAC) in metastatic breast cancer and ovarian cancer patients.

Twenty six patients were in involved in the pilot NCI trial with PANVAC, a recombinant poxviral vaccine expressing the tumor-associated antigens (TAA), carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).

The results showed a median overall survival of 13.7 months in the 12 breast cancer patients with four patients having stable disease, and one patient on study for 37 months.  One patient had a 17% reduction in mediastinal mass.

In ovarian cancer, median overall survival for the 14 patients treated was 15.0 months.

This is promising early stage data in very sick patients. Mahsa Mohebtash and colleagues conclude in their paper that:

“Some patients who had limited tumor burden with minimal prior chemotherapy seemed to benefit from the vaccine. Further studies to confirm these results are warranted.”

Immunotherapy holds a lot of promise.  Research suggests that cancer vaccines once they have provoked a response may improve a patients’ response to subsequent therapies through enhanced T-cell response.

The NCI researchers in their paper noted that time to progression and tumor shrinkage may not be good endpoints for evaluating immunotherapies given that it can take a few months for the optimal result after vaccination and there is often little impact on the tumor size, as judged by classical RECIST measurement.

Instead, overall survival (OS) should be considered a more relevant endpoint.  Sipuleucel-T failed to show a benefit in progression free survival (PFS), but did show an impact on OS. In prostate cancer, OS remains the gold standard for regulatory approval, which is why Exelixis recently took a hit for not making this the primary endpoint in their phase III trial (306) for cabozantinib (XL184).

There are several challenges to consider with vaccine therapies:

  • How do we identify upfront which patients are most likely to respond to the vaccine?
  • The ideal setting is likely to be adjuvant rather than metastatic disease, but these trials will take a very long time and significant funding to come to fruition.
  • Cancer vaccines may allow some patients to live longer, but they have yet to show any meaningful benefit in other clinical measures such as bone pain, symptoms etc.
  • There are fewer side effects, but how do we evaluate how well patients are doing without clinically validated surrogate markers to aid in assessment?

This early research with a vaccine in breast and ovarian cancer, albeit on a very small number of patients, adds further support to the notion that vaccines may offer treatment benefits in the future.

We still, however, have a long way to go in understanding how best to use immunotherapy effectively and incorporate it into clinical treatment guidelines.  We should also be wary of false hope and hype – I look forward to following the progress of PANVAC going forward.

ResearchBlogging.orgMohebtash, M., Tsang, K., Madan, R., Huen, N., Poole, D., Jochems, C., Jones, J., Ferrara, T., Heery, C., Arlen, P., Steinberg, S., Pazdur, M., Rauckhorst, M., Jones, E., Dahut, W., Schlom, J., & Gulley, J. (2011). A Pilot Study of MUC-1/CEA/TRICOM Poxviral-Based Vaccine in Patients with Metastatic Breast and Ovarian Cancer Clinical Cancer Research, 17 (22), 7164-7173 DOI: 10.1158/1078-0432.CCR-11-0649

With the collapse of the Dendreon share price today following poor sales data (Adam Feuerstein on The Street has an excellent write up about this), attention has again focused on the prostate cancer market.

Zytiga (abiraterone acetate) was recently approved by the European Medicines Agency (EMA), following FDA approval earlier this year.

The EMA Committee for Medicinal Products for Human Use granted the marketing authorization for Zytiga at it’s July 2011 meeting.  The approval noted,

“The poor prognosis of the target patient population represents a high unmet medical need while the novel mechanism of action of abiraterone has the potential to offer an alternative therapeutic option for these patients.”

What does this mean for sales of sanofi-aventis’ cabazitaxel (Jevtana), which was approved in Europe earlier this year?

Given that both drugs have approval in the same indication for metastatic castrate resistant prostate cancer (mCRPC) post-docetaxel chemotherapy, and the price is likely to be comparable, my guess would be that Jevtana sales will take a big hit.

After a sick prostate cancer patient has undertaken several cycles of chemotherapy with docetaxel, why would they not want to take an oral pill as opposed to another chemotherapy drug, which does have a less than stellar adverse-event profile.  The answer is they will probably take a chemo-holiday and use Zytiga.

Jevtana simply came to the market too late in Europe, and Zytiga gained accelerated approval.  It’s a reminder that we live in a dynamic pharmaceutical market place, as the news last night from Dendreon has also reminded us.

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