Biotech Strategy Blog

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

Posts tagged ‘CTL019 Chronic Lymphocytic Leukemia’

AACR Annual Meeting 2016 BannerOne of the hot topics at the forthcoming 2016 annual meeting of the American Association for Cancer Research (AACR) in New Orleans is likely to be CAR T cell therapy (Twitter: #AACR16).

Several research groups have shown impressive results in acute lymphoblastic leukaemia (ALL), but challenges remain in using adoptive cell therapy to treat other leukemias such as CLL, as we heard from Dr Porter at the recent BMT Tandem meeting. See post: Challenges and Opportunities of CAR T cell therapy in CLL. Perhaps more significantly, there’s a long way to go before CAR T cell therapies hit prime time in solid tumours.

What is fascinating is the pace of scientific research in the field. By the time the first CAR-T cell therapy is FDA approved, the second generation constructs used in them will most likely be obsolete.

This post reviews completely new research, which we’ve not written about before, that I expect we’ll hear more about at AACR, and discusses novel concepts about how to make CAR T cell therapy more effective in both leukemia and solid tumours.  It’s a good pre-AACR preparation for those interested in cancer immunotherapy and the emerging CAR T cell therapy landscape.

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Dr David Porter, U Penn

Dr David Porter, U Penn

Honolulu: The BMT Tandem meeting kicked off yesterday with an excellent plenary session on “CAR T Cell Therapy: CD19 and Beyond.” The three presenters were:

  • David Porter (University of Pennsylvania) CAR T cells for Leukemia
  • Martin Pule (UCL) Building a CAR
  • Michael Jensen (Seattle Children’s) CD19-Specific CAR T Cells as a Post-Allo HSCT Relapse Salvage Therapy

Dr Porter (pictured) is Director of the Blood and Marrow Transplant Program at the University of Pennsylvania. I spoke with him after his talk. This post gives a quick overview of some of the key points I took away.

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For many attendees, the most exciting news at the 2012 annual meeting of the American Society of Hematology (ASH) held last December in Atlanta was the prospect of personalized T cell therapy for the treatment of patients with B cell cancers such as chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL).

The potential of this new treatment option was recognized at ASH 2012 by the award to Dr Bruce R. Blazar, MD and Carl H. June, MD of the Ernest Beutler Lecture and Prize for research that generated major translational advances in T-Cell Infusions.

ASH 2012: Carl June, MD receives Ernest Beutler Prize

ASH 2012: Carl June, MD receives Ernest Beutler Prize

Dr June, in his accompanying lecture discussed preliminary data for the trial of CTL019 (formerly CART-19), a novel chimeric antigen receptor-transduced T cell therapy against CD19. Subscribers to premium content can login to read more below:

In the 12 patients (10 adults CLL and 2 children with ALL) who have received CTL019, the responses have been extremely promising with a clinical response (CR+PR) seen in 9 out of the 12.

There have already been several reports in the media about this trial with many news outlets reporting that one of the children with ALL had been “cured.” That this treatment has tremendous potential is undisputed, but in my view it is a case of “hype over hope” at this stage to say that anyone has been cured in the absence of long-term follow up over at least five years.

In August 2012, Novartis announced they had formed an alliance with the University of Pennsylvania and had obtained a worldwide license to commercialize CART-19 (now CTL019). In December 2012, Novartis purchased a NJ manufacturing facility from Dendreon for $43M that will used for the production of personalized immunotherapy.

Novartis, through their recent acquisition of the Dendreon facility in NJ, are fortunate to gain access to the technology, state-of-the-art tracking system that matches the product to each patient, as well as the Good Manufacturing Practices (GMP) that were pioneered in the production of sipuleucel-T (Provenge).

In the immediate future, Novartis and U Penn have the challenge of showing that the dramatic results seen in some of the initial patients are reproducible in a larger trial and also at institutions other than Penn.

ASH 2012 Carl June Ernest Beutler Prize LectureIn his ASH lecture, Dr June noted that there are side effects and toxicities associated with CTL019 including tumor lysis syndrome (TLS), and Cytokine Release Syndrome (CRS) was seen in all patients.

This suggests it is unlikely this therapy will be used outside of the hospital setting.  In the United States, I would not be surprised to see it only used at hematology transplant centers, where there is the necessary expertise to deal with both the process and any complications that arise. Novartis may end up with a high priced therapy targeted at a small niche market.  It will be interesting to see the commercial strategy that Novartis decide to adopt.

I expect we will hear a lot more about chimeric antigen receptor technology in 2013. Personalized immunotherapy is a complex topic and one that will require significant investment in medical education by Novartis if a broader audience is the intended target. Dendreon failed miserably at launch in explaining how sipuleucel-T (Provenge) worked and did not convince large numbers of medical oncologists that their immunotherapy worked.  Even to this day, there remains considerable sceptism amongst that physician segment.

If you would like to know more about the science behind CAR therapy and it’s potential in hematology, Sally Church, PhD (who co-launched Gleevec in the US while at Novartis Oncology) will be offering insights in a monthly newsletter to be launched soon. Check out Pharma Strategy Blog for more information.

 

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