Biotech Strategy Blog

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

Posts tagged ‘CTL019 CLL’

One of the benefits of attending the American Society of Hematology (ASH) annual meeting that finished earlier this week in New Orleans is the opportunity to talk to experts who are at the forefront of their field.

Picture of Dr Renier Brentjens, Director of Cell Therapeutics, Memorial Sloan-Kettering Cancer Center

Picture Credit: MSKCC

Renier Brentjens, MD PhD,  is Director of Cell Therapeutics at Memorial Sloan-Kettering Cancer Center (MSKCC) and one of the scientific founders of Juno Therapeutics (Juno), a start-up company that recently raised $120M in Series A financing.

Luke Timmerman wrote about the company launch on Xconomy and you can read the Dec 4 press release from Juno here.

juno-therapeuticsLike a modern day David versus Goliath, Juno Therapeutics has set itself up to compete with Novartis in the exciting world of chimeric antigen receptor (CAR) modified T cell therapy that has already shown dramatic results in pediatric and adult acute lymphoblastic leukemia (ALL).

A lot of media attention has focused on the Novartis collaboration with the University of Pennsylvania to develop a novel therapy using CAR modified T cells (CART-19/CTL019) that can be directed against tumor cells that express the CD19 antigen.

The potential promise of CAR modified T cell therapies has already led to a flurry of law suits between the St Jude Children’s Hospital (St Jude) and University of Pennyslvania (U Penn).

According to the Daily Pennsylvanian, U Penn are seeking to invalidate a St Jude patent while St Jude have claimed violations of the terms of a material transfer agreement that allowed access by Carl June (U Penn) to work done by Dario Campana (St Jude).

It will be interesting to see what intellectual property Novartis actually owns and whether they did a thorough enough due diligence prior to licensing the rights to CTL019 from U Penn.

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New Orleans – the hematology diehards were up early yesterday for the 7.30 am oral session on some of the most interesting data at the annual meeting of the American Society of Hematology (ASH) on potential new treatments for Chronic Lymphocytic Leukemia (CLL).

Just to make sure everyone’s Fitbits were well exercised, the organizers put the session in the farthest end of the Convention center! Like many of the CLL sessions, it was a full house with multiple financial analysts sitting in the row behind me taking copious notes and pictures.  Unlike at ASCO, there is no virtual meeting, so you can’t replay any of the oral scientific sessions at a later date. If you didn’t see it, you missed it! There’s no substitute for boots on the ground.

What this post is about is my subjective opinion and top-line impressions of the information presented and some of the key strategic issues and challenges that came across listening to a full presentation of the latest data. I’m not going to rehash the press releases and the abstract data, most readers have already assimilated that.

It is what it says — notes from the road — the kind of things I’d write in a trip report if I were in a company.

The four presentations covered in this post are:

Abstract 871: Dinaciclib (SCH 727965) Is a Novel Cyclin-Dependent Kinase (CDK) Inhibitor That Exhibits Activity In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia (CLL).

Abstract 872: Bcl-2 Inhibitor ABT-199 (GDC-0199) Monotherapy Shows Anti-Tumor Activity Including Complete Remissions In High-Risk Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL).

Abstract 873: Randomized, Phase II Dose Optimization Study Of Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) In Patients With Relapsed, Refractory CLL.

Abstract 874: Phase I Trial Of Autologous CD19-Targeted CAR-Modified T Cells As Consolidation After Purine Analog-Based First-Line Therapy In Patients With Previously Untreated CLL.

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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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