Biotech Strategy Blog

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

Posts tagged ‘Novartis CTL019’

That’s the $64K question we all want to know, and what’s more is gene editing necessary when it comes to creating an “off-the-shelf” T cell therapy, which instead of modifying a patient’s own T cells (autologous), uses cells from a healthy donor (allogeneic)?

We were really curious too, and sought out one of the world’s leading experts for their opinion on this very issue.

Subscribers can login to read more, along with our analysis of the potential impact of this latest news on CAR T cell therapies.

Directions to Cellectis in ParisCellectis is a Paris based biotechnology company, (NYSE alternext: ALCLS.PA) with an aspiring “blue ocean” strategy that, if successful, could revolutionize cancer immunotherapy.

The potential of using engineered T-cells (known as chimeric antigen receptors) to fight cancer was highlighted by the impressive data presented at last year’s annual meeting of the American Society of Hematology (ASH 2013).

To many, the data for the U Penn/Novartis engineered T-Cell therapy (CTL019) in pediatric acute lymphoblastic leukemia (pALL) was worthy of presentation in the plenary session at the meeting.

Over the past year, investors have poured money into companies active in the field: we’ve written about the launch of Juno Therapeutics and their intellectual property (IP) dispute with Novartis. More recently Kite Pharma had a successful IPO.

Why was Biotech Strategy Blog keen to interview Cellectis Chief Scientific Officer (CSO) Philippe Duchateau, PhD and Chief Executive Officer (CEO) André Choulika, PhD (picture left and right respectively)?

ellectis CSO CEO

The answer is they have a completely new and innovative approach to CAR-T cell therapy that in the long run could be a “game changer.” Their lead product (UCART19) is an allogeneic CAR T cell for ALL and CLL. Allogeneic means the T cells that are modified come from a donor. This is in contrast to the autologous approaches that Kite, Novartis and Juno are developing where the engineered CAR-T cells come from the patient themselves.

All credit to Pfizer for seeing the potential in a company that has been on our radar for a while. They recently announced a major collaboration with Cellectis that could turn both Cellectis and Pfizer into major players in the cancer immunotherapy space.

In this fast moving R&D space there are already signs of where competition to Cellectis may come from, and it’s not Novartis, Juno or Kite.

Subscribers and those with an interest in CAR-T cell immunotherapy can login to read more, including excerpts of the interview at Cellectis HQ in Paris:

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A regular reader of BSB wrote in asking for an update on Amgen’s blinatumomab, an anti CD3/CD19 bispecific antibody being investigated in B cell adult acute lymphoblastic leukemia (B-ALL) and Non Hodgkins Lymphoma (NHL). It has orphan designation for both indications.

Amgen acquired Micromet and their BiTE program way back in January 2012. At the time, the R&D head, Roger Perlmutter, referred to the exploratory phase II results as being a key driver for their interest in the technology. Like many, I too, was initially enthusiastic about the bispecific antibody when it was with Micromet, since those were very encouraging results in refractory adult ALL, a particularly hard to treat malignancy with a generally poor prognosis.

Unfortunately, since then we’ve heard very little about the program, which seems to have languished in the Amgen portfolio, a not uncommon occurrence when big Pharma/Biotech take over small biotech programs. In the meantime, chimeric antigen receptor (CAR) T cell therapies have arrived to much fanfare, and with it, even more dramatic results that have caught people’s attention.

Is there still a future for blinatumomab and BiTE technology?

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The Inquirer yesterday reported on Philly.com that start-up Juno Therapeutics (Juno) are now in control of a legal dispute between St Jude Children’s Hospital (St Jude) and the University of Pennsylvania (Penn) over chimeric antigen receptor (CAR) intellectual property that contributed to the development of CTL019, licensed by Penn to Novartis. Thanks to @lomu_j for sharing this news on Twitter.

According to the Inquirer, last month Juno entered an agreement with St Jude to commercialize their CAR T-cell technology, which gave them the right to “control, pursue and defend” the dispute between Penn and St Jude.  On December 18, Juno’s intervention was approved in Federal District Court in Philadelphia.

(Update Jan 10: Zack Seward (@ZackSeward) provides additional commentary on WHYY Philadelphia newsworks on “The high-stakes legal fight over a ‘cancer cure from Penn.’ He reports that St Jude have every confidence in their patent.

 

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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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