In the last day of 2016 I’d like to look at back and overview the most interesting events (in my opinion) and trends of the year. I’m going to split this overview for 2 parts without any particular order.
Results of pivotal CAR-T cell trials
Two major commercial developers of CD19 CAR-T cell therapies – Novartis and Kite Pharma, have reported results of pivotal trials, which will lay a foundation of market approvals in 2017 in US.
Novartis registration trial ELIANA in pediatric acute lymphoblastic leukemia (ALL) was conducted in 25 centers of few countries and evaluated 50 children. Complete response at 3 months was 82%. Relapse-free rate among responders was 60% at 6 months (49% survived with CR). Adverse events in a form of cytokine release syndrome were observed in 79% of patients (59% of which were admitted to the intensive care unit) and neurotoxicity – in 21%.
Kite Pharma conducted their registration CAR-T trial ZUMA-1 in patients with Non-Hodgkin Lymphoma (NHL) in 22 US centers. Complete response at 1 month was 47% (76% overall response), but dropped to 33% at 3 months. Severe cytokine release syndrome occurred in 20% of patients and neurotoxicity in 29%.
Both companies feel confident about obtaining market approval in 2017.
There were 7 market approvals of cell-based therapeutic products this year worldwide, but the most interesting, in my opinion, was Strimvelis. It is gene-modified autologous CD34+ cells for therapy of one of the forms of inherited severe combined immunodeficiency – SCID-ADA. The technology was developed by Italian scientists at San Raffaele Scientific Institute and licensed to Pharma giant GSK in 2010. This is the first ex vivo cell-gene therapy product, approved in Europe. Also, Strimvelis is first example of successful development of cell-gene therapy by big Pharma company, licensed from academic institution.
Because of orphan indication, Strimvelis was approved with only n=12, but demonstrated 100% efficacy (survival at 3 years and longer time point) in pivotal trial. The product is priced as 594,000 euros ($665,000 USD). Despite high price tag, the market size for Strimvelis is about 14 patients in Europe and 12 in US, therefore, the product will not be profitable for GSK. Intriguingly, Strimvelis is the first product in cell/ gene therapy history with “money back guarantee” policy.
Attempts to reform regulation in US
Debates about reforming regulation of cell-based therapies have been ongoing in US whole year. The first proposed controversial bill – REGROW Act triggered many discussions and split professionals for 2 camps. REGROW proposes to accelerate development cell of therapy products by skipping phase 3 of clinical trials and granting conditional marketing approval. Many professional organizations opposed REGROW. However, debates on REGROW recently faded away with passing another bill – Cures Act. It was giant “healthcare improvement” bill with few provisions for regenerative medicine/ cell therapy. As gentler alternative to REGROW, Cures Act gained more supporters, passed Congress and was signed by president into law. Read more about potential impact of Cures Act here.
Another historic event was FDA’s public hearing on clarification of some definitions, related to regulation of cell therapies. The field has never seen such big public interest and participation before. FDA received so many controversial comments about their cell therapy draft guidances, that 2-days hearing was necessary. There were many good points made during the hearing, highlighting necessity for education and open discussion between FDA and all stakeholders. FDA’s response in a form of final version of guidances is expected in the first half of 2017.
The end of StemCells Inc
This year, one of the oldest stem cell therapeutic company StemCells Inc ceased its operations. StemCells Inc was founded by Irv Weissman (Stanford U) and Fred Gage (Salk Institute) in 1988 and went public in 1992. Company was not able to deliver therapeutic promise over almost 3 decades of existence. Earlier this year StemCells Inc terminated Phase 2 of spinal cord injury trial, due to lack of efficacy. Poor financial performance (company went from $175 per share in 1995 to 57 cents per share in 2016), lack of trust from investors and some recent CIRM-related controversies also contributed to company’s setbacks. About a month ago, StemCells assets were acquired (through merger) by medical device company MicroBot Medical.
StemCells Inc shutdown is a big blow for the field, because it showed inability to deliver stem cell therapy promise, despite strong scientific foundation and financial support.
The biggest deals made in T-cell therapy space
2016 was a very good year for big deals in cell therapy. The most interesting and potentially impactful deals happened in engineered T-cell therapy space. Two more Biopharma companies entered CAR-T cell field – Baxalta (now part of Shire) and Regeneron. Baxalta (Shire) will pay up to $1.7B to Precision BioSciences for their gene editing platform in development of 6 allo- CAR-T cell therapy targets. Regeneron will collaborate with Adicet Bio on development of off-the-shelf CAR- and TCR- T-cell therapies. Another big deal (with $1B potential) was signed between bluebird bio and Medigen for development of TCR-modified T-cells.
Trend: big players are getting more and more interested in off-the-shelf T-cell therapies, watch how it will get hotter in 2017.
Stay tuned for part 2!