The FDA has cleared an IND application to Servier to set sail in clinical development of UCART19, an allogeneic CAR-T cell therapy developed by Cellectis.
The French company Cellectis is developing off-the-shelf CAR-T therapies for cancer. Hot on the heels of its rival Celyad, the company was now granted FDA clearance to start clinical development of UCART19 in the US under the guidance of Servier.
In November 2015, Servier acquired exclusive worldwide rights to further develop and commercialize Cellectis’ lead product UCART19 in a huge €35.8M deal, which could reach more than €300M in milestone payments. In addition, Pfizer and Servier have entered into an exclusive global license and collaboration agreement to co-develop and commercialize UCART19.
UCART19 is an allogeneic CAR-T cell product being developed for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia (B-ALL). In this allogeneic setting, T cells are sourced from a healthy donor instead of using the patients own cells and then engineered using the TALEN technology. This allows for reduced production times and off-the-shelf available CAR T cells – but it also comes with higher risks of immunogenicity.
Servier has already been cleared by the EMA for the first European phase I trial for UCART19 in 2016. The CALM study is currently running in the UK testing the safety, tolerability and antileukemic activity of UCART19. With the current IND clearance by the FDA, the CALM study will be expanded to include several centers in the US, including the MD Anderson Cancer Center in Houston (Texas).
Cellectis has been in the headlines with its first-in-human use of UCART19 in patients suffering from aggressive leukemia, where the therapy was able to save the lifes of two babies. However, one of the babies also suffered from graft versus host disease (GvHD) — a big worry with off-the-shelf approaches.
The competition within the CD19-specific CAR-T cell field is large and so are the risks of failing. This situation has become very clear with the recent termination of Juno Therapeutics‘ lead CAR-T program, which has caused a total of five deaths. Novartis and Kite Pharma are currently leading the field and have both completed phase II trials with their CAR-T candidates targeting CD19.
Cellectis’ key rival Celyad has also just been cleared by the FDA to investigate its NKR-2 CAR-T cells in the US. These cells express a Natural Killer cell receptor and are being investigated in seven indications including five solid cancers and two hematological malignancies.
CAR-T therapy is a hot topic in the cancer field these days. You can read more about its opportunities and challenges in our recent review.
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