FDA approves first CAR-T cell therapy, giving rise to market forecast changes

Novartis has received approval for its chimeric antigen receptor T cell (CAR-T) therapy, Kymriah (tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, from the US Food and Drug Administration (FDA).

This represents the first approval of this form of gene transfer therapy and as such has given rise to the International Society for Cellular Therapy (ISCT), the global professional society of clinicians, researchers, regulatory specialists, technologists and industry partners in the cell therapy sector, revising its forecast for the CAR-T and cell therapy industries. This revised forecast encompasses the expected cross-industry reaction to the approval, and envisions the next stages in the development of cell therapies and the industry.

“At Novartis, we have a long history of being at the forefront of transformative cancer treatment,” said Joseph Jimenez, CEO of Novartis. “Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care.”

“We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical programme,” said Bruno Strigini, CEO of Novartis Oncology. “As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated.”

Kymriah is an immunocellular therapy and a one-time treatment for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (ALL) that takes the patient’s own T-cells and re-engineers them to fight cancer. The FDA approval of this therapy is based on the results of the Phase II ELIANA trial, which was sponsored by Novartis and included 25 centres in the US, EU, Canada, Australia and Japan.

“This therapy is a significant step forward in individualised cancer treatment that may have a tremendous impact on patients’ lives,” said Dr Carl June, the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine. “Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of haematologic and other cancer types.”

This milestone approval demonstrates the emergence of the cell and gene therapy sector rather than something that is still evolving for the future, according to the ISCT. The organisation forecasts that considerable investment will be made in the cell therapy field, particularly as there are other companies in the process of submitting applications to regulatory bodies for similar therapies.

“There are now upwards of 40 companies developing redirected T cells or NK cells for therapeutic use. There are also over 800 cell therapy clinical trials currently underway, and a considerable pool of research and pre-clinical work right across the cell therapy sector,” said Bruce Levine, PhD, ISCT Commercialization and Immuno & Gene Therapy Committees, Barbara and Edward Netter Professor in Cancer Gene Therapy, University of Pennsylvania Perelman School of Medicine. “International investment and grants are as critical for early research as it is for late-stage clinical development. The established path to commercialization taken by Novartis will provide considerable motivation for cell therapy scientists and development companies as well as investors looking to benefit from the ongoing success in the industry.”

“The Novartis approval is also a momentous milestone in the path for cell therapies reaching patients – the final objective of those of us involved in developing therapies,” said Catherine Bollard, President, ISCT and invited for the FDA Oncologic Drugs Advisory Committee Novartis CAR-T decision as an ‘invited subject matter expert’. “The approval for CTL019 (tisagenlecleucel) will increase the chance of, and potentially reduce the time for approval for treatments for other critical or fatal diseases with no alternative therapeutic option. ISCT will continue to drive to support all elements of the sector to make sure this happens.”

However, the organisation emphasizes that there are still challenges to overcome in the field of cell therapy. These challenges include commercialisation, market access, patient and physician adoption, cost/benefit discussions and reimbursement, as well as manufacturing scale up. A continuance of close collaborations is believed, by the ISCT, to be vital in overcoming these challenges.

“It is critical to have a realistic outlook and to have a measured response to the Novartis CAR-T approval. There are many important hurdles requiring different solutions for the industry in the short and long-term future. It will be several years before cell therapies are widely accessible for patients in more indications beyond leukaemia and lymphoma,” said Dr Miguel Forte, PhD, chief commercialization officer, ISCT and chief medical officer, Bone Therapeutics. “Solid tumours will fast become the next challenge for CAR-Ts and other cell and gene lymphocyte targeted immunotherapies. However, each hurdle will provide additional incentive, investment and know-how to progressively overcome the next. Now Novartis has proved it is possible for one therapy to succeed, this proves others will succeed too, and this adds competition to the mix. There is no bigger engine of development than competition.”

Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.