FDA Committee Recommends Approval for Novartis’ CAR-T Cell Therapy for Acute Lymphoblastic Leukemia
Nicole Watkins FDA News, Oncology Comments Off on FDA Committee Recommends Approval for Novartis’ CAR-T Cell Therapy for Acute Lymphoblastic Leukemia
Basel, July 12, 2017 – Novartis announced today that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and youthfull adult patients with B-cell acute lymphoblastic leukemia (ALL).
“The panel’s unanimous recommendation in favor of CTL019 moves us closer to potentially delivering the first-ever commercially approved CAR-T cell therapy to patients in need,” said Bruno Strigini, CEO, Novartis Oncology. “We’re very proud to be expanding fresh frontiers in cancer treatment by advancing immunocellular therapy for children and youthful adults with r/r B-cell ALL and other critically ill patients who have limited options. We look forward to working with the FDA as they accomplish their review.”
Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under fifteen years old and is the most common childhood cancer in the US[1]. Effective treatment options for patients with r/r ALL are limited. In pediatric and youthful adult patients with B-cell ALL that have relapsed numerous times or become refractory to treatment, the five-year disease-free survival is less than 10-30%[Two],[Three],[Four].
The ODAC recommendation is based on review of the CTL019 r/r B-cell ALL development program, which includes the Novartis-led ELIANA investigate (NCT02435849), the very first pediatric global CAR-T cell therapy registration trial. Findings from a US multicenter trial and a single site trial examining the safety and efficacy of CTL019 among pediatric and youthfull adult patients with r/r B-cell ALL also supported the recommendation and the Biologics License Application (BLA)[Five].
CTL019 was very first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Children’s Hospital of Philadelphia (CHOP) was the very first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.
“It is encouraging to see the FDA panel’s recommendation and continued momentum behind this innovative therapy, which has potential to help youthfull patients with relapsed/refractory B-cell ALL,” said the Penn team’s leader, Carl June, MD, the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn. “We look forward to continuing to work with Novartis to help make a lasting influence on the way this disease is treated.”
“We know firsthand from treating children and youthfull adults with relapsed/refractory B-cell ALL that they despairingly need innovative medicines that provide a fresh treatment to managing this aggressive disease,” said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, Director of the Cancer Immunotherapy Frontier Program and Chief of the Section of Cellular Therapy and Transplant at CHOP. “Today’s vote in favor of CTL019 is a positive step and we appreciate Novartis’ commitment to pediatric patients.”
Earlier this year, Novartis submitted a BLA for CTL019 to the FDA, marking the very first obedience by Novartis for a CAR-T cell therapy. CTL019 previously received FDA Breakthrough Therapy designation and is under Priority Review by the FDA. The FDA will consider the vote as it reviews the BLA, albeit it is not obligated to go after the recommendation. Novartis resumes to invest in the necessary infrastructure for the potential commercialization of CTL019, including manufacturing and the establishment of a network of certified treatment centers.
Novartis plans extra filings for CTL019 in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA) for the treatment of adults with r/r diffuse large B-cell lymphoma (DLBCL).
About CAR-T and CTL019
CAR-T is different from typical petite molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the manufacturing facility to create T cells that are genetically coded to express a chimeric antigen receptor to recognize and fight cancer cells and other B-cells voicing a specific antigen.
ELIANA (NCT02435849) is the very first pediatric global CAR-T cell therapy registration trial, with explore enrollment having occurred across twenty five centers in the US, Canada, EU, Australia and Japan.
Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through cautiously managed and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no ensure that CTL019 will ever be commercially available anywhere in the world.
About CTL019 Manufacturing
The Novartis leukapheresis process using cryopreservation permitted for manufacturing and treatment of patients from around the world. Cryopreserved leukapheresis involves removing white blood cells from a patient’s blood and preserving them at very low temperatures. Cryopreserved leukapheresis gives physicians the plasticity to schedule apheresis at a time that is in the best interest of their patients. Novartis commercial manufacturing for CTL019 resumes to build on its practice in its Morris Plains, Fresh Jersey facility, which has already manufactured CTL019 for hundreds of patients in global clinical trials. Novartis believes that practice is significant in cell therapy manufacturing, and the practice gained at the Morris Plains, Fresh Jersey facility will be a foundation for commercial manufacturing of CAR-T therapies. Novartis has made and resumes to make investments in manufacturing.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.Five billion, while R&D across the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately one hundred fifty five countries around the world. For more information, please visit http://www.novartis.com.
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact [email protected]
[1] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute, April 2013; Section 28.9 (12).
[Two] Oudot, C. Auclerc, F. Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE ninety three Examine. Journal of Clinical Oncology, March 2008; Volume twenty eight (9).
[Trio] Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003; one hundred twenty three (Three).
[Four] Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and adolescents with a 2nd or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Examine Group. Journal of Pediatric Hematology/Oncology. July 2013; thirty five (Five).
[Five] Novartis CTL019 ODAC Briefing Document.