A team of outside experts convened on Wednesday morning to determine the pros and cons of one of the most exciting new drug modalities to ever hit biotech: chimeric antigen receptor T-cell (CAR-T) therapies.
The subject of the industry’s collective gaze was CTL019 (tisagenlecleucel), developed by Swiss pharma company Novartis. It didn’t disappoint.
The 10-person panel (one expert had to step out before the vote) unanimously recommended FDA approve CTL019 for children and young adults with relapsed and refractory (r/r) B-cell acute lymphoblastic leukemia (ALL).
ALL accounts for around 25 percent of all cancers diagnosed in patients under the age of 15. For the r/r cohort, survival rates plummet to around 16-30 percent given the lack of treatment options.
By comparison, CTL019 brought a majority of patients into remission.
The case for the therapy was based in part on the results of a Phase 2 study called ELIANA. Data show some 82 percent of patients (41 out of 50) infused with the engineered CAR-T cells had achieved either complete remission or complete remission with incomplete blood count recovery at the three-month-mark.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
In a brief statement sent by a Novartis spokesperson, the pharma company thanked the panel and all participating patients for today’s decision:
“Novartis has long believed in the potential of chimeric antigen receptor T cell (CAR-T) therapies to change the cancer treatment paradigm, and we thank the FDA ODAC [Oncologics Drug Advisory Committee] for its recommendation, and extend our deepest gratitude to the patients and families who have participated in our clinical trials to advance this important research.”
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CTL019 traces back to the seminal work of Carl June at the University of Pennsylvania’s Perelman School of Medicine. Novartis acquired the program through a 2012 partnership as excitement around the technology began to build.
The fervor hasn’t dissipated over the last five years, as captured by one of Wednesday’s expert panelists Tim Cripe, an oncologist from the Nationwide Children’s Hospital in Columbus, Ohio.
“I think this is the most exciting thing I have seen in my lifetime,” he declared, as the publicly-broadcast session wrapped up.
While the discourse was optimistic throughout, no one is expecting a straightforward launch for such a complex process. A large part of the session was dedicated to manufacturing challenges and whether Novartis would be able to deliver a reproducible product when working at scale.
To that end, it has chosen 30 sites nationwide to perform the autologous transplant.
Blood will be drawn from the patient at those clinics and then sent to a specialized manufacturing facility. There, the T-cells in the blood are isolated, activated, and engineered ex vivo to express a specific chimeric antigen receptor (CAR) that can bind CD19, a protein expressed by B-cells. To amplify the effect, the T-cell population is multiplied, creating an army of tumor assassins. That live product is sent back to the clinic to be reinfused into the patient.
If the therapy is successful, the CAR-Ts will seek out and destroy cancerous B-cells throughout the body, identified through their expression of CD19.
Even when the therapy works as intended, potentially fatal toxicities can occur. Close to half (48 percent) of patients in the ELIANA study experienced cytokine release syndrome (CRS) severe enough to be recorded as a Grade 3 or Grade 4 adverse event.
Based on the panel’s unanimous vote, it seems the risks are still worth the reward. FDA is not obliged to follow suit — though it almost always does, especially when the decision is so clear-cut.
An official yay or nay is expected by October 3. An expert decision on another CAR-T therapy, manufactured by Kite Pharma, is expected later this year.
Photo: royaltystockphoto, Getty Images
