Since 2017, when Novartis’ Kymriah was first to the FDA finish line for a CAR-T treatment and was followed seven weeks later by Gilead Sciences' Yescarta, the companies have developed an intriguing back-and-forth as they pursue cell therapy breakthroughs to treat lymphoma.
Wednesday, Novartis made a key gain as it reported positive data from a trial of Kymriah in patients with relapsed or refractory follicular lymphoma.
Of the 97 patients who received one infusion of Kymriah in the Elara trial, 86% responded and 66% achieved a complete response after a median follow-up of 11 months. But more importantly, according to Novartis, no patients experienced grade 3 or 4 cytokine release syndrome, the most common side effect associated with CAR-T therapy. Grade 1 or 2 cytokine release syndrome occurred in 49% of patients.
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While three patients died from progression of the disease, there were no fatalities from treatment, Novartis said. Grade 1 or 2 neurological events occurred in 9% of the patients. One patient who experienced grade 4 neurological events recovered.
In addition, investigators observed a strong response in heavily pre-treated patients with a critical need for a treatment option.
The findings "suggest Kymriah may play an important role in the third-line treatment of relapsed or refractory follicular lymphoma,” said Stephen Schuster, M.D., of the University of Pennsylvania’s Perelman School of Medicine. Schuster will present his findings Monday during a virtual meeting of the American Society of Clinical Oncology.
Novartis plans regulatory submissions based on the Elara trial this year.
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Gaining approval for Kymriah in this indication would put Novartis in position to play catch-up against its CAR-T rival. Yescarta won approval for relapsed or refractory follicular lymphoma in March.
Yescarta won the sales battle between the two last year, earning $563 million to $474 million for Kymriah.
The rivalry has featured a series of punches and counterpunches. After Kymriah won an approval for acute lymphoblastic lymphoma in August of 2017, Yescarta followed in October with an approval for large B-cell lymphoma. Seven months later, Kymriah countered with a nod of its own for large B-cell lymphoma.
A third CAR-T competitor is a latecomer to the party. After regulatory setbacks, Bristol Myers Squibb finally earned approval for Breyzani for relapsed or refractory large-B cell lymphoma in February.
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Cracking follicular lymphoma could be particularly rewarding. The disease, once considered “incurable,” according to Novartis Chief Medical Officer John Tsai, M.D., is the second most common form of lymphoma, accounting for 22% of diagnoses. Tumors start slowly then become more aggressive over time, making them more resistant to treatment. But CAR-T therapy has provided hope.
“Patients with follicular lymphoma who do not respond to their current treatment or who relapse early after treatment often have to endure multiple treatments, which can result in diminished clinical outcomes with each successive therapy,” Schuster said in the release. "Our goal as researchers is to continue to explore the potential of CAR-T therapy."