Cellular therapy just got real: Novartis is the first to get FDA approval for CAR-T treatment (Updated)

At $475,000, the therapy isn’t cheap but for its part, Novartis has said patients would only pay the full whack if they respond to the therapy by the end of the first month.

Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.


This post has been updated to include additional information including a Genentech drug approved to counter the CAR-T side effect cytokine release syndrome, a comment from NIH Director Francis Collins and the size of the patient population for Kymriah, the CAR-T therapy.

Novartis has secured FDA approval for its chimeric antigen receptor T cell  (CAR-T) therapy less than five months after submitting its biologics licensing application for priority review to the U.S Food and Drug Administration. The news is a game changer for the pharma industry as it marks a critical milestone in the development of CAR-T therapies.

The lead indication for Kymriah (previously known as CTL019) is for children and young adults with relapsed and refractory (r/r) B-cell acute lymphoblastic leukemia (ALL), which accounts for one-quarter of cancers diagnosed in children under 15.

The treatment is for people with the condition under 25 years old.

Novartis developed Kymriah through a partnership with the University of Pennsylvania which dates back to 2012. At the center of that partnership is the pioneer of this treatment, Dr. Carl June, Director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine. When that deal was finalized, June said in an interview with Bloomberg that he had never imagined that pharma companies would move into “ultra personalized therapy” and explained why they decided against developing a new company.

“We had lots of venture capital interest, but it’s hard to be a new company and it takes time to get set up. The fastest route to widespread availability is to use an existing company.”

Children’s Hospital of Philadelphia was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial, according to the news release.

Novartis Oncology CEO Bruno Strigini said in the release that Kymriah gives children and young adults a desperately needed option in their cancer treatment.

“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 program.”

At $475,000 a pop, the therapy isn’t cheap, but most people would consider that a small price to pay for a cure from a terrible, life-threatening disease. For its part, Novartis has said patients would only pay the full whack when patients respond to the therapy by the end of the first month, according to Marketwatch. The drug developer is working with the Centers for Medicare and Medicaid Services to initiate a pricing strategy.

Even so, Novartis currently estimates the patient population who would be eligible for Kymriah is 600 per year, making the initial pool for the treatment relatively scarce and worth less than $300 million, Reuters noted.

The procedure for using CAR-T is complex, illustrated by a description of the procedure:

Blood is first drawn from the patient and then sent to a specialized facility. There, the T-cells in the blood are isolated, activated, and engineered ex vivo to express either a chimeric antigen receptor (CAR) or a T-cell receptor (TCR), depending on the cancer target. To amplify the effect, the T-cell population is multiplied, creating an army of tumor assassins to dose back into the patient.

If the therapy is successful, the CAR-Ts will seek out and destroy cancer cells throughout the body, distinguishing them from healthy cells by the antigens they express.

Some details that underscore this complexity were highlighted by STAT.

Patients have to travel to one of 32 sites around the country to obtain the treatment. Doctors take patients’ white blood cells and ship them to Novartis facility in New Jersey where they’re edited and mailed back — a 22-day process. Despite the high price tag, it doesn’t include the expenses for travel, hospitalization, or any drugs used to counter Kymriah’s side effects.

The FDA also approved a Risk Evaluation and Mitigation Strategy for Kymriah. The program is intended to provide healthcare professionals with an informed understanding of the risks associated with the CAR-T treatment.

The news comes on the heels of Gilead Sciences’ $11.9 billion acquisition of Kite Pharma, which is developing a CAR-T treatment for non-Hodgkins lymphoma. The company is expected to apply for approval for the treatment later this year.

Additional indications for Kymriah are in the works both for the U.S. and EU. Novartis, in collaboration with Penn, has applications for the treatment of adult patients with r/r diffuse large B-cell lymphoma. It also plans to file applications for Kymriah in other markets in 2018, the company said in the statement.

On his blog, National Institutes of Health Director Dr. Francis Collins cautioned that despite the achievement, it is still early days and called attention to some of the serious side effects of the treatment.

Many questions must be addressed before we can herald immunotherapeutic approaches to cancer an unqualified success. There are still too many severe reactions, too many non-responses or relapses, and, potentially, a very high price tag for their widespread use, which will be truly challenging to scale up. But we’re off to a promising start.

On the subject of side effects, the FDA also approved Genentech’s treatment for a life-threatening side effect of CAR-T therapy — cytokine release syndrome (CRS).

The FDA granted the use of Actemra for CRS patients 2 years and older through an intravenous injection through priority review and gave it Orphan Drug Designation.

In clinical trials, Genentech noted in the release that “69 percent of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.”

The drug is something of a workhorse treatment for Genentech with several indications such as the treatment of the auto-immune disease giant cell arteritis approved earlier this year. It has also been approved for moderately to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juvenile idiopathic arthritis.

But even this treatment is not without risks, as a STAT article pointed out earlier this year.

Photo: Waldemarus, Getty Images