March 30, 2017
By Mark Terry, BioSpace.com Breaking News Staff
In the race to get a CAR-T therapeutic to the market, Swiss-based Novartis is now officially leading the pack. The company announced yesterday that the U.S. Food and Drug Administration (FDA) had accepted its Biologics License Application (BLA) filing and granted priority review for CTL019 (tisangenlecleucel-T).
Chimeric antigen receptor T cell (CAR-T) therapy is a fairly laborious therapy. Basically, blood is drawn from the cancer patient and sent to the company, which is likely to have a specialized facility for the process. The T-cells, a type of immune cell, are isolated and engineered to express a chimeric antigen receptor (CAR) or a T-cell receptor (TCR), based on the type of cancer being targeted. Then the population of T-cells is multiplied, and returned to the physician, who will administer them to the patient. The CAR-T cells, having been programmed specifically for the cancer, destroy the cancer cells while ignoring the healthy cells.
In clinical trials, it’s been highly successful, but has also led to several patient deaths, most notably in multiple clinical trials run by Juno Therapeutics . Juno’s problems left Novartis and Kite Pharma ahead in the race for a marketable product.
Juno, for its part, has abandoned its troublesome JCAR015 program to focus on another CAR-T program, JCAR017 for diffuse large B cell lymphoma. Kite is focused on non-Hodgkin’s lymphoma and is planning a first-quarter submission for its own BLA, which would pretty much mean this week.
Novartis has indicated that it is also planning additional filings in the US and Europe later this year, as well as a BLA with the FDA in adults with r/r diffuse large B-cell lymphoma (DLBCL) and marketing authorization with the European Medicines Agency in r/r B-cell ALL and r/r DLBCL.
Novartis noted that 48 percent of the patients in the ELIANA clinical trial had grade 3 or 4 cytokine release syndrome (CRS), which is a potentially lethal side effect to CAR-T therapies. The most severe cases are called cytokine storms. They result in a systemic inflammatory response similar to those seen in severe infections, basically acting like a non-infective fever, and can cause pulmonary edema, which is what killed most of the patients in Juno’s trial fatalities.
In a statement, Novartis said, “CRS was managed per protocol on a global scale using prior site education with implementation of the CRS treatment algorithm. There were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events including confusion, delirium, encephalopathy, agitation and seizure. No cerebral edema was reported and no grade 4 neurological and psychiatric events were observed.”
On the other hand, the therapy can be extremely effective in difficult-to-treat cases. “Even if a patient has difficult-to-treat relapsed/refractory leukemia, we have seen treatment with CTL019 in clinical trials put cancer into remission,” said Stephan Grupp, director of the Cancer Immunotherapy Frontier Program and director of Translational Research for the Center for Childhood Cancer Research at the Children’s Hospital of Philadelphia (CHOP), in a statement. “This could be a first-of-its-kind treatment with exciting potential to help pediatric and young adult r/r B-cell ALL patients.”
With likely approval in the next six months, attention is turning to pricing. Although some analysts have suggested the price for the CAR-T therapy will start at $250,000, David Nierengarten, with Wedbush, wrote, “We note to justify the current market capitalization, we would require either a price point of $500,000 per course or up to 50% market share (or some combination), both of which, while possible, we believe is less likely.”
Because of the labor-intensive aspects of CAR-T therapies, with patients being treated on an individual basis with their own blood samples being engineered for them at a separate facility, the price is likely to stay high. But, as John Carroll, writing for Endpoints News, says, “Whoever gets onto the market first will have a big edge in setting the price for these first wave drugs.”
