CAR-T therapies have emerged as a hot topic at the recent BIO and ASCO meetings, and for good reason: They’ve produced sky-high efficacy numbers in patients lacking other therapy options and even talk of curative potential. That’s despite the concerns around issues like potentially dangerous side effects and costs.
But beyond the sexier aspects of CAR-T cells lie some issues that experts at the two conferences said remain to be hashed out, especially in terms of infrastructure and ensuring everybody on the clinical side knows what they’re doing.
In an interview at the recently concluded ASCO meeting in Chicago, Mark Levis, who heads the leukemia program at Johns Hopkins University, said the problem with CAR-T is that the infrastructure has not quite matured. For example, administering CAR-T – which he said nobody enjoys doing at his center – requires having a local graft engineering laboratory, as well as doctors and nurses who know how to administer the therapy and handle the toxicity. The procedure simply hasn’t been integrated into the culture yet, he said, comparing it to bone marrow transplant, which has since become established at many hospitals but still took decades to catch on.
Indeed, the complexity around the clinical side of things has been part of why adoption of CAR-T has been slow, said Nina Bauer, associate director for cell therapy commercial development at Swiss contract manufacturer Lonza, which is handling part of the manufacturing process for bluebird bio’s trial of bb2121, a CAR-T for multiple myeloma. The Food and Drug Administration approved Novartis’ Kymriah last August for pediatric acute lymphoblastic leukemia (ALL), followed by Gilead Sciences’ Yescarta – which it acquired when it bought original developer Kite Pharma for $11.9 billion – in October for diffuse large B-cell lymphoma (DLBCL) in adults. Kymriah also won approval for DLBCL last month.
The challenge is knowing how to draw a sample, perform the necessary upstream manipulation at the hospital and then provide manufacturers with enough starting material to make the therapy. While she did not have specific numbers, the frequency by which manufacturers receive samples insufficient for manufacturing the product is greater than people think, Bauer said.
In December, Bloomberg reported that two months after Yescarta’s approval, only five patients had received it, largely because of reimbursement hurdles. Meanwhile, Novartis said in its latest quarter earnings that Kymriah had sales of $12 million, at a list price of $475,000 per treatment in ALL.
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.
Yet, manufacturing and logistics can be issues as well.
A big question is whether the manufacturers can handle the volume that will come as therapies move into increased commercial development, said Sharon Karlsberg, principal at Evanston, Illinois-based consultancy ZS. That’s especially crucial when dealing with fast-acting cancers like pediatric ALL and DLBCL, where patients don’t have the luxury of waiting three weeks for their completed therapy to come back to the clinic, she said. For this reason, she said, bispecific antibodies could also be competitive, given that they lack CAR-T therapies’ time constraints, not to mention allogeneic CAR-T therapies that don’t require harvesting the patient’s own cells, like the ones French drugmaker Cellectis is developing.
One solution, said, would be to have CAR-Ts manufactured at the point of care rather than centrally. However, while that would help to cut down costs and time, it would also raise concerns about product consistency. At the same time, Bauer said that about 30 percent of the cost of CAR-T therapies comes from quality-control analytics, with some cost estimates running as high as 50 percent. Yescarta’s list price in DLBCL is $373,000, which Novartis is also charging for Kymriah in that disease.
On the logistical side, Simon Ellison, director of cell and gene therapy service for World Courier – a division of AmerisourceBergen that he said handles more than 50 percent of movement for cell and gene therapies – said there should not be much of a difference between clinical trials and commercial development in terms of hurdles. He nevertheless echoed the view that the challenge now is mainly at the clinical site level.
Inclement weather is the main challenge from a logistical standpoint, he said. Indeed, if a patient lives on the East Coast, and the therapy is made on the West Coast, but there is severe weather in the Midwest, that can challenge timely delivery, Karlsberg said. People are hitting entirely new hurdles simply because CAR-T and gene therapy are such new industries, Ellison added.
Photo: Alaric DeArment, MedCity News
