February 24, 2016
By Alex Keown, BioSpace.com Breaking News Staff
LONDON – T Cell therapy is one of the more exciting explorations of personalized immuno-oncology for blood cancers being undertaken today in the pharmaceutical industry. But, there may be some serious concerns around the marketability of the treatments, an analyst with research and data firm GlobalData told BioSpace .
CAR-T therapies are seen by many as a potent weapon in the fight against cancer. Chimeric antigen receptor T cells (CAR-T) are engineered to recognize and kill cancer. Steven Rosenberg, an oncology researcher at the Center for Cancer Research, wrote in a 2013 article in “Nature Reviews Clinical Oncology” that “CAR T-cell therapy eventually may become a standard therapy for some B-cell malignancies.”
However, in a new report, Cai Xuan, GlobalData’s analyst covering Oncology and Hematology, said T Cell therapies being developed by such companies as Novartis , Juno Therapeutics , Kite Pharma and more, are being hailed as potential breakthroughs in oncology treatments for blood cancers, but the per patient cost is so high, that it must “demonstrate curative ability before it can be considered as a frontline treatment.”
Xuan pegs the cost of potential T Cell treatments as ranging between $300,000 and $500,000 per patient, while existing treatment options, which include stem cell transplantation, have a price point of between $100,000 to $200,000. In addition to the high costs of T Cell therapies, Xuan noted there are also “long and difficult manufacturing” hurdles that must be overcome as well. Xuan said the CAR-T therapies are tailor-made for the individual patient, but that means there is a “complicated and expensive” manufacturing process involved.
Already, the high price of prescription medication is under a legislative microscope here in the United States. A congressional committee held hearings earlier this month focused on companies such as Turing Pharmaceutical and Valeant that acquired older drugs and then dramatically raised their prices. Gilead ’s blockbuster Hepatitis C treatments Harvoni and Sovaldi have also been scrutinized for their high price tags for a 12-week regimen, but because those drugs are so effective in patients, they are sometimes given a pass for premium pricing. CAR-T treatments would have to be as effective in treating cancer as Sovaldi in treating hepatitis C in order not to face political pressure over its pricing, Xuan said.
Perhaps more importantly, Xuan said T Cell therapies must also address what she called a “poor safety profile.” Xuan said there have been several reports of “fatal cases of tumor lysis syndrome, cytokine release syndrome, and other organ-specific toxicities,” that have occurred during early phase trials. Additionally, she said the “aggressive nature of T-cell therapy’s side effects” means the therapy is unlikely to replace current frontline therapy options.
T Cell therapies will certainly get their “day in court” as Novartis is looking to seek approval for its CAR-T candidate (CTL019) for treatment of diffuse large B-cell lymphoma this year, making it the frontrunner among the first-generation CAR-T companies, Xuan said. Juno Therapeutics and Kite Pharma are close behind with expected filing dates in 2017, she added.
“Data suggesting impressive remission rates of up to 90 percent in treated patients are preliminary, and it is still too early to tell if these remissions will turn into cures. T-cell therapy is undoubtedly a significant step forward for immunotherapy, but whether it will reach the status of a breakthrough cure remains to be seen,” Xuan said. “In a broader sense, immuno-oncology products are being hailed as the next big wave in cancer treatment and CAR-T is definitely part of that movement; however, it is just one player among many.”
Not only does Xuan see a concern with CAR-T therapies for blood cancers, she said solid tumors present a different set of challenges. Solid tumors do not express unique tumor associated antigens, which makes it difficult to specifically target the CAR-Ts to the tumor, she said.
“To reach a solid tumor, CAR-Ts must be able to extravasate out of the blood to the tumor site, which may be deep within a tissue. Once the engineered T cells reach the tumor, they will then be faced with a host of immunosuppressive factors that are readily secreted by solid tumors to help them avoid immune detection. Not only must CAR-Ts resist becoming exhausted in this highly immunosuppressive environment, they must also be able to expand and mount an effective antitumor response,” Xuan said.
However, there are signs of some promising activity with GD2+ neuroblastoma patients, Xuan said. She said ongoing early stage clinical trials in neuroblastoma are set to “reveal more about the potential of CAR-T in these solid tumors in 2017.”
