Early Indian Promise For A Cut-Price CAR-T Therapy
Executive Summary
A faculty member at the Indian Institute of Technology and the founder of Indian venture ImmunoACT hopes to deliver an indigenously developed CAR-T therapy at a fraction of current treatment costs.
India may be lagging its Asian peers in the area of cell and gene therapy but pockets of promise have emerged, with a spin-out backed by the Indian Institute of Technology (IIT), Bombay and the US National Cancer Institute hoping to deliver a cut-price CAR-T cell product.
Dr Rahul Purwar, an associate professor in the department of bioscience and bioengineering at the institute in Mumbai and founder of ImmunoACT Pvt. Ltd., underscored that India must develop its indigenous CAR-T cell platform given the promise of the therapy and the rise in the incidence of cancer in the country. Deaths from the disease were estimated at over 700,000 in 2018.
Purwar also highlighted the “geographic disparity” in CAR-T trials, where China and the US have the highest number of clinical studies underway, way ahead of other countries. The number of CAR-T trials globally has swelled from three in 2010 to about 460 in 2019, he noted.
Addressing Informa Markets’ recent Biopharma Conclave in Mumbai, Purwar noted that the CAR-T platform is no longer just limited to hematological malignancies and can have an effect on solid tumors and beyond oncology.
He referred to the recent study by researchers at Penn Medicine in the US which suggested that the CAR-T approach may be harnessed to treat heart disease. The pioneering study, published in Nature last month, found that the immunotherapy reduced cardiac fibrosis and restored heart function in mice after cardiac injury.
Penn Medicine’s Abramson Cancer Center had earlier developed what went on to became Novartis AG’s Kymriah (tisagenlecleucel), the world’s first approved CAR T-cell therapy.
Lowering The Cost Of Therapy
However, Purwar noted that CAR-T therapies at current prices are beyond the reach of most Indian patients. Kymriah and Gilead Sciences Inc.’s Yescarta (axicabtagene ciloleucel) both are reported to have US list prices of $373,000 in diffuse large B-cell lymphoma; for B-cell acute lymphoblastic leukemia, Kymriah costs $475,000. (Also see "Medicare Add-On Payments For CAR-T Should Reflect 80% Of Actual Costs, CMS Told" - Pink Sheet, 1 Jul, 2019.)
Purwar, who holds a PhD (molecular medicine) from the Hannover Medical School, Germany, and has been a research fellow at Harvard Medical School in the US, said that his firm is developing an indigenous CAR-T cell therapy which aims to lower costs by over 90% and also a CAR-T cell platform which can used for “other targets/malignancies.”
“With this in objective mind, we have collaborated with the Tata Memorial Hospital, All India Institute of Medical Sciences and the US National Cancer Institute is our ‘knowledge partner (subject matter expertise)’; ImmunoACT was started for clinical translation,” Purwar said at the meeting.
Purwar also shared some interesting cost-related aspects for CAR-T therapies, suggesting that the cost of manufacturing these could lie between $50,000-75,000 per patient. But importantly, the large chunk of these costs goes towards labor for manufacturing/quality control and then the GMP facility; the cost of goods sold is a relatively small component.
“The point I want to convey is that’s how India is nicely placed in the area to make things affordable,” Purwar said. (Also see "Gene And Cell Therapies In Asia: Indian Environment Evolving But Multiple Issues Unresolved" - Scrip, 29 Sep, 2019.)
Regulatory Approval For India Trials
Speaking to Scrip on the sidelines of the conclave, Purwar explained that his firm’s first product is a CD-19-targeting therapy for B-ALL (acute lymphoblastic leukemia), for which it has done ex vivo studies and demonstrated efficacy.
“We developed all the QC [quality control] assays and we are now continuing with animal studies and the next step is to seek approval from the Drugs Controller General of India for clinical trials,” Purwar said.
He expects to submit the paper work to the regulator by the end of this year and start clinical trials by mid-2020. "We can manufacture CD19+ CAR-T cells in enough numbers required for clinical dosage," Purwar added in his presentation at the conclave.
On whether data generated in India would be acceptable in other geographies, Purwar emphasized that his firm has followed US FDA guidelines for the clinical work. “Regarding the development process we have done everything as per international standards.”
Initial Funding
Securing funding for such cutting-edge research has, however, not always been easy in India.
Purwar said that initial funding came from the Tata Trust and some of it from the Wadhwani Research Centre for Bioengineering. IIT Bombay, the department of biotechnology and the Council of Scientific and Industrial Research are also among those who provided funding.
Purwar hasn’t approached venture capital firms as yet, but maintained that the general response of the industry has been good. “But as you know Indian industry is skeptical about taking such risks since the [ImmunoACT] CAR-T cell therapy hasn’t seen the clinic. Once we have it in the clinic and the first patient treated successfully then I think everyone will show interest.”