Fate Therapeutics has seen improvements in 4 patients with treatment-resistant systemic sclerosis who were dosed with its off-the-shelf CAR-T cell therapy in as little as 3 months.
Data presented (PDF) today at the International Society for Stem Cell Research (ISSCR) in Montreal come from an ongoing phase 1 basket trial encompassing other autoimmune diseases such as lupus. So far, investigators have treated a total of 30 patients.
“We were not expecting to see clinical responses so early,” Vaneet Sandhu, M.D., rheumatologist and vice president of clinical development at Fate Therapeutics, told Fierce. “Certainly, it's still early but so far, having treated these patients before, this is really exciting.”
The patients received little to no immunodepleting before dosing with Fate’s anti-CD19 CAR-T cells (FT819), a unique aspect of the trial compared to others where patients can receive intense immunodepleting, Sandhu explained.
Each of the 4 patients who were treated with FT819 showed improvement in the modified Rodnan skin score, indicating their skin became thinner and more flexible.
All the patients tolerated the treatment, with no cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft versus host disease (GvHD), according to the biotech. Three of the patients were dosed with the CAR-T cells as outpatients or discharged in less than 24 hours.
Systemic sclerosis is a rare autoimmune disease that affects around 670,000 people globally. The disease targets multiple organs of the body and can cause thickening of the skin, Raynaud’s phenomenon, interstitial lung disease, and kidney and GI issues.
Patients with systemic sclerosis might receive other drugs on the market that target complications of this disease. Boehringer Ingelheim’s Ofev and Genentech’s Actemra are used to improve the interstitial lung disease associated with systemic sclerosis. But there are no FDA-approved treatments that target this multi-organ disease as a whole.
San Diego-based Fate specializes in programmable off-the-shelf CAR-T cell therapies. Compared to autologous CAR-T cells, Fate’s cell bank of induced pluripotent stem cells (IPSC) allows for programmable, on demand, reproducible, and scalable CAR-T cells, according to the company.
The FT819 candidate is designed to eliminate pathological auto-reactive B cells, which are responsible for causing swelling and thickening of the skin. The prospect also has a knockout of the T-cell receptor alpha constant (TRAC) locus, which eliminates the possibility of GvHD.
“It's allowing us to keep saying this product was designed to balance safety and efficacy,” Sandhu told Fierce.
The trial expanded to include patients with systemic sclerosis after researchers saw promising data from the treatment of Lupus patients with FT819. The data from these 3 patients, presented during the American Society of Gene and Cell Therapy (ASGCT) meeting in May, showed a clinical improvement in disease activity without worsening in other clinical measures and no CRS, ICANS, or GvHD. Additionally, 2 of the 3 patients reached a lupus low-disease activity state (LLDAS).