Kalytera Therapeutics is ramping up its cannabidiol program, with ambitions to bring a treatment for graft-versus-host disease into phase 3 by the end of the year. The drug is in phase 2 studies for both the treatment and prevention of GVHD, a life-threatening condition that has no approved therapies.
GVHD is a serious complication of bone marrow transplant, occurring when the transplanted donor cells mount an immune response against the recipient’s healthy tissues and organs. Steroids may be used to try and limit the immune reaction, but this does not work in all patients. Kalytera estimated that about 50% patients who receive a bone marrow transplant from a fully matched sibling donor and up to 70% of patients who receive bone marrow from an unrelated donor will develop "some level" of GVHD.
Cannabidiol (CBD) is a nonpsychotropic ingredient of cannabis—it acts on many of the same receptors as tetrahydrocannabinol (THC), the part of cannabis that causes users to get "high." Cannabis remains classed as a Schedule I drug—meaning it has "no currently accepted medical use and a high potential for abuse"—but the FDA is set to make a decision next week on GW Pharma's CBD treatment for rare epilepsies. An approval would pave the way for other companies, like Kalytera, that are working on cannabis-based treatments.
Kalytera's CBD candidate has completed two phase 2a studies in the prevention of GVHD. One of the studies involved 48 patients who received 150 mg of CBD twice daily for the week leading up to bone marrow transplant, and for 30 days after.
No patients developed acute GVHD while on CBD. The rate of acute GVHD by day 100 was 12%, a fraction of the 46% seen in historical control subjects who received standard GVHD prophylaxis at the same institution in Israel, the company said. Kalytera expects to complete its phase 2b study in the prevention of GVHD by early 2019.
"With no FDA approved therapy for the prevention of acute GVHD, there exists an important unmet medical need that we believe we can address. Based on the positive and encouraging results from the two prior Phase 2a clinical studies that we completed in prevention of GVHD, we are optimistic that our CBD product will address this unmet need, and will be demonstrated to be a safe and effective means to prevent the onset of acute GVHD," said Kalytera CEO Robert Farrell.
As for the treatment of GVHD, the company is planning a "seamless Phase 2-3 pivotal registration study" later this year. It will enroll about 135 patients and assess safety and efficacy of multiple doses of CBD in treating acute GVHD.
A single-arm, open-label phase 2a study in 10 patients whose disease did not respond to steroids was "positive and highly encouraging," the company said. Nine of the patients responded to CBD, with seven achieving complete remissions.
"As we advance our GVHD program into the final phases of clinical testing, we will begin seeking regional partnering opportunities outside of North America to provide non-dilutive sources of funding and monetize this program through licensing, milestone and royalty revenue," Farrell said in a letter to shareholders in April.