Kalytera’s cannabidiol (CBD) compound efficiently prevents graft-versus-host disease (GVHD) in patients receiving bone marrow transplants from matched unrelated donors, interim data from a Phase 2 study show.
Considering the study’s positive results so far, the company announced that it will halt the Phase 2 study and proceed directly to initiate a Phase 3 clinical trial.
Bone marrow transplant is one of the most effective curative treatments for patients with blood cancers, such as multiple myeloma. However, it comes with great risk of acute GVHD, a life-threatening condition that happens when the transplanted donor immune cells see the recipient’s body as foreign and react against it.
Acute GVHD usually occurs within the first 100 days post-transplant and causes skin rash, liver problems, and intestinal symptoms such as nausea and diarrhea.
It is estimated that up to 50% of patients receiving bone marrow transplants from a sibling donor, and 60%–70% of patients receiving the transplant from a matched unrelated donor, will develop grade 2–4 GVHD. Acute GVHD grades go from 0 to 4 according to number and extent of organ involvement.
There are no approved therapies for the prevention of acute GVHD; current therapeutic strategies commonly rely on the suppression of the immune system, which can lead to severe infections.
Thus, the development of efficient therapies to prevent acute GVHD is a major goal of modern bone marrow transplantation medicine.
Kalytera’s new, proprietary CBD product is an oral formulation in olive oil designed to overcome CBD’s issues of poor oral bioavailability and stability. CBD is a non-psychoactive component of cannabis with immunosuppressive properties.
The company’s open-label, multi-center, Phase 2 study (NCT03840512) was designed to evaluate the efficiency and safety of three oral doses of CBD (75, 150, or 300 mg twice a day) in the prevention of acute GVHD in patients receiving bone marrow transplants from matched unrelated donors.
So far, 24 patients were enrolled and received either the low dose (12 patients) or the medium dose (12 patients) of CBD for 105 days following bone marrow transplant. Participants were followed for an additional 80 days after treatment cessation.
The interim results showed that only one patient receiving the low dose of CBD (8%) and no patients in the medium dose group developed grade 2–4 acute GVHD. The GVHD developed by the patient in the low-dose group was grade 2, a non-serious form of the disease.
The pronounced reduction in the frequency of acute GVHD from a historic norm of 60%–70% to less than 10% in patients receiving bone marrow transplants from matched unrelated donors suggests that Kalytera’s CBD is a strong therapeutic candidate for this disease.
“We did not expect the results from the low-dose cohort [group] to be as positive as they were, and now we have interim results from the medium-dose cohort that are equally as good,” Robert Farrell, Kalytera’s president and CEO, said in a press release.
The results were consistent with data from two previous clinical studies involving 60 patients receiving bone marrow transplants from matched unrelated donors. In those studies, a total of two patients developed grade 2–4 GVHD while receiving CBD.
Farrell stated that the company believes these data “exceed what will be required in a Phase 3 registration study to demonstrate the efficacy of CBD in prevention of acute GVHD, and leave little or no room for improvement with the high dose,” and that it has “decided to halt the ongoing Phase 2 clinical study without enrolling the high-dose cohort, and proceed directly to initiate a Phase 3 clinical registration study.”
The multinational, double-blind, placebo-controlled Phase 3 study is expected to enroll 50 patients, who will be randomly selected to receive either a 150-mg dose of CBD or a placebo twice daily for approximately 100 days. The study will last approximately 12 months.
Enrollment will start at the same clinical sites in Israel and Australia where the Phase 2 trial is being conducted, then will be expanded to one or two additional sites in both the United States and Europe.
Kalytera believes the results of the Phase 3 study will meet the requirements for CBD approval by regulatory agencies around the world, potentially making its CBD product the first approved therapy for prevention of acute GVHD following bone marrow transplantation.
The company plans to present the results of the Phase 2 study, along with findings on the mechanism of action of CBD in the prevention and treatment of acute GVHD, at upcoming scientific meetings and to submit those data for publication.