Akari Therapeutics, a biopharmaceutical company focused on the development and commercialization of innovative therapeutics to treat orphan autoimmune and inflammatory diseases, announced that the three additional patients that were enrolled into the Phase II COBALT trial of Coversin in paroxysmal nocturnal hemoglobinuria (PNH), considered together with the earlier five patients, met the primary endpoint. The primary endpoint in this clinical trial is reduction in serum LDH (lactate dehydrogenase; an indication of hemolysis) to ≤1.8 times the ULN (upper limit of normal) for the investigator’s reference laboratory to day 28. The last three patients enrolled into the Phase II trial utilized a revised dosing regimen which included changing the initial dose of 30 mg every 24 hours to a dose of 45 mg every 24 hours. The 45 mg dosing regimen is the intended dose for the Phase III PNH trials of Coversin discussed with the U.S. Food and Drug Administration (FDA) at a Type B End of Phase II Meeting in September 2017.
The median LDH value of the last three patients enrolled, who utilised the higher 45mg dose, rapidly fell to 1.5 times the ULN at day 14 and below 1.5 times the ULN at day 28 and day 60, which was lower than the earlier patients on a 30mg dose who had a median LDH value of 2.2 times the ULN at day 28 and 1.7 times the ULN at day 60. In a total of 70 patient-months exposure, there have been no drug-related serious adverse events. In the eight patients in the COBALT Phase II trial, six were transfusion-dependent prior to the trial. Of those six patients, three have not required transfusions while on Coversin during the COBALT trial and during the Company’s long-term safety study, CONSERVE.
COBALT, the Phase II 90-day, open label single arm clinical trial is evaluating Coversin in patients with PNH who have never received a complement blocking therapy. All patients who have completed the Phase II COBALT trial entered the long-term safety study, CONSERVE. One patient in COBALT and one patient in CONSERVE with rising LDH levels were, as an alternative to higher dosing, moved as per protocol to twice daily dosing with a subsequent fall in LDH. The median LDH levels of the other three patients at Day 180 of CONSERVE was 1.77 times the ULN.
Under a separate Eculuzimab-resistent protocol, a ninth patient has been treated for 22 months with an average LDH level from month 2 onwards of 1.3 times the ULN.
“We are encouraged by the results from the Phase II trial, especially the lower mean LDH value observed in the last three patients enrolled into the trial treated with 45 mg daily compared to the patients treated with 30 mg daily,” commented Dr. David Solomon, Chief Executive Officer of Akari Therapeutics. “We are on track to progress into Phase III clinical trials in the first quarter of 2018 with the revised dosing regimen of 45 mg, as discussed with the FDA.”
“The 45 mg per day dosing of Coversin, as used for the last three patients recently enrolled into COBALT, saw plasma LDH levels in these patients fall rapidly to 1.5 times the ULN or below by Day 28,” said Principal Investigator Anita Hill, M.D., PhD, MRCP, FRCPath, Consultant Haematologist for Leeds Teaching Hospitals NHS Trust, U.K., and Lead Clinician for the National PNH Service in England. “The Phase II data suggest that Coversin is a potential alternative to existing therapy for patients with PNH, and could allow independence from intravenous infusions through self-administration.”
Akari plans to commence two Phase III PNH clinical trials with Coversin beginning with CAPSTONE in the first quarter of 2018, a Phase III trial that will include treatment naïve patients. The second Phase III trial, ASSET, is planned for the second half of 2018 and will include Soliris switch patients.
Filed Under: Drug Discovery
