60 Degrees Pharmaceuticals suspends tafenoquine trial for COVID-19

60 Degrees Pharmaceuticals announced that its subsidiary, 60P Australia, will not re-submit its investigational new drug application, or IND, for ACLR8-LR, a Phase IIB study of tafenoquine compared to placebo in patients with mild to moderate COVID-19 disease and low risk of disease progression. Tafenoquine is the active molecule in Arakoda, the company’s FDA-approved regimen for malaria prevention. The company’s board of directors decided on October 6, that recent advice from the FDA made moving forward with the ACLR8-LR clinical development plan unfeasible. The FDA has approved or authorized two marketed oral products, Lagrevio and Paxlovid, for use in cases of mild-to-moderate COVID-19 disease to reduce the rate of hospitalizations and deaths in patients with high risk of disease progression. However, the FDA has explicitly not authorized the use of those products in patients with low risk of COVID-19 disease progression. Accordingly, Lagrevio and Paxlovid are not recommended by public health agencies for that purpose. Current literature on COVID-19 shows that low risk patients have a very low risk of hospitalization. However, patients may wish to make a risk-based decision together with their physician to use a therapeutic that accelerates clinical recovery from COVID-19 symptoms if such a therapeutic were available. FDA guidance for industry implies that a regulatory pathway does exist for approval of new therapeutics that produce “sustained clinical recovery” in COVID-19 patients. FDA-approved or authorized oral therapies have either failed or have not been studied against that endpoint. 60P’s early, published Phase IIA clinical data suggested the possibility of a 2 – 2.5 day improvement in clinical recovery from cough, fever, and shortness of breath. Simulations of data from the same study suggested this might also be the case for the FDA’s preferred endpoint of “sustained clinical recovery” from all acute symptoms excluding impaired taste and smell. However, in a recent IND withdrawal acknowledgement letter from the FDA, the agency implied that a placebo-controlled study in the U.S. is permissible only if study enrollment is “restricted to a patient population in which nirmatrelvir/ritonavir or other approved or authorized therapeutics are not clinically appropriate.” The company also considered the FDA’s recommended approach of a standard of care add-on design. However, such a combination approach may not make clinical sense in a low-risk population or be Phase III enabling. In either case, the company’s board of directors determined that raising capital to support a protracted development campaign, or one requiring three additional studies, was not feasible in the current market environment. Accordingly, as outlined in its registration statement and subsequent communications to the investment community, 60P will instead continue to prepare to conduct a Phase IIA study of tafenoquine in hospitalized babesiosis patients, with the goal of requesting a pre-IND meeting with FDA before the end of 2023.