A voluntary pause for BioCryst Pharmaceuticals’ complement-mediated disease therapy has been upgraded to a partial FDA clinical hold, but the biotech now believes it has an idea of what’s behind the safety signals that have ground the program to a halt.
The new revelations, included in the company’s first-quarter earnings report Thursday, provided the most clarity to date on what spurred the early April decision to pause trials testing BCX9930 in patients with paroxysmal nocturnal hemoglobinuria (PNH). The rare disease is marked by the destruction of red blood cells and poor bone marrow function.
BioCryst reported in early April that the trials were being paused as the company investigates elevated serum creatinine levels, which is a sign of impaired kidney function.
A preliminary investigation by the company has now found that the 500 mg dose level, particularly without escalation, is likely to blame. BioCryst also disclosed that “subsequent” to its voluntary pause, the FDA slapped on a partial clinical hold. A spokesperson for the company said the partial hold was placed “later in April,” sometime after an April 11 follow-up disclosure.
BCX9930 is being tested in two mid-phase trials called Redeem in patients with PNH as well as a third phase 2 study called Renew for patients with kidney diseases.
The effort to lower the dose comes after three patients in the PNH studies who received treatment reported early onset and moderate to severely elevated serum creatinine. BioCryst estimates that a third of patients treated in the two PNH trials have had “early increases in serum creatinine.”
Separately, “slowly evolving” increases in creatinine levels were identified in roughly 40% of patients who switched to the 500 mg dose in the open-label extension of the proof-of-concept Renew study.
BioCryst now believes that lowering the dose to 400 mg will do the trick and the company has pledged to work with regulators to amend the trial design.
“As we complete our investigation, we will continue to be comprehensive and deliberate, with a primary focus on patient safety,” said Chief Medical officer William Sheridan. “After consultation with regulators, we will determine the next step for the BCX9930 program.”
Under the conditions of the hold, the company is unable to enroll new patients but patients who have already been treated can continue if they have no other treatment option.
Cost could also be at play as the company considers its next steps. BioCryst reported that R&D expenses jumped more than 50% to $65.4 million for the quarter “primarily due to increased investment in the development of our Factor D program, including BCX9930.”
The company currently has nearly $450 million in cash and investments but expects operating expenses in 2022 to be as much as $480 million. That places a lot of trust on revenue accrued from Orladeyo, the company’s approved med to treat hereditary angioedema. The company expects full-year revenue of the drug to be “no less” than $250 million.