Cyclerion Therapeutics had a tough day, announcing the failure of two separate clinical trials for the same drug on the same day. The company announced topline data from its Phase II proof-of-concept trial of praliciguat in diabetic nephropathy. Praliciguat is a once-daily, oral sGC stimulator. The trial did not meet statistical significance on its primary endpoint of reduction in albuminuria from baseline compared to placebo.
The company also announced topline Phase II results from its CAPACITY Phase II proof-of-concept study of praliciguat in heart failure with preserved ejection fraction (HFpEF). It did not meet statistical significance on its primary endpoint of improved exercise capacity from baseline compared to placebo.
Diabetic nephropathy is also known as diabetic kidney disease. It is a chronic loss of kidney function occurring in diabetes patients. The Phase II trial evaluated the safety and efficacy of the drug at 20 mg and 40 mg doses compared to placebo in 156 patients over a 12-week period. All the participants were 43 to 75 years of age and had type 2 diabetes and diabetic nephropathy. All were on a stable regimen of anti-glycemic drugs and renin-angiotensin-aldosterone system (RAAS) inhibitors. The primary measure of efficacy was change in urine albumin to creatinine ration (UACR). It did not meet the primary endpoint of reduction in albuminuria from baseline compared to placebo.
The company is apparently giving up on praliciguat, but plans to continue with its original plans to partner on the drug or out-license it. In light of today’s news, however, the company tried to put a positive spin on things.
“I am encouraged by the estimated reduction in albuminuria of 15% or more, compared with placebo, on top of current standard of care,” said Ian de Boer, professor, Division of Nephrology, Adjunct Professor, Epidemiology and Associate Director, Kidney Research Institute at University of Washington. “This molecule modifies pathways that are complementary to those targeted by usual care, and it warrants further investigation as a potential treatment for patients with diabetic kidney disease.”
For the other study in heart failure with preserved ejection fraction (HFpEF), the trial was evaluating the 40 mg dose compared to placebo in 196 patients with HFpEF over a 12-week period. Participants were 45 years or older and had HFpEF with an ejection fraction greater than or equal to 40%. The primary efficacy measure was change in exercise tolerance assessed by cardiopulmonary exercising testing (CPET). No statistically significant effects were observed.
Now that these Phase II trials are done, the company plans to focus on what it’s dubbing “near-term value-creating opportunities.” That includes attempts to out-license praliciguat for diabetic nephropathy, advance its STRONG SCD Phase II trial of olinciguat in sickle cell disease, its Phase I study of IW-6463 for central nervous system disorders and to decrease its monthly cash expenses by 25%.
The company reported $125 million in cash, cash equivalents and restricted cash as of September 30, which is believes is enough to continue operations through the first quarter of 2021.
The company indicated that to cut monthly expenses it will cut 30 of its 135 staffers.
Cyclerion’s stock plunged 79% at the news.
Cyclerion was spun out of Ironwood Pharmaceuticals in late-February with five orphan disease compounds. All are focused on sGC pharmacology for serious and orphan diseases.
Published: Oct 30, 2019