Crinetics scores phase 3 win with oral treatment for acromegaly

Acromegaly is a rare condition where patients develop a benign tumor in the pituitary gland that secretes excess growth hormone, which in turn leads the liver to overproduce the hormone IGF-1.

For patients that cannot have surgery, the standard of care for acromegaly is a monthly injection of peptide analogs of somatostatin to reduce the production of growth hormone. These treatments, which consist of depots of octreotide, lanreotide or pasireotide, are injected with a large needle and can be a burdensome therapy for patients.

Crinetics’ trial, named PATHFNDR-1 enrolled patients with acromegaly to test the potential of the company’s small molecule drug paltusotine, a once-per-day oral alternative to hormone injections. The patients were originally receiving depot somatostatin analog injections and were switched to either paltusotine or a placebo during the trial.

According to the results, 83% of patients given paltusotine were able to keep their IGF-1 levels from going too high, compared to just 4% in the placebo group, meeting the trial’s primary goal. The trial also met all secondary goals, such as symptom severity and change from baseline in IGF-1 level, and paltusotine was well tolerated.

“We designed paltusotine to be the preferred therapeutic option for people living with acromegaly,” said Scott Struthers, founder and chief executive officer of Crinetics, in a public statement. “We could not be more excited by the results from PATHFNDR-1, which further reinforce our conviction that, if approved, paltusotine could address patients’ unmet need for a simple, oral, once-daily therapy.”

He added that the company expects to apply for market approval of paltusotine when it completes its second phase 3 trial in acromegaly next year. In parallel, Crinetics is testing paltusotine in a phase 2 trial in patients with carcinoid syndrome.

Another clinical-stage candidate in Crinetics’ pipeline is in phase 1/2 testing to evaluate it for the treatment of the conditions Cushing’s disease and congenital adrenal hyperplasia.

A twice-daily oral form of octreotide called Mycapssa was approved by the FDA in 2020, making it the first oral somatostatin analog for the treatment of acromegaly. Nonetheless, if paltusotine is approved, its once-per-day dosing could help the small molecule drug to stand out in the market.