Crinetics Reports Positive Interim Results of Experimental Oral Therapeutic for Acromegaly

Rare Daily Staff

Crinetics Pharmaceuticals reported positive interim results from its ongoing mid-stage study of its once daily oral therapy for acromegaly.

The data from ACROBAT Edge phase 2 trial showed that acromegaly patients switching from injectable depot therapy to once daily oral paltusotine maintained IGF-1 levels previously achieved with commercially available depot injections of somatostatin receptor ligands.

Acromegaly is a hormonal disorder that results from the pituitary gland producing too much growth hormone (GH). It is most often diagnosed in middle-aged adults, although symptoms can appear at any age. Signs and symptoms include abnormal growth and swelling of the hands and feet; bone changes that alter various facial features; arthritis; carpal tunnel syndrome; enlargement of body organs; and various other symptoms.

The condition is usually caused by benign tumors on the pituitary called adenomas. Rarely, it is caused by tumors of the pancreas, lungs, and other parts of the brain. Acromegaly is usually treatable but when left untreated, it can result in serious illness and premature death. When GH-producing tumors occur in childhood, the disease that results is called gigantism rather than acromegaly.

When surgery is unsuccessful in reducing tumors, drugs can be used. About 50 percent of acromegaly patients are candidates for treatment with drugs, usually long-acting somatostatin receptor ligands that require monthly injections.

Paltusotine is an orally available nonpeptide biased agonist that is designed to be highly selective for the somatostatin sst2 receptor. It was designed by Crinetics to provide a once daily option for patients with acromegaly and neuroendocrine tumors that are currently treated by injected therapies.

“The currently available intramuscular or deep-subcutaneous depot drugs are painful, and leave many of us with a return of acromegaly symptoms at the end of each monthly injection cycle,” said Jill Sisco, president of the Acromegaly Community, the largest global advocacy and support organization for acromegaly patients. “Travel to physician’s offices or hospitals for these injections disrupts our daily lives. The potential opportunity to switch to a once daily oral therapy that could work as well as the currently available injections to lower our IGF-1 levels is very exciting.”

Interim results from an exploratory analysis of the first 13 patients who entered the Edge trial on octreotide or lanreotide depot monotherapy showed that, as of the cutoff date, switching to once daily oral paltusotine maintained patient IGF-1 levels at those achieved with prior depot therapy. Ten of the 11 patients in the first group who completed paltusotine treatment maintained IGF-1 levels within 15 percent of their respective baseline levels at week 13. No patient required “rescue therapy” with prior injected peptide acromegaly therapy after switching to paltusotine. Paltusotine was well tolerated and there were no discontinuations due to drug-related adverse events. Topline data from the trial is anticipated in the fourth quarter of 2020.

“With these data we are proceeding with plans to begin the Phase 3 stage of our development program for acromegaly in the first half of 2021 when full results from the Phase 2 trials are expected to be available,” said Scott Struthers, founder and CEO of Crinetics. “These results also give us confidence to expand the clinical program for paltusotine to include patients with neuroendocrine tumors who suffer from carcinoid syndrome, and we are evaluating how to best integrate this indication into our overall development plans.”

Photo: Scott Struthers, founder and CEO of Crinetics