RARE Daily

Crinetics Pharmaceuticals Reports Positive Phase 2 Results of Acromegaly Therapy

October 26, 2020

Rare Daily Staff

Crinetics Pharmaceuticals reported positive topline results from the company’s phase 2 ACROBAT Edge and ACROBAT Evolve studies of paltusotine, the company’s lead experimental candidate for the treatment of the rare growth disorder acromegaly.

Acromegaly is generally caused by a benign growth hormone secreting tumor in the pituitary. Excess growth hormone secretion causes excess secretion of IGF-1 from the liver, which causes bone and cartilage overgrowth, organ enlargement, and changes in glucose and lipid metabolism. The symptoms of acromegaly include abnormal growth of hands and feet and changes in shape of the bone and cartilage that result in alteration of facial features. Overgrowth of bone and cartilage and thickening of tissue leads to arthritis, carpal tunnel syndrome, joint aches, enlarged lips, nose and tongue, deepening of voice due to enlarged vocal cords, sleep apnea due to obstruction of airways and enlargement of heart, liver and other organs.

Paltusotine is an orally available nonpeptide biased agonist that is designed to be highly selective for the somatostatin receptor subtype 2. It was designed to provide a once daily option for patients with acromegaly and neuroendocrine tumors that are currently treated by injected therapies that have sales of approximately $3.1 billion annually.

The prespecified primary endpoint in Edge was achieved, showing that once daily oral paltusotine maintained insulin-like growth factor-1 (IGF-1) levels at week 13 in acromegaly patients who were switched from an injected somatostatin receptor ligand depot of either octreotide or lanreotide monotherapy.

There were 25 patients enrolled in this prespecified primary analysis population (Group 1). During the four-week washout period after the 13-week treatment period, Group 1 patients showed a meaningful (>20 percent) and prompt (within two weeks) rise in IGF-1 levels from baseline, which characterized the magnitude of therapeutic activity of oral paltusotine in acromegaly patients. Edge also enrolled an additional 22 patients into four different exploratory populations (Groups 2-5).

The primary endpoint in the primary analysis population prespecified in the Statistical Analysis Plan (Group 1) showed that at the end of the 13-week treatment period, the median IGF-1 was 1.343, compared to the median IGF-1 of 1.335 at baseline (p>0.6 for change from baseline), indicating there was no statistically significant difference in IGF-1 control after patients had switched from pre-trial injected therapy to oral paltusotine monotherapy.   

Paltusotine was generally well tolerated among the 60 ACROBAT participants (including both Edge and Evolve), which is consistent with prior clinical findings in healthy volunteers. There were no discontinuations due to drug-related adverse events, no safety signals seen in clinical laboratory analyses, no treatment-related serious adverse events, and no patients required rescue treatments with standard acromegaly medications during treatment. The most common treatment-emergent adverse events (>10 percent) included: headache, arthralgia, fatigue, peripheral swelling, paresthesia and hyperhidrosis.

“These results from Edge and Evolve support the potential to effectively switch acromegaly patients from their current depot injections to a once-daily oral treatment while maintaining hormonal control,” stated Alan Krasner, chief medical officer of Crinetics. “The heterogeneous nature of the ACROBAT patient population is representative of the real-world population, where acromegaly patients are prescribed a variety of treatments in an effort to control their IGF-1 levels, often unsuccessfully.”

Photo: Alan Krasner, chief medical officer of Crinetics

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