Crinetics pads case for oral hormone disorder drug, showing regulation of key biomarker in phase 3

Crinetics Pharmaceuticals' oral med paltusotine regulated levels of a hormone associated with the pituitary gland disorder acromegaly in a phase 3 test, setting up a regulatory submission for the second half.

Paltusotine met the primary endpoint of the PATHFNDR-2 trial with 56% of the 111 participants achieving an insulin-like growth factor 1 (IGF-1) level less than or equal to 1 time the upper limit of normal compared to those on placebo, where just 5% of patients met the mark, according to a Tuesday press release.

Acromegaly is a rare hormone disorder caused by a benign tumor in the pituitary gland that secretes growth hormone, causing excess secretion of IGF-1 from the liver. This can lead to bone, joint, cardiovascular, metabolic, cerebrovascular or respiratory diseases. Symptoms include abnormal growth of hands and feet, enlargement of heart, fatigue, sleep apnea, severe swelling and other complications.

Surgical removal of the tumors is the standard initial treatment for most patients, but therapies are needed for patients without this option or when surgery is unsuccessful. This accounts for about 50% of patients, Crinetics said. Patients are traditionally offered injectable depot somatostatin analogues, but Crinetics wants to offer an easier treatment option with a daily oral med.

Paltusotine also met the key secondary endpoints of the late-stage test, including change from baseline in IGF-1 levels, change in acromegaly symptoms and regulation of growth hormone, among others.

“This study demonstrates that paltusotine can provide both symptom control as well as biochemical control in patients who are not currently on pharmacologic treatment. If approved, the prospect that paltusotine can offer an innovative, once-daily oral alternative represents a significant step forward in improving the treatment experience for patients,” said principal study investigator Monica Gadelha, M.D., Ph.D., professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro.

The therapy was well tolerated, and no serious adverse events were reported in patients who received paltusotine, Crinetics said. Treatment-emergent adverse events were comparable across the treatment and placebo arms, with the most common events reported being diarrhea, headache, joint pain and abdominal pain.

Crinetics plans to submit an approval request for paltusotine in acromegaly in the second half of the year, with a potential launch to follow in 2025.

The PATHFNDR program includes two phase 3 studies. PATHFNDR-1 previously showed that paltusotine maintained IGF-1 levels in patients who switched from monthly injectable medications, backing up earlier phase 2 studies.

This is the second time this month Crinetics has announced a clinical trial win, after the same drug met the main goal of a phase 2 trial for carcinoid syndrome. Paltusotine led to “rapid and sustained reductions in flushing episodes and bowel movement” in patients with the neuroendocrine tumor.

Crinetics’ shares were trading up 13% premarket Tuesday to $42.86 compared to $37.93 at close Monday.