As Crinetics nears FDA run for growth disease drug, a phase 2 test makes the case for carcinoid syndrome, too

As Crinetics prepares to make a tilt for FDA approval in a rare growth disorder later this year, a topline readout from a phase 2 study suggests the same drug also has the potential to treat symptoms associated with a neuroendocrine tumor.

The phase 2 study enrolled 36 patients with carcinoid syndrome who initially received either 40 mg or 80 mg daily doses of the oral somatostatin receptor type 2 (SST2) agonist, paltusotine, for eight weeks. Thirty patients completed the randomized treatment phase, with one participant from the 40 mg cohort and five from the 80 mg group discontinuing treatment.

The trial showed “rapid and sustained reductions in flushing episodes and bowel movement,” Crinetics said in a March 12 release. This included a 63% reduction from baseline in mean flushing frequency for the 24 patients with more than one bowel movement (BM) a day.

For the 16 patients experiencing more than three BMs a day—considered the upper limit of normal—there was a 60% mean reduction in mean excess frequency, the company added.

Across all the patients, there was a 61% reduction in flushing severity and a 64% reduction in BM urgency. Reductions in the frequency and severity of symptoms were observed from less than two weeks of the treatment beginning and were sustained through the eight-week regimen in both treatment naïve patients and those who had switched over from injectable somatostatin receptor ligand (SRL) therapy, which is the current mainstay treatment for carcinoid syndrome.

No treatment-related severe or serious adverse events (AEs) were reported, with diarrhea, abdominal pain, nausea and headache being the most commonly reported AEs across both dose cohorts.

Crinetics CEO Scott Struthers, Ph.D., said the latest results “confirm our decision to move expeditiously toward phase 3.”

“These results highlight the potential of paltusotine to deliver significant benefits to patients living with the debilitating symptoms of carcinoid syndrome,” Struthers added. “We plan to engage with the FDA to align on a phase 3 study design and have begun preparations to enable the initiation of a phase 3 program by the end of the year.”

Carcinoid syndrome occurs in around 20% of patients with neuroendocrine tumors, a rare, slow-growing cancer that usually originates in the digestive tract. If the cancer metastasizes to the liver it can cause carcinoid syndrome, which is typically associated with diarrhea and flushing.

While injectable SRL therapies are currently used to treat the condition, these injections are “associated with considerable treatment burden and offer inadequate relief of carcinoid syndrome symptoms for many patients,” according to Crinetics.

Paltusotine is also being developed for acromegaly, a rare hormone disorder that causes abnormal growth and swelling in adults. A phase 3 study suggested patients were able to switch over “seamlessly” to the new treatment from their usual treatment of injectable depot somatostatin drugs. The September 2023 data showed that insulin-like growth factor 1 (IGF-1) levels were maintained in 83% of patients taking the drug, compared to just 4% on placebo, which was the main goal of the study.

Results from another phase 3 trial in acromegaly are expected by the end of the month, ahead of a planned approval submission to the FDA in the growth disorder indication in the second half of the year.

To help bankroll these plans, Crinetics announced a private placement financing two weeks ago that brought in around $350 million. The biotech expects these funds to provide a cash runway through 2028.