Crinetics Announces Positive Topline Results From Phase 2 Trial Of Paltusotine For The Treatment Of Carcinoid Syndrome; Demonstrated Rapid And Sustained Reductions In Frequency And Severity Of Flushing Episodes And Bowel Movements

Author: Benzinga Newsdesk | March 12, 2024 04:26pm

Paltusotine Treatment Demonstrated Rapid and Sustained Reductions in Frequency and Severity of Flushing Episodes and Bowel Movements

 

Paltusotine was Generally Well-Tolerated and Showed an Overall PK Profile Consistent with Prior Studies

Results Confirm Initial Positive Data Previously Reported

Management to Host a Conference Call Today at 4:30 p.m. Eastern Time

SAN DIEGO, March 12, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (NASDAQ:CRNX) a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, today announced positive topline results from its open-label Phase 2 carcinoid syndrome study of paltusotine, an oral, once-daily investigational compound being developed for the treatment of acromegaly and carcinoid syndrome.

"We are very pleased that these results from our Phase 2 study of paltusotine in carcinoid syndrome confirm our decision to move expeditiously toward Phase 3," said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. "These results highlight the potential of paltusotine to deliver significant benefits to patients living with the debilitating symptoms of carcinoid syndrome. 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."

Key Highlights from the Phase 2 Study:

The Phase 2 trial was a randomized, open-label, parallel group, multi-center study evaluating the safety, tolerability, pharmacokinetics, and efficacy of paltusotine in people living with carcinoid syndrome. A total of 36 participants were randomized to receive either 40 mg (n=18) or 80 mg (n=18) of paltusotine for 8 weeks, with the ability to dose titrate based on tolerability or inadequate control of symptoms during the first four weeks of treatment. Six participants in the 40 mg group increased their dose to 80 mg, and 3 participants in the 80 mg group increased to 120 mg. Thirty patients completed the randomized treatment phase, with 1 patient from the 40 mg group and 5 patients from the 80 mg group discontinuing treatment. Twenty-six of the 30 participants who completed the randomized treatment phase enrolled in the long-term extension phase of the study.

Results demonstrated:

• Rapid and sustained reductions in flushing episodes and bowel movement (BM)
  • 63% reduction in mean flushing frequency for patients with >1/day at baseline (n=24; p<0.0001)
  • 60% reduction in mean excess BM frequency (defined as daily bowel movements above the upper limit of normal, 3/day) in patients with >3/day at baseline (n=16; p=0.02)
  • 61% reduction in mean flushing severity (n=31; p<0.0001) and 64% reduction in mean BM urgency (n=31; p<0.0001)
  • Reductions in frequency and severity of symptoms were observed within 2 weeks of paltusotine treatment and sustained through 8 weeks in both naïve/untreated patients and those switching from prior somatostatin receptor ligand (SRL) therapy
• Overall pharmacokinetic profile of paltusotine in patients with carcinoid syndrome was consistent with expectations from healthy volunteers
• Paltusotine was generally well-tolerated with a safety profile consistent with prior clinical studies:
  • There were no treatment related severe or serious adverse events (AEs)
  • The most frequently reported AEs included diarrhea, abdominal pain, nausea and headache
  • AE findings were similar across 40 mg and 80 mg dosing groups
• Levels of biomarkers serotonin and 5HIAA provide additional evidence of paltusotine activity in carcinoid syndrome
  
   

"I am excited about the clinical improvements that paltusotine demonstrated for patients with carcinoid syndrome in this study," said Aman Chauhan, M.D., Sylvester Comprehensive Cancer Center, University of Miami and an investigator on the study. "There is a critical need for better treatment options for patients with neuroendocrine tumors who experience carcinoid syndrome. The results from this study of paltusotine are highly encouraging and I look forward to the next stage in its development."

Data Review Conference Call

Crinetics will hold a conference call and live webcast today, Tuesday, March 12 at 4:30 p.m. Eastern Time to discuss the results from the Phase 2 study. To participate, please dial 1-888-886-7786 (domestic), 1-416-764-8658 (international), or request a callback here and refer to conference ID 02300008. To access the webcast, click here. Following the live event, a replay will be available on the Investors section of the Company's website. 

About the Phase 2 Study

The Phase 2 study is a randomized, open-label, parallel group, multi-center study evaluating the safety, tolerability, pharmacokinetics and efficacy of paltusotine in people living with carcinoid syndrome. This study consists of a randomized treatment phase followed by a long-term extension phase. A total of 36 patients with documented carcinoid syndrome requiring medical therapy were randomized to receive either 40 mg or 80 mg of daily oral paltusotine for 8 weeks. For additional information, please visit clinicaltrials.gov (NCT05361668).

About Carcinoid Syndrome

Carcinoid syndrome is found in approximately 20% of patients with neuroendocrine tumors (NETs). NETs are a rare, slow-growing type of cancer that arise most often in the digestive tract. When these tumors metastasize to the liver, carcinoid syndrome can occur and is most commonly characterized by diarrhea and flushing. While injectable depot somatostatin receptor ligand (SRL) therapies are mainstay treatments for carcinoid syndrome, these injections are associated with considerable treatment burden and offer inadequate relief of carcinoid syndrome symptoms for many patients.

About Paltusotine

Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist and is currently in investigational Phase 3 studies for acromegaly and a Phase 2 study for carcinoid syndrome. It was designed by the Crinetics' discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In Phase 2 studies and the recently completed PATHFNDR-1 Phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome further support paltusotine's potential use beyond acromegaly.

Posted In: CRNX