Crinetics Pharmaceuticals Announces Phase 2 ACROBAT Edge Study with Paltusotine in Acromegaly Met Primary Endpoint

ACROBAT Edge Results Showed Maintenance of IGF-1 Suppression with Paltusotine After Switching from Depot Somatostatin Receptor Ligand Monotherapy  

Paltusotine was observed to be well tolerated among the 60 participants in the ACROBAT Edge and Evolve Studies

On Track to Initiate Phase 3 Paltusotine Program in 1H 2021

SAN DIEGO, Oct. 26, 2020 (GLOBE NEWSWIRE) --  Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, today announced positive topline results from the company’s Phase 2 ACROBAT Edge and ACROBAT Evolve studies of paltusotine (formerly CRN00808), the company’s lead candidate for the treatment of acromegaly. The Company will hold a conference call at 8:00 a.m. Eastern Time today to discuss these results. In addition, a Key Opinion Leader (KOL) call will be held on November 20th to discuss these results in the context of the current standard of care with clinical experts.

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  (SRL) depot of either octreotide or lanreotide monotherapy  [change in IGF-1 = -0.034  (-0.107, 0.107), median (IQR)]. 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%) 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). 

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 (SAEs), and no patients required rescue treatments with standard acromegaly medications during treatment. The most common treatment-emergent adverse events (>10%) 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 M.D., 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. The potential for once daily oral paltusotine to offer similar disease control provided by first-line injected depot SRLs gives us confidence to move into a Phase 3 program to further evaluate the efficacy and safety of paltusotine.”

Scott Struthers, Ph.D., founder and Chief Executive Officer of Crinetics, added, “Overall, we believe these findings support our thesis that once daily oral paltusotine has the potential to replace injected peptide depots for acromegaly therapy. We look forward to meeting with the FDA to share these results and finalize the protocol for our planned Phase 3 program, which remains on track to begin in the first half of 2021.”

Findings from ACROBAT Edge Edge enrolled a total of 47 patients with confirmed diagnoses of acromegaly at 45 clinical sites in 13 countries. The prespecified primary analysis population (Group 1) included 25 patients who were previously treated with SRL monotherapy (octreotide or lanreotide) and had a baseline IGF-1 of >1.0x the upper limit of normal (ULN) and 1.0 ≤ 2.5252SRL + cabergoline> 1.0 ≤ 2.5103SRL + cabergoline≤ 1.054Pasireotide≤ 1.045SRL + Pegvisomant≤ 1.03

Three IGF-1 measurements were taken during a four- to six-week screening period, the average of which was defined as the “baseline” value. Following screening and four weeks after the last depot injection, each patient was treated for 13 weeks with paltusotine. All patients were started on 10 mg of paltusotine and then titrated up to 20, 30 and 40 mg at Weeks 4, 7 and 10, respectively, if the study drug was well tolerated and if the previous IGF-1 levels were >0.9x ULN at Weeks 2 and 5, and if IGF-1 levels were >1.0x ULN at Week 8. At the end of 13 weeks, 18 of the Group 1 patients who completed the dosing period were on 40 mg, two were on 30 mg, two were on 20 mg, and one was on 10 mg.

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. Furthermore, the statistically significant rise in IGF-1 levels during the four-week washout period (p0.6