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28 patients have completed the open-label Edge trial measuring IGF-1 levels after 13 weeks of treatment when patients with acromegaly were switched to once daily oral paltusotine from commercially available depot injections of the peptide somatostatin receptor ligands (SRLs)
Recruitment for the Edge and Evolve trials has been completed with 47 and 13 patients, respectively, and topline data is planned for the fourth quarter of 2020
Management expects to use the results for the two trials to support the initiation of Phase 3 clinical development for paltusotine in the first half of 2021
SAN DIEGO, June 11, 2020 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (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 that over 50% of the patients enrolled in the ACROBAT Edge Phase 2 clinical trial have completed the study. So far, 28 of the 47 patients enrolled have completed the study, which is investigating the effects of once daily oral paltusotine on IGF-1 levels after switching patients from injectable depot therapy.
“The completion of the trial by these 28 patients is a major milestone for our clinical program at Crinetics. We are extremely grateful for the dedication of our patients and staff at clinical trial sites for keeping us on track in the face of the COVID-19 pandemic,” said Alan Krasner, M.D., Chief Medical Officer of Crinetics.
“As we previously stated, we expect to announce topline results in the fourth quarter of this year. These data together with interactions with the regulatory agencies will guide finalization of our Phase 3 clinical plan which is anticipated to begin in the first half of 2021,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics.
Based on the results of the previously announced interim analysis, Crinetics believes that the data from Edge is supportive of moving forward into Phase 3. Enrollment in the ACROBAT Evolve study was discontinued at the same time that enrollment in Edge was completed. Patients already enrolled in Evolve have continued in the study. Topline data from the 47 patients in Edge, 25 of which entered the trial on octreotide LAR or lanreotide depot monotherapy (group 1), and the 13 patients in Evolve is expected in the fourth quarter of 2020. To date, the company has not experienced significant disruptions in completing the Edge and Evolve studies due to the COVID-19 global pandemic.
Trial Design for ACROBAT Edge
ACROBAT Edge (NCT03789656) is an ongoing open label, single-arm exploratory study designed to evaluate the safety and efficacy of paltusotine in patients with acromegaly who have not achieved normal IGF-1 levels despite stable octreotide LAR or lanreotide depot therapy alone (group 1) or combined with a dopamine agonist (group 2). Additional exploratory subgroups were also eligible for enrollment in this trial, all of whom have normal IGF-1 at baseline: patients treated with octreotide or lanreotide in combination with a dopamine agonist (group 3), pasireotide LAR monotherapy (group 4), or octreotide or lanreotide in combination with pegvisomant (group 5). Eligible patients receive their last injection of their previous SRL 4 weeks prior to switching to once daily oral paltusotine monotherapy for a 13-week dose titration period, followed by a 4-week drug washout period. The primary endpoint is change in IGF-1 from baseline to the completion of the 13-week dose titration period.
Paltusotine (formerly CRN00808) is an orally available nonpeptide biased agonist that is designed to be highly selective for the somatostatin sst2 receptor. It was designed by the Crinetics discovery team to provide a once daily option for patients with acromegaly and neuroendocrine tumors that are currently treated by injected therapies that sell approximately $3.1 billion annually. Non-clinical chronic toxicology studies are complete and no dose limiting toxicity was identified at the maximum feasible doses in rats and dogs. Crinetics previously completed a Phase 1 trial that showed potent suppression of the GH axis in healthy volunteers, which provided clinical proof-of-concept. In addition, the molecule’s observed plasma half-life of approximately 2 days suggested the potential for paltusotine for once daily oral administration. A subsequent Phase 1 trial showed that paltusotine was 70% orally bioavailable.
Acromegaly is a serious disease generally caused by a benign growth hormone (GH) secreting tumor in the pituitary. Excess GH secretion causes excess secretion of insulin-like growth factor-1 (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, deepening of voice due to enlarged vocal cords, sleep apnea due to obstruction of airways, and enlargement of lips, nose, tongue, heart, liver, and other organs.
Surgical removal of pituitary adenomas, if possible, is the preferred initial treatment for most acromegaly patients. Pharmacological treatments are used for patients that are not candidates for surgery, or when surgery is unsuccessful in achieving treatment goals. Approximately 50% of patients with acromegaly prove to be candidates for pharmacological treatment. Long-acting SRLs are usually the initial pharmacologic treatment, however these drugs require monthly injections and are commonly associated with pain, injection site reactions, and increased burden in the lives of patients. Although over 90% of patients have demonstrable responses to SRLs (Annals of Internal Medicine. 1992; 117:711-718) only 20-40% of patients achieve normalization of IGF-1 (J Clin Endocrinol Metab 99: 791–799, 2014). Additional pharmacological treatment options include dopamine agonists or GH receptor antagonists that may be used in combination with SRLs.
About Crinetics Pharmaceuticals
Crinetics Pharmaceuticals is a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors. The company’s lead product candidate, paltusotine (formerly CRN00808), is an oral, selective nonpeptide somatostatin receptor type 2 biased agonist undergoing two Phase 2 clinical trials for the treatment of acromegaly, an orphan disease affecting more than 25,000 people in the United States. Crinetics plans to advance paltusotine into a Phase 3 trial in acromegaly and a Phase 2 trial for the treatment of carcinoid syndrome associated with neuroendocrine tumors in 2021. The company is also developing an oral nonpeptide somatostatin type 5 agonist for hyperinsulinism, as well as an oral nonpeptide ACTH antagonist for the treatment of Cushing’s disease, congenital adrenal hyperplasia and other diseases of excess ACTH. All of the company’s drug candidates are new chemical entities resulting from in-house drug discovery efforts and are wholly owned by the company. For more information, please visit www.crinetics.com.
Crinetics cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the potential for any of our ongoing clinical trials to show safety or efficacy; the potential benefits of paltusotine for acromegaly patients; the potential to initiate a pivotal Phase 3 trial of paltusotine in acromegaly based on interim results obtained to date and the timing thereof; the planned expansion of the paltusotine development program to include the treatment of carcinoid syndrome in patients with neuroendocrine tumors and the expected timing thereof, including initiation of a Phase 2 trial in these patients; and the anticipated timing of topline data for Edge and Evolve. The inclusion of forward-looking statements should not be regarded as a representation by Crinetics that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Crinetics’ business, including, without limitation: potential delays in the commencement, enrollment and completion of clinical trials; advancement of paltusotine into a Phase 3 trial is dependent on and subject to the receipt of further feedback from the FDA; the COVID-19 pandemic may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics’ clinical trials and nonclinical studies for paltusotine and its other development candidates; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; Crinetics may use its available capital resources sooner than it expects; Crinetics’ ability to obtain and maintain intellectual property protection for its product candidates; and other risks described under the heading “Risk Factors” in documents the company files from time to time with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Crinetics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Chief Financial Officer
Robert H. Uhl