Chiasma Initiates Second Phase III Trial of Octreotide Capsules


Chiasma, Inc. recently announced the initiation of a second Phase III clinical trial to investigate the non-inferiority of octreotide capsules to once-a-month injectable somatostatin analogs. The results are expected to support the filing of a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA).

“The initiation of this global Phase III trial marks a significant milestone for us as we continue to build our comparative efficacy, safety, and patient-reported outcome data set for Mycapssa,” said Mark Leuchtenberger, President and Chief Executive Officer of Chiasma. “We are pleased to have opened our first sites in this trial and believe this innovative oral form of octreotide has the potential to alleviate chronic injectable treatment burdens for many patients.”

The MPOWERED study is utilizing an open-label, randomized, active-controlled design comparing the efficacy, safety, and patient-reported outcomes of Mycapssa to monthly somatostatin analog injections. The primary objective of this study will be to demonstrate the non-inferiority of Mycapssa compared to injectable somatostatin analogs as measured through the time-weighted average of insulin-like growth factor-1 (IGF-1) levels during the 9-month controlled phase. After completing the randomized controlled phase, all eligible patients will have the option of entering an extension phase in which they would receive Mycapssa until product marketing or study termination.

“For the past 2 decades, most acromegaly patients have been primarily prescribed injectable somatostatin analogs for their chronic treatment requirements,” said Maria Fleseriu, MD, FACE, professor and director of NW Pituitary Center, Oregon Health & Science University, Portland, USA, the global principal trial investigator. “MPOWERED has been designed to provide unique and invaluable insights into how today’s standard of care compares with a new oral product candidate, octreotide capsules. We look forward to the learnings that will be gleaned from this international trial.”

Chiasma plans to open approximately 50 US and international sites in the MPOWERED study and to enroll 150 patients in total. Similar to Chiasma’s initial Phase III trial, all patients will receive Mycapssa during a 6-month run-in phase. Patients identified as responders to octreotide capsules after 6 months will then be randomized at a ratio of three to two to either continue on Mycapssa or revert to their previous injections, respectively, for 9 months. A non-responder sub-study will also be included in the trial to determine the efficacy of a combination of Mycapssa plus the drug cabergoline.

“Acromegaly is a challenging chronic disease that forces many patients to plan their lives around their injections, which must be administered by healthcare professionals in order to manage their disease,” said Christian J. Strasburger, MD, Chief of Clinical Endocrinology at the Department of Endocrinology, Diabetes and Nutritional Medicine, Charite Universitaetsmedizin in Berlin, Germany. “There continues to be an unmet need within the global acromegaly community for new treatment paradigms that would enable patients to manage their disease without needles.”

Acromegaly typically develops when a benign tumor of the pituitary gland produces too much growth hormone (GH), ultimately leading to significant health problems and early death if untreated. According to the US National Institutes of Health, acromegaly occurs in approximately 60 people per million in the US. In addition, researchers estimate that three to four out of every million people develop acromegaly each year. Because symptoms often develop slowly, diagnosis may be delayed by years or decades, making it difficult to determine the total number of people with the disease. Common features of acromegaly are facial changes, intense headaches, joint pain, impaired vision, and enlargement of the hands, feet, tongue, and internal organs. Serious health conditions associated with the progression of acromegaly include type 2 diabetes, hypertension, respiratory disorders, and cardiac and cerebrovascular disease.

Current treatment options include surgery to remove the pituitary tumor, radiation therapy that destroys any lingering tumor cells, and/or medical treatment in cases where these approaches are not possible or fully effective. Today’s medical treatments include dopamine agonists, GH antagonists, and injectable somatostatin analogs, which are the current standard of care.

Mycapssa is an investigational new oral drug proposed for the maintenance therapy of adult patients with acromegaly. If approved, octreotide capsules would be the first oral somatostatin analog approved for acromegaly. Chiasma submitted an NDA on June 15, 2015 for this product candidate. The FDA has accepted the NDA for filing and the PDUFA date is April 15, 2016. The PDUFA date is the target date for the FDA to complete its review of the NDA. Octreotide capsules have been granted orphan designation in the US and the European Union for the potential treatment of acromegaly. Octreotide capsules are an investigational drug that have not been approved for use in any jurisdiction. The trade name Mycapssa has been conditionally accepted by the FDA and EMA as the proprietary name for Chiasma’s octreotide capsules product candidate.

Chiasma is a late-stage biopharmaceutical company focused on improving the lives of patients suffering from orphan diseases by developing and commercializing novel oral forms of therapies that are available today only by injection. For more information, visit www.ChiasmaPharma.com.