Chiasma Announces First Patient Is Randomized in Phase 3 CHIASMA OPTIMAL Clinical Trial of Octreotide Capsules in Patients with Acromegaly

Phase 3 MPOWERED Trial Surpasses 50% Patients Randomized


WALTHAM, Mass., Sept. 27, 2017 (GLOBE NEWSWIRE) -- Chiasma, Inc. (Nasdaq:CHMA), a clinical-stage biopharmaceutical company focused on improving the lives of patients with rare and serious chronic diseases, today provided an update on both of its international Phase 3 clinical trials of its octreotide capsules product candidate, conditionally trade-named Mycapssa®, for the maintenance therapy of adult patients with acromegaly.  

The company announced the randomization of the first patient in its new Phase 3 trial referred to as “CHIASMA OPTIMAL” (Octreotide capsules vs. Placebo Treatment In MultinationAL centers), meeting its previous guidance that enrollment in the study would begin during the second half of 2017.

The CHIASMA OPTIMAL study is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA)’s Division of Metabolism and Endocrinology Products. A SPA is a process by which an applicant and the FDA reach an agreement on the protocol design, endpoints and analysis of a Phase 3 clinical study prior to initiation, in order to determine if the study adequately addresses scientific and regulatory requirements for FDA approval.

Chiasma also announced it has recently surpassed 50% patients randomized in its international Phase 3 clinical trial, referred to as MPOWERED (Maintenance of Acromegaly Patients with Octreotide Capsules Compared With Injections – Evaluation of REsponse Durability). It is a global, randomized, open-label and active-controlled, 15-month trial.

“This is an important day for Chiasma, as we achieved two significant milestones toward advancing octreotide capsules as a maintenance treatment for adult acromegaly patients,” said Mark Fitzpatrick, president and CEO of Chiasma. “Beginning enrollment in our CHIASMA OPTIMAL Phase 3 study is an important step toward our goal of resubmitting a New Drug Application with the FDA. We also are encouraged by our progress in enrolling patients in MPOWERED, Chiasma’s international Phase 3 study of octreotide capsules, to potentially support regulatory approval in Europe. We strongly believe in Mycapssa as a potential new treatment option for adult patients with acromegaly, and we look forward to continuing this important mission.”

Octreotide capsules are an investigational new oral drug proposed for the maintenance therapy of adult patients with acromegaly. Acromegaly is most commonly caused by a benign tumor of the pituitary gland that produces excess growth hormone (GH), ultimately leading to significant health problems and early death if untreated. GH regulates multiple metabolic processes and stimulates the production of insulin-like growth factor 1 (IGF-1) in the liver, which stimulates the growth of bones and other tissues. If approved, octreotide capsules may be the first oral somatostatin analog treatment option available for acromegaly patients, where the current standard of care is somatostatin analog injections.

About the CHIASMA OPTIMAL Phase 3 Trial
OPTIMAL is a randomized, double-blind, placebo-controlled, nine-month clinical trial in 50 adult acromegaly patients (at least 20% of whom must be recruited from the United States) whose disease is biochemically controlled, based upon levels of IGF-1, a byproduct of increased GH levels caused by acromegaly, on injectable somatostatin analogs at baseline (average IGF-1 ≤1.0 x upper limit of normal (ULN)). The patients must also have confirmed active acromegaly following their last surgical intervention based upon an elevated IGF-1 at that time of ≥1.3×ULN. The trial will be randomized on a 1:1 basis to octreotide capsules or placebo. Patients will be dose titrated from 40mg per day to up to a maximum of 80mg per day, equaling two capsules in the morning and two capsules in the evening. Patients meeting predefined withdrawal criteria during the course of the trial will revert to their original treatment of injections and will be monitored for the remainder of the trial.

The primary endpoint of the study is the proportion of patients who maintain their biochemical response compared to placebo at the end of the nine-month, double-blind, placebo-controlled period as measured using the average of the last two IGF-1 levels ≤ 1.0×ULN. Hierarchical secondary endpoints that will be considered by the FDA in evaluating the totality of evidence for octreotide capsules treatment effect include: proportion of patients who maintain GH response at week 36, compared to screening; time to loss of response of IGF-1 > 1.0×ULN; time to loss of response of IGF-1 > 1.3×ULN; change in mean GH from screening to end of treatment; and change in IGF-1 from baseline to end of treatment. Chiasma anticipates the release of top-line data from this Phase 3 clinical trial by the end of 2019.

About the MPOWERED Phase 3 Trial
Chiasma is conducting an international Phase 3 clinical trial under a protocol accepted by the European Medicines Agency (EMA) for the company’s octreotide capsules product candidate for the maintenance therapy of adult patients with acromegaly. The trial, referred to as MPOWERED (Maintenance of Acromegaly Patients with Octreotide Capsules Compared With Injections – Evaluation of REsponse Durability), is a global, randomized, open-label and active-controlled, 15-month trial. It is expected to enroll up to 150 adult acromegaly patients, of which it expects to randomize at least 80 patients who are responders to octreotide capsules following a six-month run-in to either octreotide capsules or injectable somatostatin receptor ligands (octreotide or lanreotide), and then followed for an additional nine months. The trial was initiated in March 2016 and is designed to evaluate the proportion of patients who maintain their biochemical response to octreotide capsules and patient-reported outcomes in patients treated with octreotide capsules, compared to patients treated with standard of care injectable somatostatin receptor ligands. The company anticipates the release of top-line data from this Phase 3 clinical trial in 2020.

About Chiasma
Chiasma is focused on improving the lives of patients who face challenges associated with their existing treatments for rare and serious chronic diseases. Employing its Transient Permeability Enhancer (TPE®) technology platform, Chiasma seeks to develop oral medications that are currently available only as injections. The company has reached agreement with the FDA on the design of a new Phase 3 clinical trial for its octreotide capsules product candidate, conditionally trade-named Mycapssa®, for the maintenance therapy of adult patients with acromegaly. Chiasma is headquartered in the United States with a wholly owned subsidiary in Israel. Mycapssa and TPE are registered trademarks of Chiasma. 

Forward-Looking Statements
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the company’s commitment to develop new treatment options for patients with rare and serious chronic diseases, specifically acromegaly, the company’s efforts to potentially obtain regulatory approval in the United States by conducting the new Phase 3 OPTIMAL clinical trial under a Special Protocol Assessment, the company’s efforts to potentially obtain regulatory approval in Europe by conducting the ongoing MPOWERED Phase 3 clinical trial, the timing of receipt of top-line data and submission of regulatory filings, including the company’s ability to obtain top-line data from the OPTIMAL trial by the end of 2019 and the company’s ability to obtain top-line data from the MPOWERED trial in 2020. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the regulatory review and approval process generally; risks associated with Chiasma’s Phase 3 clinical trial to support regulatory approval of octreotide capsules in the E.U.; risks associated with Chiasma conducting an additional randomized, double-blind and controlled Phase 3 clinical trial to support regulatory approval of octreotide capsules in the United States, including risks related to the enrollment, timing and associated expenses; risks associated with Special Protocol Assessment agreements, including the risk that Special Protocol Assessment agreements are not a guarantee of approval and the FDA may not approve octreotide capsules even if the Phase 3 trial is successful; risks associated with the ability of the company’s suppliers to pass future regulatory inspections; risks associated with obtaining, maintaining and protecting intellectual property; risks associated with Chiasma’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; the risk that octreotide capsules, if approved, will not be successfully commercialized; the risk of competition from currently approved therapies and from other companies developing products for similar uses; risks associated with Chiasma’s financial position, including its ability to manage operating expenses and/or obtain additional funding to support its business activities; risks associated with Chiasma’s dependence on third parties; and risks associated with defending any litigation, including the risk that we incur more costs than we expect and uncertainty involving the outcome. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Chiasma’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2017 filed with the Securities and Exchange Commission (SEC) on August 10, 2017, and in subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Chiasma undertakes no duty to update this information unless required by law.

Contact:
Andrew Blazier
Sharon Merrill Associates
(617) 542-5300
chma@investorrelations.com