February 10, 2015

Chiasma Inc. Release: Newly Published Phase 3 Study Results

Show Positive Outcomes For Octreotide Capsules In People With Acromegaly, A Serious Hormonal Disorder

NEW YORK and JERUSALEM, Feb. 9, 2015 /PRNewswire-USNewswire/ — Chiasma Inc., a U.S. privately-held biopharma company, announced today that results from a multicenter Phase III study of the investigational new drug, octreotide capsules, were published online for early release on Feb. 9, ahead of print, by the Journal of Clinical Endocrinology & Metabolism (JCEM).

The investigational drug, octreotide capsules, is an oral form of the peptide octreotide, a somatostatin analog, for potential use in the treatment of adults with acromegaly, a rare endocrine disease. Patients were evaluated for biochemical and symptomatic disease control over a 13-month period following treatment with octreotide capsules. Sixty-five percent of patients who received octreotide capsules twice-a-day achieved disease control, as measured by circulating concentrations of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) concentrations, at 7 months (core treatment period), meeting the primary endpoint and 62% achieved disease control at 13 months (end of treatment). The severity and incidence of acromegaly symptoms improved, while on octreotide capsules, compared to baseline.

“Acromegaly is a challenging disease, mostly requiring chronic injections of somatostatin analogs into the muscle or deep sub-dermal tissues by healthcare professionals, to maintain disease control. Currently available medications force most patients to plan their lives around the injections with regular visits to clinics just to receive treatment,” said Shlomo Melmed, M.D., senior vice president and dean, Cedars-Sinai Medical Center, Los Angeles and global study principal investigator. “These new results using a daily oral drug are an important advance for people with acromegaly.”

“The safety profile of octreotide capsules appears to be consistent with the known profile of injectable octreotide formulations, excluding injection site reactions,” stated Gary Patou, M.D., Chiasma’s senior medical advisor. “In fact, in this study, we saw the incidence of adverse events significantly decrease over time.”

“Chiasma is pleased with the results of this Phase III study being published in the current issue of JCEM, as they show the potential utility of octreotide capsules in the treatment of adults with acromegaly,” said Roni Mamluk, Ph.D., Chiasma’s chief executive officer. “If approved, octreotide capsules would be the first oral somatostatin analog, and would give people with acromegaly a unique alternative to chronic injections that are the current standard treatment for this lifelong disease.”

Based on these results, Chiasma intends to submit a New Drug Application to the FDA in 2015.

About The Study
The open-label, dose-titration, single-arm, baseline controlled, Phase III trial enrolled 155 people diagnosed with acromegaly and managed on somatostatin analogs. The study found 89% of patients were either completely or partially responding to parenteral treatment at baseline.

The goal of the oral treatment and primary endpoint was to assess the proportion of patients maintaining their baseline response at the end of the core treatment period and at the end of treatment. Response was defined similarly to the inclusion criteria as IGF-1 levels <1.3 times the ULN and integrated GH concentrations measured over two hours <2.5 ng/mL.

During the dose-titration phase of the study, patients initially received 40 mg (20 mg BID) daily of octreotide capsules, which could be increased, as required, to 60 mg/day or 80 mg/day (two 40 mg doses) to maintain clinical and biochemical response. The dose-titration phase was followed by a fixed-dose phase for up to 7 months; at that point, patients could elect to continue into a voluntary six-month extension phase up to 13 months.

Results showed:
– 62% of patients achieved disease control at the end of treatment.
– 85% of responders, at the end of the dose-titration phase, had sustained response up to 13 months.
– 80% of patients who entered the fixed-dose phase, improved or maintained their acromegaly symptoms (54% improved, 26% maintained), at the end of treatment.
– 86% who completed the core treatment period of seven months opted to participate in the voluntary six-month extension phase and continued using octreotide capsules.
– 89% of patients experienced an adverse event (AE); 92% of the events were mild to moderate. The most common AEs were reported in the gastrointestinal system, nervous system, and musculoskeletal system, consistent with the known safety profile of octreotide and the disease burden of acromegaly, with no AEs related to the oral route of administration. The majority of the gastrointestinal AEs reported in the study were mild to moderate, occurring within the first two months of treatment and resolved on treatment (median duration 13 days).
– 23 patients (14.8%) discontinued treatment due to AEs. Of these, 16 (69.6%) discontinued during the dose-titration phase. The most common AEs leading to discontinuation of the study drug were gastrointestinal symptoms, including nausea, diarrhea and abdominal pain. The incidence of AEs significantly decreased from the dose-titration phase to the fixed-dose phase and continued to decrease as exposure increased up to 13 months.

About Acromegaly
Acromegaly typically develops when a benign tumor of the pituitary gland produces too much growth hormone, ultimately leading to significant health problems and early death if untreated. Common features of acromegaly are facial changes, intense headaches, joint pain, impaired vision and enlargement of the hands, feet and tongue. Serious associated health conditions include diabetes, hypertension, cardiac and cerebrovascular disease and respiratory disorders.

Current treatment options include surgery to remove the tumor, radiation therapy which destroys any lingering tumor cells and/or medical treatment in cases where these approaches are not possible or fully effective. Medical treatments available currently include dopamine agonists, GH antagonists and injectable somatostatin analogs, the current standard of care. Currently available somatostatin analogs require large-bore needles, for injections into muscle (octreotide) or deep into the tissue underlying the skin (lanreotide).

Researchers estimate that three to four out of every million people develop acromegaly each year. According to the National Organization for Rare Disorders, acromegaly occurs in approximately 60 people per million in the United States. 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.

About Octreotide Capsules
Octreotide capsules are an investigational oral form of the peptide octreotide, a somatostatin analog that is currently available only by injection. Octreotide capsules uses a proprietary technology developed by Chiasma Inc., called Transient Permeability Enhancer (TPE®) that facilitates gastrointestinal absorption of unmodified drug into the bloodstream. Chiasma is independently leading the clinical and regulatory development and commercialization of octreotide capsules.

About Chiasma
Chiasma is developing oral drugs that have previously only been available by injection, thereby providing patients with pain-free medications that are self-administered. The Company’s lead candidate is octreotide capsules. Chiasma is evaluating additional proteins, peptides and small molecule drugs that that are currently only available by injection but could potentially be converted to oral delivery using the company’s TPE® technology. Chiasma is a Delaware corporation with a wholly owned Israeli subsidiary.

Additional information can be found at www.ChiasmaPharma.com.