Chiasma Inc.'s Octreolin(TM) (Oral Octreotide) Shown to Inhibit Growth Hormone in Healthy Subjects
Published: Jun 06, 2011
NEW YORK and JERUSALEM, June 6, 2011 /PRNewswire/ -- Chiasma, Inc., a privately held biopharma company, presented pharmacology results from clinical studies at the 12th International Pituitary Congress showing that Octreolin, a proprietary investigational new oral formulation of octreotide, demonstrated a consistent pharmacokinetic (PK) profile similar to that of subcutaneously injected octreotide acetate. Most important, the data illustrated that Octreolin reduced growth hormone (GH) levels, a clinical endpoint that has been used for approval in other drugs for acromegaly.
Chiasma is developing Octreolin as an oral treatment for acromegaly and anticipates that a Phase 3 trial in patients will begin enrollment later in 2011.
Pharmacodynamic data presented at the Congress demonstrated that a single dose of Octreolin administered to healthy subjects significantly suppressed both basal GH secretion and Growth Hormone Releasing Hormone (GHRH)-stimulated GH secretion by about 80%. Inhibition was recorded in all 18 subjects receiving Octreolin as compared to their GH levels without Octreolin. The mean reductions in both basal and stimulated GH levels were statistically significant (P<0.001).
In addition, the presentation summarized results from three clinical studies with Octreolin. These data showed that:
- Octreolin was absorbed after oral administration within 1 hour;
- There was a reproducible linear dose-dependent relationship for the 3 doses studied;
- An oral dose of Octreolin 20 mg provided similar systemic exposure to octreotide 0.1 mg given via subcutaneous (SC) injection;
- The drug was well tolerated with no significant clinical or preclinical adverse events;
- Side effects of Octreolin were comparable to those of injectable octreotide.
Octreolin utilizes the Company's proprietary Transient Permeability Enhancer (TPE) technology, which enables previously injectable-only drugs to be taken orally.
Sam Teichman, MD, Chiasma's Chief Medical Officer and presenter at the Congress said, "In addition to the GH reducing effect observed in the trial conducted in the United States under an Investigational New Drug (IND), no significant Octreolin or TPE-related adverse findings were reported in two toxicology studies in primates and, therefore, the No Adverse Event Level (NOAEL) was established at the highest Octreolin dose tested. This clean safety profile paves the way for further Octreolin development with chronic therapy in patients and continues the validation of the safety profile of the underlying technology platform.
"If the results of the Phase 3 program are positive, the Company intends to submit a New Dug Application (NDA) using the 505(b)(2) NDA regulatory pathway in the U.S. and its European Medicines Agency (EMA) equivalent, the Hybrid Application, in Europe."
How Octreolin Works
Octreolin is a product in capsule form that contains octreotide acetate, a 1.0 kDa peptide and the Company's proprietary TPE technology. The TPE system allows its drug cargo to cross mucosal epithelia in the small intestine by inducing a temporary opening of the Tight Junctions that seal and regulate passage (the paracellular route) between cells. This effect on the epithelia is rapid and fully reversible. The drug reaches the bloodstream effectively in its native active form.
TPE activity is the result of a proprietary combination of excipients assembled in a process leading to a suspension of hydrophilic particles in a lipophilic medium. Chiasma has developed a unique, simple and cost effective production process that seeks to maximize safety and stability of its drug products; all components used in manufacturing of the drug product are approved for pharmaceutical use. The TPE technology is versatile, can be applied to a wide range of therapeutic agents and requires no chemical modification of the drug.
Acromegaly is an endocrine condition associated with a benign adenoma in the pituitary gland that secretes excess GH, which stimulates excess production of insulin-like growth factor 1 (IGF-1) by the liver, causing tissue growth throughout the body. Even well-controlled patients have an increased risk for mortality; and in poorly controlled patients, cardiovascular, respiratory, endocrine, and metabolic morbidities result in standardized mortality ratios of 2.5 when compared to nonacromegaly populations.(1)
Injectable (subcutaneous and intramuscular) somatostatin analogs, which bind to somatostatin receptors (SSTR2, SSTR5) to inhibit GH secretion are the therapeutic standard of care for acromegaly patients who are not cured by resection of the tumor; surgery is the first line of treatment. GH inhibition by octreotide, the most commonly used somatostatin analog in clinical use, reduces or reverses morbidity and mortality associated with acromegaly. There is a well-defined correlation between plasma levels of octreotide and reduction in GH and IGF-1 levels. Clinical endpoints include suppression of GH and normalization of IGF-1 levels.(2)
Treatment with Sandostatin LAR® (depot formulation of octreotide acetate), a monthly IM injection, is the most common treatment of choice for life. Octreotide is effective for 95% of the patients; approximately 65% and 30% of patients show a complete or partial response, respectively. However, the injections cause discomfort and pain, with 30% to 50% of patients reporting pain at the injection site (for doses of 20 mg and 30 mg Sandostatin LAR). Patients can also suffer from welts that take a considerable period of time to disappear. In addition, patient needle-phobia can manifest itself in non-compliance as well as stress and anxiety for those who ultimately do take the injections. Furthermore, the octreotide longacting injections require complex reconstitution and caregivers' assistance, frequently necessitating visits to physician offices.
The pool of acromegaly patients eligible for Octreolin treatment is estimated to be approximately 15,000 in the U.S. and an equal number in Europe.
Chiasma applies its proprietary technology to approved drugs, which not only enables their being converted from injectable to oral, but importantly can result in the development of new indications. The Company's TPE technology promotes the delivery of drugs to the GI wall and from there to the liver. It is applicable to macromolecules that to-date can be administered only by injection and can be utilized also with small molecules that are already orally available but are poorly absorbed.
Chiasma is a Delaware corporation with a 100% owned Israeli subsidiary.
Additional information can be found at: www.ChiasmaPharma.com.
This press release contains forward-looking statements about the business, goals and prospects of Chiasma, Inc., including, without limitation, statements about the development of drugs in the TPE system. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. Chiasma is under no obligation, and expressly disclaims any obligation, to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.
(1) Melmed et al., Guidelines for Acromegaly Management, J Clin Endocrinol Metab, May 2009, 94(5):1509-1517
(2) Sandostatin, octreotide acetate, Injection, Rx Only, Prescribing Information
SOURCE Chiasma, Inc.