An oral formulation of salmon calcitonin based on Emisphere Technologies' eligen delivery system has entered Phase III clinical trials for the treatment of osteoarthritis.
Novartis Pharma, which also has licence agreements with Emisphere for eligen formulations of human growth hormone and parathyroid hormone, is pursuing the Phase III programme in the European Union and the US through its development partner Nordic Bioscience.
The aim is to recruit more than 2,000 patients to the trials. The oral version of salmon calcitonin (SMC021) is already in Phase III trials for the treatment of osteoporosis.
The synthetic salmon calcitonin used in these formulations is currently available only as a nasal spray or in injectable form. Oral calcitonin could also be the first ever disease-modifying drug for the treatment of osteoarthritis, exerting a protective effect in at-risk or already affected joints to help maintain the quality of cartilage and reduce the progression of joint-space narrowing, Emisphere suggests.
The formulation comprises salmon calcitonin and 5-CNAC, a delivery agent for increasing gastrointestinal absorption, incorporated into tablet form with Emisphere's eligen technology. The US company's delivery system facilitates the transport of proteins, peptides or macromolecules across biological membranes such as the small intestine, without altering their chemical form or biological integrity.
The eligen technology uses as drug carriers a library of more than 4,000 proprietary synthetic chemical compounds, referred to as Emisphere delivery agents. These have no known pharmacological activity themselves at the intended clinical dose levels, Emisphere says.
Using the body's natural passive transcellular transport process, the selected and customised delivery agent takes the orally ingested compound across the relevant cell membrane, then dissociates from the drug molecule, which subsequently re-establishes its natural shape or conformation and returns to its therapeutically active state, Emisphere explains.
Studies have shown that the process does not involve chemical modification of the drug molecule, while the integrity of the cell membrane and cytoskeletal structure are maintained, it adds.
According to Emisphere, the system has been used for oral delivery of a range of molecules varying in size from 500 Daltons to more than 150,000 Daltons. Oral formulations created with the eligen technology include tablets, solutions and capsules; Emisphere believes it is also applicable to controlled-release dosage forms.
The US company signed the licence agreement with Novartis Pharma for the development of oral salmon calcitonin in 2000. The two companies tied up for the development of oral human growth hormone and an oral form of parathyroid hormone fragment 1-34 in 2004 and 2006 respectively.
In November 2004, Emisphere signed the first licensing agreement for use of its eligen technology with small molecule compounds, partnering with Novartis' Swiss rival Roche. Emisphere's pipeline also includes a collaboration with Genta, for an oral version of gallium as anticancer therapy, and a number of compounds that Emisphere is developing itself.
The most advanced of these latter projects are oral heparin (Elaprin), which is expected to enter a Phase III trial shortly for the prevention of venous thromboembolism following elective total hip replacement; and oral insulin, in Phase II for the treatment of type 2 diabetes.