TARRYTOWN, N.Y., Dec. 12 /PRNewswire-FirstCall/ -- Emisphere Technologies, Inc. today announced that positive clinical data generated by Drs. Daniel Manicourt and Jean-Pierre Devogelaer from the Department of Rheumatology at the University Hospital St-Luc, Universite Catholique de Louvain, Brussels, Belgium evaluating oral salmon calcitonin (CT) supplied by Novartis Pharma AG using Emisphere’s eligen(R) technology in treating osteoarthritis (OA) were presented at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston. Results of this study strongly suggest that Oral CT (enabled by Emisphere’s proprietary eligen(R) technology licensed to Novartis for the use with calcitonin) exhibits not only clinical efficacy but also reduces markedly the levels of several biochemical markers of joint metabolism, which all have been shown to have a pejorative prognostic value of the OA disease process in longitudinal studies including large cohorts of patients.
The randomized, double-blind, placebo-controlled, parallel study was conducted for 3 months in OA patients to assess the efficacy of this novel form of CT in patients suffering from knee OA. Patients received daily either a placebo (n=16), 0.5 mg of oral CT (n=17) or 1 mg of oral CT (n=18).
Clinical Efficacy
Clinical efficacy on pain, function and stiffness were evaluated by Lequesne’s algofunctional indices (LI).
In the placebo group, there was no significant change in the mean +/- SD value of LI. In the 2 CT groups, the mean value of LI was similar at day 0 (15.4 +/- 2.6), and was significantly decreased at day 84 (10.6 +/- 3.8 in the 0.5 mg group, and 9.6 +/- 3.2 in the 1 mg group).
Biochemical Parameters of Joint Metabolism
Biochemical parameters of joint metabolism, as assessed by enzyme immunoassays, included urinary levels of type I and type II collagen C telopeptide (CTX-I and CTX-II, respectively) as well as serum levels of type II collagen neoepitope C2C, matrix metalloproteinase (MMP)-3, collagenase-3 (MMP-13), tissue inhibitors 1 and 2 MMPs (TIMP-1 and TIMP-2) and hyaluronan (HA). Statistical analysis included analysis of variance followed by Tukey test whenever needed.
When compared to values at study entry, levels of biochemical parameters had changed significantly in all groups at day 84 (p<0.05 to 0.01). In the placebo group, there was a significant increase in the mean urinary levels of both CTX-1 (15%), CTX-II (9%) and in the mean serum levels of C2C (29%), MMP-13 (153%), MMP-3 (49%) and HA (25%). In contrast in the 1 mg CT group, there was a significant decrease in the mean urinary levels of both CTX-1 (10%), CTX-II (21%) as well as in the mean serum levels of C2C (25%), MMP-13 (40%), MMP-3 (18%) and HA (28%). Results obtained in the 0.5 mg CT group were intermediate between the other groups and are not reported. No change in the mean serum levels of TIMP-1 and TIMP-2 was observed in the 3 groups.
Study Withdrawals
The number of withdrawals was 2 in the placebo group (lack of efficacy), 4 in the 0.5 mg CT group (1 for lack of efficacy and 3 for nausea and headache), and 4 in the 1 mg CT group (2 for protocol violation and 2 for nausea and headache).
“This pilot study, conducted by the University Hospital St-Luc, Universite Catholique de Louvain, Brussels Belgium demonstrated the ability of the 1 mg dose of our unique oral salmon calcitonin product to not only show clinical efficacy in the study, but also demonstrated a decrease in biochemical markers that have been correlated with continued joint degradation. Over the course of the 84-day study, the placebo patients had no statistically significant change in clinical scores while they had statistically significant increases in biochemical markers that have been correlated with continued joint degradation. We are encouraged by these results and look forward to Novartis commencing pivotal Phase III studies of Oral CT in early 2006,” said Michael M. Goldberg, M.D., Chairman and Chief Executive Officer of Emisphere Technologies. “The success of Oral CT in this Phase II study provides hope for the tens of millions of patients worldwide suffering with OA. There are currently no proven pharmaceutical products that can impact on the progression of this chronic disease. Nordic Bioscience presented two additional papers at the OARSI conference that further elucidate the mechanism by which oral calcitonin positively impacts on OA progression.”
About Osteoarthritis
Osteoarthritis is a joint disease that mostly affects cartilage. Cartilage is the slippery tissue that covers the ends of bones in a joint. Healthy cartilage allows bones to glide over each other. It also helps absorb shock of movement. In OA, the top layer of cartilage breaks down and wears away. This allows bones under the cartilage to rub together. The rubbing causes pain, swelling, and loss of motion of the joint. Over time, the joint may lose its normal shape. Also, bone spurs may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space, which causes more pain and damage.
People with OA often have joint pain and reduced motion. Unlike some other forms of arthritis, OA affects only joints and not internal organs. Rheumatoid arthritis -- the second most common form of arthritis -- affects other parts of the body besides the joints. OA is the most common type of arthritis.
About the eligen(R) Technology
Emisphere’s broad-based oral drug delivery technology platform, known as the eligen(R) technology, is based on the use of proprietary, synthetic chemical compounds, known as Emisphere delivery agents, or “carriers.” These molecules facilitate or enable the transport of the therapeutic macromolecules across biological membranes such as those of the gastrointestinal tract, and exert their desired pharmacological effect. The Emisphere(R) delivery agents have no known pharmacological activity themselves. Emisphere’s eligen(R) technology makes it possible to orally deliver a therapeutic molecule without altering its chemical form or biological integrity. Emisphere is pursuing shortened registration timelines for currently marketed drug products whose absorption following oral administration is improved using the eligen(R) technology through supplemental New Drug Applications or 505(b)(2) filings with the US FDA. Successful achievement of these regulatory strategies may not require large-scale studies to support product registration.
About Emisphere Technologies, Inc.
Emisphere Technologies, Inc. is a biopharmaceutical company pioneering the oral delivery of otherwise injectable drugs. Emisphere’s business strategy is to develop oral forms of injectable drugs, either alone or with corporate partners, by applying its proprietary eligen(R) technology to those drugs or licensing its eligen(R) technology to partners who typically apply it directly to their marketed drugs. Emisphere’s eligen(R) technology has enabled the oral delivery of proteins, peptides, macromolecules and charged organics. Emisphere and its partners have advanced oral formulations or prototypes of salmon calcitonin, heparin, insulin, parathyroid hormone, human growth hormone and cromolyn sodium into clinical trials. Emisphere has strategic alliances with world-leading pharmaceutical companies. For further information, please visit http://www.emisphere.com.
Safe Harbor Statement Regarding Forward-looking Statements
The statements in this release and oral statements made by representatives of Emisphere relating to matters that are not historical facts (including without limitation those regarding the timing or potential outcomes of research collaborations or clinical trials, any market that might develop for any of Emisphere’s product candidates and the sufficiency of Emisphere’s cash and other capital resources) are forward-looking statements that involve risks and uncertainties, including, but not limited to, the likelihood that future research will prove successful, the likelihood that any product in the research pipeline will receive regulatory approval in the United States or abroad, the ability of Emisphere and/or its partners to develop, manufacture and commercialize products using Emisphere’s drug delivery technology, Emisphere’s ability to fund such efforts with or without partners, and other risks and uncertainties detailed in Emisphere’s filings with the Securities and Exchange Commission (the “SEC”), including those factors discussed under the caption “Risk Factors” in Emisphere’s Annual Report on Form 10-K (file no. 1-10615) filed on March 11, 2005, as amended by Form 10-K/A filed on March 29, 2005.
Emisphere Technologies, Inc.
CONTACT: Elliot M. Maza, CPA, J.D., Chief Financial Officer,+1-914-785-4703, or Gillian Racine, Investor Relations, +1-914-785-4742,gracine@emisphere.com, both of Emisphere Technologies, Inc.; or Media: DanBudwick of BMC Communications, +1-212-477-9007 ext.14, for EmisphereTechnologies, Inc.
Web site: http://www.emisphere.com/
