HAYWARD, Calif., June 29 /PRNewswire/ -- Acologix, Inc., a privately-held biopharmaceutical company, announced today that the Company presented Phase II clinical study data of AC-100, its novel synthetic peptide derived from an endogenous human protein produced by bone and dental cells. The data demonstrated that AC-100 stimulated the formation of new dentin (the hard tissue of teeth that protects the tooth pulp and supports the outer enamel) when applied to tooth defects. The data was presented as an oral presentation at the Annual Meeting of the International Association for Dental Research (IADR) in Brisbane, Australia. This was a more complete presentation of the study results following a short presentation on the study made at the Late Breaking session of the American Association for Dental Research Annual Meeting in March 2006.
Each year, more than 160 million dental restoration procedures are performed in the United States. Drilling during these procedures irritates the dental pulp and reduces the dentin layer that protects the pulp, causing pain and sensitivity, and sometimes leading to complications, including tooth loss.
Phase 2 Study Design and Results
The randomized, double-blind, placebo-controlled trial enrolled 35 patients who were candidates for at least two third-molar (wisdom teeth) extractions. Patients served as their own controls, with one molar treated with 200 ug AC-100 (applied on days 0, 2 and 4 through the dentin tubules) and the other with a placebo. After two months, the teeth were extracted and evaluated for remaining dentin thickness (RDT), new dentin formation, inflammation and necrosis. Administration of AC-100 resulted in a clear trend in the formation of new dentin compared to placebo. This effect was seen across a wide variety of cavity depths. Importantly, the efficacy of AC-100 was seen most dramatically in the deepest cavities (RDT < 0.5 mm), where the clinical utility of the approach is most needed. AC-100 was well tolerated in the study with no increase in inflammatory response, necrosis, pulpitis (inflammation of the pulp) or other complications observed in AC-100-treated teeth compared with placebo-treated teeth. No serious adverse events were reported.
In addition, preclinical data on dentin and bone regeneration was presented as a poster presentation at the IADR. In this study, an indirect pulp capping and a tooth extraction model in animals were used to evaluate the effects of AC-100 on new dentin and bone formation, tissue healing and bone quality, respectively.
In the indirect pulp capping portion of this study AC-100 induced new dentin growth comparable to and better than Dycal in a dose and application method dependent manner. Importantly, AC-100 achieved its activity in a tissue protective manner, stimulating the existing pulp cells to produce dentin while completely abolishing pulp inflammation and decreasing the number of apoptotic cells in the pulp. This reduction in pulp irritation responses gives an indication of possible favorable effects of AC-100 on short-term postoperative tooth sensitivity due to pulp irritation.
In the bone regeneration portion of the study following extraction, tooth sockets were filled with a collagen sponge containing AC-100 at two different doses or a collagen sponge soaked in saline (control group). New bone formation and bone quality were evaluated 28 days later. Application of AC-100 resulted in a significant and dose-dependent improvement in the quality of new bone formed. The groups treated with AC-100 at the two different doses had bone quality scores approximately two and three times higher than controls, respectively. Giving an indication of a favorable safety profile, the degree of inflammation was lower in the AC-100-treated groups than in the control group, although not statistically significant.
Acologix is studying AC-100 for a variety of hard tissue applications including periodontal, oral bone, dental implant and orthopedic applications.
Acologix, a privately held biopharmaceutical company, is developing and commercializing innovative biopharmaceuticals targeting osteo-renal diseases, including chronic kidney disease, renal osteodystrophy, bone repair and regeneration, periodontal disease, general dentistry and oral care. Acologix is partnering with Toray Industries, Inc. of Japan on the development and commercialization of TRK-820 for the treatment of uremic pruritus in dialysis patients. TRK-820 is being studied in a European Phase 3 pivotal clinical trial, with a Phase 3 trial planned to launch in the United States. AC-100 (Dentonin(R)), a novel small peptide with dental, periodontal and orthopedic applications, is currently being studied in two Phase 2 clinical studies, one in dental restoration procedures and another for the repair of periodontal defects. Acologix is also developing AC-200 (Phosphatonin) to treat hyperphosphatemia and subsequent clinical problems associated with chronic kidney disease. For more information go to www.acologix.com.
Abstract # 0545: "AC-100, Novel Biological Approach to Promoting Dentin Formations in Humans," by Mirella Lazarov, D.D.S., Ph.D., Jere D. Fellmann, Ph.D., and David M. Rosen, Ph.D. of Acologix; Pamela DenBesten, D.D.S., M.S., of University of California, San Francisco, School of Dentistry; and Cornelis Pameijer, D.M.D., D.Sc., Ph.D., of the University of Connecticut, School of Dental Medicine. Presented by Dr. Lazarov on June 29, 2006 at the Annual Meeting of the International Association for Dental Research in Brisbane, Australia
Abstract #0268: "AC-100, A Novel Biological Agent for Dentin and Bone Regeneration," by Mirella Lazarov, D.D.S., Ph.D., David M. Rosen, Ph.D. of Acologix; Mei-Shu Shih, Ph.D., A. Negron of SkeleTech; and Veronica Kiklevich, D.V.M., Michael Powers, D.V.M., of the Department of Veterinary Clinical Sciences, Washington State University. Poster presented on June 28, 2006 at the Annual Meeting of the International Association for Dental Research Brisbane, Australia.