More Convenient Dosing and Enhanced Safety Demonstrated in Phase I Study of ISIS 104838
Thursday April 5
Source: PR Newswire
CARLSBAD, Calif., April 5 /PRNewswire/ -- Isis Pharmaceuticals (Nasdaq: ISIP) announced today favorable results from the first systemic human clinical trials of an antisense drug derived from Isis' proprietary second-generation chemistry. Results from Phase I safety studies of the intravenous (IV) and subcutaneous (SQ) delivery of ISIS 104838 demonstrated that these advanced antisense drugs offer patients a more convenient dosing schedule of once every 2 to 4 weeks as well as safety advantages over first-generation antisense drugs. The SQ study demonstrated substantial improvement in local tolerability over first-generation antisense drugs. ISIS 104838, a novel antisense inhibitor of TNF-alpha, is being developed in IV and SQ formulations for the treatment of rheumatoid arthritis (RA), and in a topical cream formulation for psoriasis.
In each of the IV and SQ Phase I trials, multiple doses of ISIS 104838 were studied in healthy volunteers. In the IV trial, we determined the elimination half-life to be 13.7 days consistently across all doses. Most notably in the SQ trial, the maximum dose of 6 mg/kg was well tolerated, with no swelling of local lymph nodes observed at any dose. Injection site reactions observed were mild at all doses studied.
"We have developed a broad understanding of the pharmacokinetic properties of both first- and second-generation chemistry antisense drugs through extensive study in animal models, and it is very gratifying to see the preclinical data confirmed in humans," said Andrew Dorr, M.D., Isis' Vice President and Chief Medical Officer. "We expected to see an elimination half-life of about 2 weeks for these drugs, and that is what was achieved. These data support IV dosing as infrequently as monthly, which is a very competitive dosing schedule relative to drugs on the market, and a tremendous improvement over the every-other-day dosing regimen of first-generation antisense drugs. Perhaps more importantly for patients, the performance of subcutaneous administration of this second-generation antisense drug was sufficiently favorable that IV administration may be altogether unnecessary."
"With the enhanced potency, safety and dosing convenience we've seen demonstrated in animal models, we believe our second-generation drugs have the potential to be highly competitive," stated Stanley T. Crooke, M.D., Ph.D., Isis' Chairman and CEO. "Based on these results and other on-going studies, we will be able to select the most suitable administration route for the patient: intravenous, intravitreal, subcutaneous, topical, or oral."
Isis is currently developing 5 second-generation products, which treat rheumatoid arthritis, psoriasis, diabetes, diabetic retinopathy and multiple sclerosis. Advances in second-generation chemistry have substantially broadened the opportunity for antisense drugs.
An oral formulation of ISIS 104838 is in development by Orasense(TM) Ltd., a joint venture between Isis and Elan Corporation plc., of Dublin, Ireland. The goal of the Orasense collaboration is to create a technology platform for the oral delivery of antisense drugs.
TNF-alpha, or tumor necrosis factor alpha, is a naturally occurring cytokine that is implicated in the development and progression of many inflammatory, infectious and autoimmune diseases. It is a validated target in RA, where it plays a major role in the pathology of joints. TNF-alpha stimulates bone and cartilage to be absorbed, facilitates inflammation and inhibits bone formulation. High levels of TNF-alpha are present in patients with RA. Presently, the market for intravenous TNF-alpha drugs is greater that $500 million and is growing. There are approximately 1.2 million patients with RA in the U.S.
Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs. The company has commercialized its first product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in AIDS patients. In addition, Isis has 11 products in its development pipeline, six of which are in Phase II human clinical trials. Isis has a broad and proprietary patent estate of nearly 700 issued and allowed patents worldwide. Isis' GeneTrove(TM) division uses antisense to assist pharmaceutical industry partners in validating and prioritizing potential gene targets through customized services and access to an extensive gene function database. Ibis Therapeutics(TM) is a division focused on the discovery of small molecule drugs that bind to RNA.
This press release contains forward-looking statements pertaining to Isis Pharmaceuticals, Inc.'s drug discovery and development activities. Such statements are subject to certain risk factors and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that can be proven to be safe and effective for use as human therapeutics and the endeavor of building a business around such potential products. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those described in Isis' Annual Report on Form 10K-A for the year ended December 31, 2000, which is on file with the U.S. Securities Exchange Commission.
Vitravene(TM) is a trademark of Novartis AG. GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis Pharmaceuticals, Inc.
Source: Isis Pharmaceuticals
Contact: Karen Lundstedt, Corporate Communications of Isis Pharmaceuticals, 760-603-3880