Centocor Inc. announced Tuesday that it has signed anagreement with the Japanese company Tanabe Seiyaku Co. Ltd.for the clinical development and marketing of CenTNF in Japan.
CenTNF is Centocor's (NASDAQ:CNTO) chimeric monoclonalantibody to tumor necrosis factor that it has been developingas a treatment for rheumatoid arthritis and inflammatorybowel diseases such as Crohn's disease. Centocor has alreadysponsored Phase I and II clinical trials of CenTNF in Europe forboth indications.
Under the terms of the agreement, Tanabe will pay Centocor alump sum (undisclosed) for its prior research and developmentefforts on the drug. Tanabe will also take the drug throughJapanese clinical trials, and both parties will file jointly formarketing approval with the Japanese Ministry of Health andWelfare. Thereafter, Centocor will manufacture the finishedproduct for Tanabe's exclusive distribution in Japan.
"Based on encouraging Phase I and II clinical results of CenTNFin rheumatoid arthritis and Crohn's disease, we are anxious tomove forward with studies in Japan," said David Holveck,Centocor's president and chief executive officer. "We expect tostart a Phase III study in Europe next year."
The Phase I/II clinical trial on CenTNF was conducted in theNetherlands at the Academisch Medisch Centrum, explainedBobba Venkatadri, executive vice president of Centocor'spharmaceutical business. In that trial, 10 patients with Crohn'sdisease were given a 10 milligram per kilogram body weight(mg/kg) dose of CenTNF. All 10 responded positively to thetreatment, he said.
The Phase II trial on CenTNF for treating rheumatoid arthritis(RA) was conducted in the United Kingdom at the KennedyInstitute of Rheumatoid Arthritis. This trial enrolled 20patients who had failed all previous therapies for RA, and 19 ofthem responded to the CenTNF treatment (the 20th turned outto be suffering from other, underlying maladies as well).
Again, the patients were dosed with 10 mg/kg of the chimericmonoclonal antibody, but in this protocol they received a singledose every 12-16 weeks because the researchers found that"the effect lasts that long," said Venkatadri.
And the effect was dramatic. Normally, patients with such anadvanced form of RA can barely move; it can take them five tosix hours to get out of bed. But after treatment with CenTNF, inall cases, the patients were able to get up and walk in 30-45minutes, Venkatadri told BioWorld. The researchers measuredboth biological and psychological indicators (there can be astrong placebo effect) to determine the drug's effects, he added.
Some individuals were dosed four to five times, but noneexhibited any immunological responses to the drug (whichbeing chimeric, is about one-third mouse sequences),Venkatadri said.
"Based on these results, we just started another 72 patients inan expanded Phase II double-blind study at the U.K.'s KennedyInstitute," he said. Other centers are being registered presently.
Centocor also intends to conduct further clinical trials onCenTNF for Crohn's disease in the U.S. and Europe. In fact, thecompany is submitting an investigational new drug (IND)application to the U.S. FDA for those trials "imminently,"Venkatadri told BioWorld.
Tanabe is Centocor's third major partner in the pharmaceuticalarena. Centocor joined the British pharmaceutical giantWellcome plc in September to develop and bring to marketCentocor's oncology products -- especially Panorex, amonoclonal antibody-based therapeutic for treating colorectalcancer.
And Centocor of Malvern, Pa., has an ongoing relationship withEli Lilly and Co. regarding its cardiovascular anti-coagulantdrug CentoRx (a monoclonal antibody designed to bind tosurface receptors on blood platelets; it has cleared Phase IIItrials in coronary angioplasty and is still in the clinic fortreating unstable angina) and its star-crossed sepsis drugCentoxin (or HA-1A, an anti-endotoxin antibody, whichCentocor has in clinicals for treating fulminantmeningococcemia in children).
Centocor also has a new partner for its diagnostics. In lateSeptember it granted Mallinckrodt Medical Inc. the exclusiverights to market and sell Myoscint -- a radiopharmaceutical fordetecting myocardial necrosis following heart attacks -- inEurope, the Middle East and Africa.
Centocor intends to round out 1993 by filing in Germany forapproval to market Panorex and in the U.S. for approval tomarket CentoRx, Holveck told BioWorld. In 1993, "we've hit allour financial and qualitative targets," he said. "We're positionedwith good partners, we've cut our expenses (the burn rate willbe down to $5 million for the fourth quarter) and we're filingfor regulatory approval for Panorex and CentoRx." Moreover, headded, "we'll go into 1994 with $130 million in the bank."
The company's stock closed at $12.88 a share on Tuesday,down 63 cents.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.