First New Management for Poisonous Snakebites In Over 50 Years Is Now Available; Biotechnology Product Provides Safe and Effective Therapy For Poisonous Snake Bites

Savage Laboratories®, the pharmaceutical division of Altana Inc., announced today the availability of CroFab^TM; (Crotalidae Polyvalent Immune Fab -- Ovine) for prescription treatment of North American crotalid snake envenomation. CroFab^TM;, which is indicated for the management of patients with minimal or moderate North American crotalid envenomation, is the first product of its kind to be approved in over fifty years. Altana Inc. is the U.S. subsidiary of Byk-Gulden. CroFab^TM; was developed and manufactured by Protherics Inc. and will be marketed in the U.S. by Savage Laboratories.

"The availability of CroFab^TM; presents a safe treatment option for victims of venomous snakebites," said Richard C. Dart, MD, PhD, Director, Rocky Mountain Poison and Drug Center, Denver Health Authority and Associate Professor of Medicine, Surgery and Pharmacy, University of Colorado Health Sciences Center.

CroFab^TM®; consists of specific antibody fragments that bind to toxic substances in the venom of most crotalids. CroFab^TM; works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body. CroFab^TM; was effective in neutralizing the venoms of 10 clinically important North American crotalid snakes in a murine lethality model. Two clinical trials of CroFab^TM; were conducted. In the larger, more recent study 31 patients were administered an initial dose of six vials CroFab^TM; with an additional dose of six vials followed by two vial doses every six hours for up to 18 hours, if deemed necessary by the investigator. All 31 patients achieved initial control of their envenomation. None of the patients experienced anaphylactic or anaphylactoid response as a result of the administration of CroFab^TM;. Several mild to moderate side effects did occur, such as rash, urticaria and pruritis (allergic reactions), and are listed in the CroFab^TM®; Warnings and Precautions" section of the package insert labeling.

"We are very excited to be able to offer a safe and effective treatment for poisonous snakebites," said George Cole, President, Savage Laboratories.

Prevalence of Snakebites
Approximately 7,000 to 8,000 of all snakebites involve venomous species of snakes, resulting in 12 to 15 fatalities each year. Poisonous snakebites in the United States predominantly involve the crotalid snakes. The most common side effect of envenomation is local tissue destruction, but severe coagulation abnormalities, other systemic side effects (hypertension, pulmonary edema, cardiovascular collapse and renal failure), and appendage loss can occur(1).

“The administration of an antivenin is important not just for saving lives, but for avoiding serious tissue and bleeding complications," said Richard Clark, MD, Director of Medical Toxicology University of California San Diego Medical Center and Medical Director, San Diego Division, California Poison Control Systems. "Untreated venomous snakebites can cause permanent disability and damage including loss of limb.”

CroFab^TM Administration
CroFab^TM; is indicated for the management of patients with minimal or moderate North American crotalid envenomation. The administration of CroFab^TM; antivenin should be initiated as soon as possible (within six hours) after poisonous snakebites in patients who develop signs of progressive envenomation, i.e. worsening of local injury, coagulation abnormality, or systemic signs of envenomation. The product is intended for intravenous administration after reconstitution with 10 mL of Sterile Water for Injection USP (diluent not included). The recommended number of vials will vary for each patient. In clinical trials the best results were achieved with an initial dose of six vials with the option to retreat with additional vials in 6-vial increments, followed by two vial doses every six hours for up to 18 hours.

CroFab™ Production and Delivery
CroFab^®; is a preparation of ovine monovalent immunoglobulin (Fab) fragments obtained from the blood of healthy sheep flocks immunized with one of the following North American snake venoms: Crotalus atrox (Western Diamondback rattlesnake), Crotalus adamanteus (Eastern Diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake) and Agkistrodon piscivorus (Cottonmouth or Water Moccasin). Each batch of monospecific antivenin is prepared by fractionating the immunoglobulin from the ovine serum, digesting the antibodies with papain, and isolating the venom-specific Fab fragments on ion exchange and affinity chromatography columns. This proprietary process purifies the antivenin and discards unneeded portions of the antibodies. CroFab^TM; is the first antivenin to be purified by such a process. To obtain the final antivenin, the four different monospecific antivenins are mixed. CroFab^TM; is shipped in vials as a sterile, non-pyrogenic, purified, lyophilized preparation intended for intravenous administration. Each vial contains up to 1.0 g of total protein and not less than the indicated number of mouse LD50 neutralizing units.

CroFab™ Warnings and Precautions
The majority of adverse reactions to CroFab^TM; reported in clinical studies were mild or moderate in severity -- primarily rash, urticaria and pruritus. CroFab^TM; should not be administered to patients with a known history of hypersensitivity to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available. It is not known whether CroFab^TM; is excreted in human breast milk so caution should be exercised when CroFab^TM; is administered to a nursing woman. Adverse events involving the skin and appendages were reported in 14 of the 42 patients. Three of the 25 patients who experienced adverse reactions experienced severe or serious adverse reactions. All adverse reactions resolved during the course of treatment. Full prescribing information is enclosed with the product and is available at http://www.savagelabs.com.

CroFab™ History
CroFab^TM; was developed by Protherics Inc. (formerly Therapeutic Antibodies, Inc.) and was approved by the Food and Drug Administration on October 2, 2000. CroFab^TM;) was given Orphan Drug Designation by the Food and Drug Administration on January 12, 1994. The product will be manufactured at Protherics' facility in Blaenwaun, Wales and marketed in the United States by Savage Laboratories. Protherics' ordinary shares are listed on the Official List of the UK Listing Authority and are traded on the London Stock Exchange under the symbol PTI.L.

This press release contains forward-looking statements. Any statements contained in this press release that are not historical facts are forward-looking statements as defined in the U.S. Private Securities Litigation Reform Act of 1995.

About Savage Laboratories

Located in New York, Savage Laboratories is the ethical pharmaceutical division of Altana Inc., the U.S. subsidiary of Byk-Gulden, a multi-national pharmaceutical company based in Konstanz, Germany. Savage Laboratories develops and markets products for use in dermatology, obstetrics/gynecology, emergency medicine, critical care, and pulmonary medicine. In addition to marketing products in the Savage Laboratories(R) and Byk-Gulden R&D pipelines, Savage Laboratories acquires and/or co-promotes products targeted to critical care, pulmonary, and emergency room physicians.

SOURCE Savage Laboratories
CONTACT: Jackie Beltrani of Savage Laboratories, 631-454-7677; or Russell LaMontagne of Corinth Group Communications, for Savage Laboratories(R),
212/255-5340

Copyright 2001 PR Newswire Association, Inc. January 31, 2001, Wednesday