Clinical Trials Roundup—Week of 6/7

Entropin to Test Double-Strength Esterom in Phase III Trial
Entropin Inc. (Woodland Hills, CA) plans to test a new double strength formulation of Esterom in its forthcoming Phase III Clinical Trial. This new formulation could extend the Esterom family of products to address range of motion disorders/sprains including acute/chronic back and shoulder sprain/strain and associated pain.

Esterom is a unique topical preparation for the treatment of impaired range of motion. A successful Phase II Clinical trial was completed showing both safety and efficacy in the treatment of acute lower back sprain, and acute painful shoulder.

For more informatin: Higgins Bailey, Interim CEO, Entropin Inc., 21550 Oxnard St., Suite 810, Woodland Hills, CA 91367. Tel: 818-340-2323. Fax: 818-340-3006.

Matrix Extends Enrollment in Phase II Trial of IntraDoseMatrix Pharmaceutical Inc. (Freemont, CA) has completed the planned enrollment in a Phase II trial of IntraDose Injectable Gel in primary liver cancer (HCC), and has extended enrollment in view of the encouraging results seen to date. Thirty-seven patients, the original enrollment target, have been entered on study at medical centers in the US, France, Germany, and Hong Kong. Total enrollment is now projected to be 45–55 patients.

IntraDose (cisplatin/epinephrine) Injectable Gel delivers cisplatin, a common anticancer drug, directly into tumors. The cisplatin is delivered in a collagen-based gel that also contains epinephrine. IntraDose delivers much higher concentrations of cisplatin into the tumor than can be administered intravenously and facilitates the retention of drug in the tumor for several hours.

For more information: Richard D. Leavitt, Senior VP, Medical and Regulatory Affairs, Matrix Pharmaceutical Inc., 34700 Campus Dr., Fremont, CA 94555. Tel: 510-742-9900. Fax: 510-742-8510.

Centocor Completes Successful Phase III Trial of Remicade
In a Phase III clinical trial, Centocor Inc.'s (Malvern, PA) Remicade (infliximab) produced significant reductions of signs and symptoms of advanced rheumatoid arthritis (RA) that were sustained or further reduced from 30 weeks through 54 weeks of therapy. Remicade, which was generally well tolerated and produced minimal side effects, is the first monoclonal antibody to be evaluated for the treatment of RA.

TNF-alpha is a key inflammatory mediator, or cytokine, in rheumatoid arthritis and other autoimmune disorders. Overproduction of TNF-alpha leads to inflammation in these chronic conditions. It is believed that Remicade reduces inflammation in patients with rheumatoid arthritis by binding to and neutralizing TNF-alpha on the cell membrane and in the blood.

For more information: Centocor Inc., 200 Great Valley Pkwy., Malvern, PA 19355-1307. Tel: 610-651-6000. Fax: 610-651-6100.

Antisoma Gives Update on Theragyn Phase II Trial
At the 46th Annual Meeting of the US Society of Nuclear Medicine in Los Angeles, Antisoma plc (London), a biopharmaceutical company, presented an update on the progress of patients treated during the Phase II study of Theragyn, the monoclonal antibody treatment for ovarian cancer.

Twenty-one women who had no visible evidence of disease following surgery and chemotherapy were treated with Theragyn. Nineteen have now been followed for more than five years. Of these 19 patients, 16 (84%) were still alive five years after receiving treatment.

For more information: Agamemnon Epenetos, Chief Scientific Officer, Antisoma plc, West Africa House, Hanger Lane, Ealing, London W5 3QR, UK. Tel: +44 181-799-8200. Fax: +44 181-799-8201.

Osiris Begins Trial of Allogen in Cancer Patients
Osiris Therapeutics Inc. (Baltimore) has initiated a human clinical safety trial for Allogen in cancer patients receiving chemotherapy and hematopoietic stem cell transplantation for the treatment of high-risk hematological malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and non-Hodgkin's lymphoma.

Allogen is an infused, donor-derived (allogeneic) adult mesenchymal stem cell product that has been shown in preclinical studies to support engraftment without graft rejection or graft-versus-host disease (GVHD).

For more information: James S. Burns, President and CEO, Osiris Therapeutics Inc., 2001 Aliceanna St., Baltimore, MD 21231-3043. Tel: 410-522-5005. Fax: 410-522-6999.

Allelix's ALX-0600 Moves into Phase II Trial for SBS
Allelix Biopharmaceuticals Inc.'s (Mississauga, ON, Canada) gastrointestinal drug, ALX-0600, has moved into a pilot Phase II trial for short bowel syndrome (SBS), following a successful review by the FDA. This study will evaluate safety and efficacy, including bowel growth, nutrient absorption, and pharmacokinetics. Enrollment will begin in July, and the trial is scheduled to finish before the end of 1999.

ALX-0600 enhances the growth of the lining (epithelium) of the small intestine. The patented drug is Allelix's version of the natural peptide, Glucagon-like peptide 2 (GLP-2) but is more potent than the natural molecule and more resistant to breakdown by enzymes in the gut. ALX-0600 may aid in the treatment of several GI diseases, particularly those involving damage to the inner lining of the bowel.

For more information: Graham Strachan, President and CEO, Allelix Biopharmaceuticals Inc., 6850 Goreway Dr., Mississauga, ON L4V1V7, Canada. Tel: 905-677-0831. Fax: 905-677-9595.

NeoRx's Pretarget Technology Enables Higher Radiation Dosing
In clinical trials, NeoRx Corp.'s (Seattle) Pretarget technology permitted the safe administration of higher radiation doses to lymphoma patients than conventional radioimmunotherapy, and patients receiving these doses experienced substantial tumor regressions including complete responses in some cases. The maximum tolerated dose has not yet been reached.

The Pretarget technology employed involves first injecting a tumor-directed antibody carrying a receptor to the tumor, followed by a clearing step to remove the receptor from circulation. The radiation is then injected on a small molecule carrier that rapidly targets the receptor on the tumor, with most of the remaining radiation being quickly excreted from the body.

For more information: Paul Abrams, CEO, NeoRx Corp., 410 W. Harrison St., Seattle, WA 98119-4007. Tel: 206-281-7001. Fax: 206-284-7112.

Ariad Completes Phase I Trials of AP1903 Dimerizer Drug
Ariad Pharmaceuticals Inc. (Cambridge, MA) has completed a Phase I clinical trial of their first Dimerizer Drug (AP1903) for treatment of graft-versus-host disease (GVHD). The Argent (Ariad Regulated Gene Expression Technology) product was used to treat GVHD in patients undergoing allogeneic bone marrow transplants by eliminating transplanted T cells that are attacking normal tissue and causing GVHD. Phase II studies should be initiated later this year.

Conventional protein therapeutics require administration of a protein to the patient by frequent injections. This can be inconvenient and uncomfortable and can result in circulating protein levels that fluctuate well above and below the optimal therapeutic dose, thereby limiting both the safety and efficacy of such therapies. In Argent products, precisely controlled levels of a specific therapeutic protein can be produced in response to a small-molecule Dimerizer Drug delivered as a pill.

For more information: Harvey J. Berger, CEO, Ariad Pharmaceuticals Inc., 26 Landsdowne St., Cambridge, MA 02139-4234. Tel: 617-494-0400. Fax: 617-494-8144.

Vioxx/Celebrex Comparison Results Refuted
G. D. Searle & Co. (Skokie, IL) and Pfizer Inc. (New York) have refuted claims by Merck & Co. (Whitehouse Station, NJ) about the pain-relieving benefits of Merck's COX-2 inhibitor, because conclusions were drawn from a poorly designed study. Searle and Pfizer, who co-promote Celebrex (celecoxib capsules), asserted that Merck's conclusions were erroneous because the company used inequivalent doses when comparing Celebrex with Merck's Vioxx (rofecoxib).

The Merck study compared the lowest recommended dose for Celebrex (200 mg per day) with the highest possible dose of Vioxx (50 mg per day). Searle and Pfizer believe these data are misleading because the maximum recommended daily dose of Celebrex in the US is 400 mg.

For more information: Philip Needleman, Co-President, G. D. Searle & Co., 5200 Old Orchard Rd., Skokie, IL 60077. Tel: 847-982-7000. Fax: 847-470-1480.