Clinical Trials Roundup—Week of 2/1

Lorus Subsidiary Tests Colon Cancer Compounds

NuChem Pharmaceuticals Inc., a Lorus Therapeutics subsidiary, has released positive preclinical data from a second study on the efficacy of certain novel anti-cancer compounds in a human tumor xenograft model commonly used for colon cancer.

In the confirmatory study, the efficacy of novel anti-cancer compounds was administered by subcutaneous and oral administration against currently available first- and second-line chemotherapeutic (cytotoxic) agents used for colon cancer—namely, 5-fluorouracil (5-FU) and irinotecan (CPT-11). The study also included treatments in which the cytotoxic agents, 5-Fu and CPT-11, were each combined with one of these novel compounds, NC384. The results showed that, relative to controls, NC384 significantly inhibited tumor growth after subcutaneous administration and after oral administration.

For more information: Lorus Therapeutics Inc., 1285 Morningside Avenue, Scarborough, Ontario, Canada, M1B 3W2. Telephone: 416-724-1509 (ext. 251). Fax: 416-724-1167.

Chronic Bronchitis Trial Begins Enrollment

A multi-center clinical trial is seeking volunteers with Chronic Bronchitis. The objective of the study is to test the safety and effectiveness of an investigational medication in the reduction of disease symptoms such as phlegm (sputum) and cough. Sponsored by a major international pharmaceutical company, the study is enrolling volunteers between the ages of 40 and 75 with a long-term history of smoking.

For more information: Respiratory Research Group, telephone: 1-800-92-TRIAL (1-800-928-7425).

HIV Protease Inhibitor Demonstrates Few Significant Side Effects

A preliminary study into Agenerase (amprenavir), a novel HIV protease inhibitor, has demonstrated it to be a potent drug with few significant side effects. Research highlights from the ongoing clinical trial include data from a large trial examining the activity of Agenerase in the treatment of HIV-infected children, results from a study examining the ability of Agenerase to lower virus levels in semen, and data from a detailed analysis of safety across clinical trials. Agenerase is awaiting market approval from regulatory authorities in the United States, Europe, Canada, and several other countries.

Agenerase was discovered at Vertex Pharmaceuticals and licensed to Glaxo Wellcome. Glaxo Wellcome will market Agenerase and Vertex Pharmaceuticals will co-promote the drug once approved.

For more information: Vertex Pharmaceuticals Inc., 130 Waverly St., Cambridge, MA 02139-4242, USA. Telephone: 617-577-6000. Fax: 617-577-6680.

MacroChem Initiates Benefin Trial

MacroChem Corp. has initiated Phase II clinical studies with Benefen, its topical formulation for the treatment of osteoarthritic pain. The Phase II double blind, placebo-controlled study compares the efficacy and safety of Benefen, a 5% ibuprofen topical gel containing MacroChem's patented transdermal enhancer SEPA, against a placebo.

For more information: MacroChem Corp., 110 Hartwell Avenue, Lexington, MA 02421-3134. Telephone: 781-862-4003. Fax: 781-862-4338.

Agouron Reports Plasma HIV RNA Levels Below Quantification

Agouron Pharmaceuticals Inc. has reported plasma HIV RNA levels below the level of quantification (<500 copies/mL, experimental Chiron bDNA assay) at a median follow-up of 60 weeks in a majority of trial patients. The patients had all failed treatment with Viracept (nelfinavir mesylate) in combination therapy and were treated with other protease inhibitors in combination therapy.

The new combination therapy consisted of 400mg Norvir (ritonavir) BID (twice daily) + 400mg Invirase (saquinavir hard gel) BID + 40mg Zerit BID + 150mg Epivir BID. All patients experienced an initial response to the new protease inhibitor-containing regimen, achieving HIV RNA levels below the limit of quantification. At the median follow-up interval of 60 weeks, 58% of patients maintained plasma HIV RNA levels below the limit of quantification in an intent-to-treat analysis.

For more information: Agouron Pharmaceuticals Inc., 10350 North Torrey Pines Road, La Jolla, CA 92037-1020, USA. Telephone: 800-501-AGPH. Fax: 619-622-3298.

Neurocrine Biosciences Begins Trials Of Sleep Drug

Neurocrine Biosciences has initiated Phase Ib clinical trials on NBI-34060, a GABA(A) Receptor Agonist, for insomnia. The objectives of the study are to assess safety, tolerability, pharmacokinetics and pharmacodynamics of multiple increasing doses of NBI-34060 in healthy volunteers.

NBI-34060 is a next generation non-benzodiazepine sedative hypnotic with receptor subtype selectivity, which is chemically distinct from the currently marketed benzodiazepines. The compound modulates specific GABA neurotransmitter receptor subtypes at the benzodiazepine site. NBI-34060 binds with high affinity to brain benzodiazepine receptors and shows sedative, anxiolytic, muscle-relaxant effects.

For more information: Neurocrine Biosciences, 10555 Science Center Drive, San Diego, CA 92121, USA. Telephone: 619-658-7600. Fax: 619-658-7602.

NeXstar Begins Phase I Trial Of Newest Drug Candidate

NeXstar Pharmaceuticals Inc. has initiated the first in a series of planned Phase I clinical trials for its newest drug candidate NX 211, a liposomal form of the investigational anticancer drug lurtotecan, a proprietary topoisomerase I inhibitor. The goal of this study is to test the safety of the product in patients with advanced-stage solid tumors.

For more information: NeXstar Pharmaceuticals, 2860 Wilderness Place, Boulder, CO 80301, USA. Telephone: 303-444-5893. Fax: 303-444-0672.

Abgenix Reports Phase II Trial Results Of GVHD Therapy

Abgenix Inc. has reported the results of a Phase II clinical trial of ABX-CBL in graft versus host disease (GVHD), an often fatal side effect of bone marrow transplants. ABX-CBL is a proprietary in-licensed mouse antibody that binds to the CBL antigen, which is over-expressed on activated immune cells, including T cells, B cells and natural killer cells.

After the trial successfully confirmed the safety and efficacy of ABX-CBL in treating GVHD, Abgenix now plans to initiate a pivotal Phase III clinical trial for ABX-CBL as soon as feasible after we have approval from the FDA to proceed.

For more information: Abgenix Inc., 7601 Dumbarton Circle, Fremont, CA 94555, USA. Telephone: 510-608-6500. Fax: 510-608-6511.

Palatin Begins Studies Of Second LeuTech Product Line

Palatin Technologies Inc. has entered Phase II studies on its second LeuTech product line, for the diagnosis of bone infections known as osteomyelitis. The first LeuTech product line, for diagnosing thoracic and abdominal infections such as equivocal appendicitis, is nearing the end of its Phase III clinical trials simultaneously.

Palatin's kit-packaged radiolabeled infection imaging system for the detection of osteomyelitis is the second indication of several planned for the LeuTech pipeline of products. The trial will consist of a 45 patient study at 4 sites.

For more information: Palatin Technologies Inc., 214 Carnegie Center, Ste. 100, Princeton, NJ 08540, USA. Telephone: 609-520-1911.

Virulizin Publication To Be Presented At AACR

The first peer-reviewed publication of the U.S. preclinical and clinical trials of Virulizin will be presented at the 1999 annual meeting of the American Association for Cancer Research (Philadelphia, PA; Apr. 10-14, 1999). Lorus Therapeutics submitted a scientific abstract, entitled "A Novel Immunotherapeutic Agent for Pancreatic Cancer: Results of Preclinical and Clinical Trials Using Virulizin" to the AACR in October 1998.

For more information: Lorus Therapeutics Inc., 1285 Morningside Avenue, Scarborough, Ontario, Canada, M1B 3W2. Telephone: 416-724-1509 (ext. 251). Fax: 416-724-1167.

Hughes Institute Scientists Discover Mast Cell Inhibitor

A novel inhibitor, developed by Hughes Institute scientists, has shown activity against allergy causing mast cell responses in clinical trials. Allergic reactions are mediated by the activation of mast cells through the crosslinking of high affinity receptors on the cell surface. The released mediators alone or in combination are responsible for the symptoms of allergic or asthmatic responses.

Hughes Institute scientists discovered that WHI-P180 is a potent inhibitor of mast cell functions in mice.

For more information: The Hughes Institute, 2665 Long Lake Road, Roseville, MN 55113, USA. Telephone: 651-697-9228.

Ixsys Initiates Trial Of Angiogenesis Inhibitor

Ixsys Inc. has initiated a Phase II trial of its angiogenesis inhibitor, Vitaxin, in Leiomyosarcoma patients. Vitaxin, the CDR-grafted version of the murine LM609 monoclonal antibody, is being developed by the company for the inhibition of angiogenesis associated with solid tumor growth.

The compound was created using Ixsys' Directed Evolution technology and represents the first of a new class of angiogenesis antagonists which recognize the integrin avb3, a receptor expressed on the surface of endothelial cells associated with new blood vessel formation or neovascularization.

For more information: Ixsys Inc., 3550 Dunhill Street, San Diego, CA 92121, USA. Telephone: 619-597-4990. Fax: 619-597-4950.

Abbott's Clot-Dissolving Drug Lessens Neurological Disability In Stroke Patients

A recently completed Phase III study, PROACT II, suggests Abbott Laboratories' investigational clot-dissolving drug can lessen the neurological disability associated with stroke. Forty percent of patients treated with r-ProUK (recombinant pro- urokinase), a clot-dissolving drug, had slight or no neurological disability 90 days after treatment, compared to 25% of control patients in the trial.

For more information: Abbott Laboratories, One Abbott Park Road, Abbott Park, IL 60064-3500, USA. Telephone: 847-937-6100. Fax: 847-937-1511.

Sustiva Achieves Greater Viral Suppression Than Crixivan In Trials

After 48 weeks of therapy, an anti-HIV therapy containing DuPont Pharmaceuticals' once-daily Sustiva (efavirenz) has achieved viral suppression in a greater percentage of patients than combinations including the protease inhibitor Crixivan (indinavir). Fewer patients in the arm containing Sustiva, AZT and 3TC dropped out due to adverse events than in the Crixivan/AZT/3TC arm under the trial. It is difficult to assess the relative efficacy of the treatment arms given the disproportionate discontinuations in an open-label study.

For more information: DuPont Pharmaceuticals, telephone: 1-800-4PHARMA (1-800-474-2762).

Discovery Labs Completes Trial Of Surfaxin In MAS Patients

Discovery Laboratories Inc. has successfully completed its Phase II clinical trial of Surfaxin in full-term infants with Meconium Aspiration Syndrome (MAS). Surfaxin, which contains a peptide mimic of the human surfactant protein B, was used to cleanse the lung (bronchoalveolar lavage or lung wash) and restore the surfactant inactivated by the meconium. This was an open label comparison of Surfaxin lavage versus standard of care conducted in 15 centers across the United States.

For more information: Discovery Laboratories Inc., 350 South Main Street, Suite 307, Doylestown, PA 18901. Telephone: 215-340-4699. Fax: 215-340-3940.