Clinical Trials Roundup—Week of 5/31

Introgen's Adenoviral-p53 Therapy Enters Phase I Trial
Introgen Therapeutics Inc. (Austin, TX) has initiated a Phase I clinical trial utilizing Adenoviral-p53 gene therapy (RPR/INGN 201) in cancer patients with solid tumors. The trial will enroll patients with nonresectable solid tumors and for whom all prior therapies have failed. Patients will receive RPR/INGN 201 by intravenous infusion. This dose-escalating, in vivo gene therapy trial is designed to determine safety and feasibility of delivering a p53 therapeutic systemically.

Unlike current cancer treatments, RPR/INGN 201 has caused only minimal side effects in worldwide clinical trilas. Even after the administration of thousands of doses, the p53 therapeutic has not produced the side effects (such as severe vomiting, hair loss, or suppression of the immune system) typically associated with currently available cancer treatments.

For more information: James A. Merritt, VP of Clinical and Regulatory Affairs, Introgen Therapeutics Inc., 301 Congress Ave., Ste. 1850, Austin, TX 78701. Tel: 512-708-9310. Fax: 512-708-9311.

XOMA's rBPI21 May Provide Alternative Treatment for OME
A recent study by researchers at Leiden University Medical Center (LUMC; the Netherlands) demonstrates that rBPI21, a modified recombinant fragment of BPI, may be useful in treating otitis media with effusion (OME). BPI (bactericidal/permeability-increasing protein), a human protein with multiple anti-infective properties (including neutralizing endotoxin), is XOMA Ltd.'s (Berkeley, CA) primary drug development platform.

This was the first study to assess the efficacy of rBPI21 in an experimental model (in this case, a rat model) of OME. The study concludes that, given the effectiveness of rBPI21 in this model and the reported disadvantages of ventilation tubes, treatment with rBPI21 offers a promising new therapy for OME when antibiotics fail.

For more information: XOMA Ltd., 2910 Seventh St., Berkeley, CA 94710. Tel: 510-644-1170. Fax: 510-644-0539.

AVI Biopharma to Begin Phase II Trial of Avicine in Pancreatic Cancer Patients
AVI Biopharma Inc. (Portland, OR) will initiate a multicenter Phase II clinical trial of their therapeutic cancer vaccine, Avicine, in pancreatic cancer patients on June 15. The randomized trial, involving at least 50 patients, is designed to evaluate the safety and efficacy of Avicine alone, and the potential synergistic effects of Avicine in combination with Eli Lilly & Co.'s (Indianapolis) gemcitabine chemotherapy (Gemzar).

Avicine elicits a highly specific immune response to the human hormone and growth factor hCG, a cancer-associated oncofetal protein. Avicine is essentially a non-toxic immunotherapy and has been evaluated in five clinical trials. Early studies have provided evidence of objective tumor responses and apparent survival benefits in patients who have failed conventional therapy.

For more information: Denis R. Burger, President and CEO, AVI BioPharma Inc., One SW Columbia, Ste. 1105, Portland, OR 97201. Tel: 503-227-0554. Fax: 503-227-0751.

Alteon Completes Phase I Trials of ALT-711 Crosslink Breaker
ALT-711, Alteon Inc.'s (Ramsey, NJ) lead A.G.E crosslink breaker, has successfully completed initial Phase I human trials. The two placebo-controlled, double-blind, single and ascending dose studies enrolled 88 subjects, consisting of a younger group (aged 18 to 50 years) and an older group (aged 55 to 75 years). In addition, a 14-day multiple dosing trial was conducted in 16 older (65 to 75 years) subjects. Analyses of the clinical and safety data did not show any medically relevant events. Alteon is now planning further clinical development of the compound.

Aging is associated with a general increase in tissue stiffening, including the cardiovascular and bronchioalveolar systems and the skin, which is attributed, in part, to the crosslinking of long-lived proteins, such as collagen and elastin, initiated by the interaction of simple sugars. By "breaking" these crosslinks, ALT-711 may have an impact on late stages of aging-related and diabetic complications.

For more information: Kenneth I. Moch, President and CEO, Alteon Inc., 170 Williams Dr., Ramsey, NJ 07446. Tel: 201-934-5000. Fax: 201-934-8880.

CV Therapeutics Completes Dosing in Phase III Trial of Ranolazine
The last patient has completed treatment in CV Therapeutics Inc.'s (Palo Alto, CA) Phase III monotherapy trial for ranolazine, which CV is developing for the potential treatment of chronic stable angina. The company anticipates releasing preliminary results of this trial later this year.

The international Phase III trial was a randomized, double-blind, placebo controlled trial of ranolazine as monotherapy. A total of 175 patients completed treatment in this trial.

For more information: Louis G. Lange, CEO, CV Therapeutics Inc., 3172 Porter Dr., Palo Alto, CA 94304. Tel: 650-812-0585. Fax: 650-858-0390.

Novogen's P-081 Stimulates HDL Production in Trial
Novogen Ltd.'s (Sydney, Australia) P-081 has been found to stimulate the production of HDL cholesterol in post-menopausal women. In a blinded clinical trial, post-menopausal women took P-081 (50 mg/day) for six months. At the end of the treatment period, HDL cholesterol levels had increased by 28.6%, and the ratio of HDL cholesterol to LDL cholesterol had improved by 21%. When treatment was withdrawn and the patients given a placebo tablet, HDL-cholesterol levels returned almost to pre-treatment levels within two months.

P-081 is derived from an extract of red clover and contains plant estrogens known as isoflavones, a number of which have beneficial, though generally modest, effects on the body's production of cholesterol. The breakthrough with P-081 is the finding that a particular combination of four different isoflavones delivers a significant beneficial effect on cholesterol levels.

For more information: Alan Husband, Scientific Director, Novogen Ltd., 140 Wicks Rd., North Ryde, New South Wales 2113, Australia, Tel: +61-2-9878-0088. Fax: +61-2-9878-0055.

Vasomedical's EECP Reduces Frequency of Angina Episodes in Trial
Vasomedical Inc. (Westbury, NY) has completed a multicenter trial of Enhanced External Counterpulsation (EECP), its noninvasive outpatient treatment for coronary artery disease. One hundred thirty-nine patients with angina, who had documented coronary artery disease and positive exercise treadmill tests, were randomly assigned thirty-five hours of active or inactive counterpulsation over a four to seven week period.

Results of the randomized, placebo, controlled trial showed that EECP reduces the frequency of angina episodes and increases the length of time before exercise produces electrocardiograph changes indicating insufficient blood supply to the heart muscle in patients with symptomatic coronary artery disease.

For more information: Anthony E. Peacock, VP of Clinical Affairs, Vasomedical Inc., 180 Linden Ave., Westbury, NY 11590. Tel: 516-997-4600 ext. 120. Fax: 516-997-2299.

Dimethaid's Transdermal Carrier To Deliver Antifungal Medicine Into Toenails
Dimethaid Research (Markham, ON, Canada) has begun a pilot study to explore the effectiveness of its proprietary transdermal carrier in delivering antifungal medication into toenails, thereby allowing for improved treatment over existing therapies. The intent of the study is to measure the potential effectiveness of Dimethaid's patented carrier to transport an antifungal drug through the nail over a period of several weeks. This could permit the killing of the fungus infection even in the mature nail.

Dimethaid intends to initially use an indicator molecule in combination with its carrier and will then consider licensing opportunities for the clinical development of a new product.

For more information: Rebecca Keeler, President and CEO, Dimethaid Research, 1405 Denison St., Markham, ON, L3R 5V2, Canada. Tel: 905-415-1446. Fax: 905-415-1440.

Maxim Begins Phase II Trial of Maxamine for Treating Hepatitis C
Maxim Pharmaceuticals Inc. (San Diego) has commenced a Phase II clinical trial of Maxamine in the treatment of patients with chronic hepatitis C (HCV). The trial is designed to evaluate Maxamine Therapy, consisting in this trial of the combination of Maxamine and the cytokine interferon-alpha (IFN-(alpha)), in the treatment of chronic hepatitis C patients who have not previously received treatment with IFN-(alpha). The European-based study will evaluate the efficacy and safety of each of the four dosing regimens of Maxamine.

Maxamine Therapy combines the administration of Maxamine, which protects critical immune cells, with the administration of biotherapeutic agents such as the cytokine IFN-(alpha) designed to stimulate these immune cells. Maxim believes that Maxamine and these biotherapeutic agents are complementary and play synergistic roles in enhancing the immune system as combination therapies for the treatment of certain cancers and infectious diseases.

For more information: Larry G. Stambaugh, President and CEO, Maxim Pharmaceuticals Inc., 8899 University Center Ln., Suite 400, San Diego, CA 92122. Tel: 619-453-4040. Fax: 619-453-5005.

Celgene Completes Enrollment for Trial of d-MPH
Celgene Corp.'s (Warren, NJ) pivotal clinical trials designed to demonstrate efficacy of the company's version of a chirally pure version of Ritalin (d-methylphenidate, or d-MPH) are fully enrolled. The trials are being conducted by investigators at 18 centers throughout the US. Celgene anticipates completion of the trials this year.

Celgene is also developing a "pulse release" formulation of d-MPH. Initial clinical trials of the "pulse release" formulation are scheduled to commence later this year.

For more information: Sol Barer, President and COO, Celgene Corp., 7 Powder Horn Dr., Warren, NJ 07059. Tel: 732-271-1001. Fax: 732-271-4184.

Atrix Completes Phase I Trial of Atrigel Formulation
Atrix Laboratories Inc. (Fort Collins, CO) has successfully completed its Phase I human clinical study for delivery of leuprolide acetate in prostate cancer patients using its proprietary 30-day sustained released Atrigel formulation. Based on the positive results of the study, Atrix plans to begin clinical efficacy studies in patients with advanced prostate cancer in the second half of 1999.

The subcutaneous injections of the Atrigel formulation containing leuprolide acetate were well-tolerated with no unexpected adverse events.

For more information: John Urheim, CEO, Atrix Laboratories Inc., 2579 Midpoint Dr., Fort Collins, CO 80525. Tel: 970-482-5868. Fax: 970-482-9735.

Inflazyme Initiates Phase I Trials of IPL576,092 for Asthma
Inflazyme Pharmaceuticals Ltd. (Richmond, BC, Canada) has initiated Phase I clinical trials with its lead oral compound for the treatment of asthma: IPL576,092. The Phase I trial is a double-blind, placebo-controlled study in healthy male volunteers designed to assess the safety, tolerability, and pharmacokinetics of single ascending oral doses of IPL576,092. A follow-up study will evaluate the safety and tolerability of multiple doses of IPL576,092.

Inflazyme has demonstrated that IPL576,092 has a significant effect on mediators of inflammation in vitro and in standard pre-clinical in vivo studies of asthma when administered orally or by inhalation. These pre-clinical studies demonstrate that IPL576,092 may have the efficacy of inhaled glucocorticoids without the related side effects.

For more information: Ian McBeath, President and CEO, Inflazyme Pharmaceuticals Ltd., Suite 425, 5600 Parkwood Way, Richmond, BC, V6V 2M2, Canada. Tel: 604-279-8511.

FeRx Initiates Phase I/II Trials of MTC-DOX for Primary Liver Cancer
FeRx Inc. (San Diego) has initiated dose escalating Phase I/II clinical trials of its lead product, MTC-DOX, for treatment of patients with primary liver cancer. The trials are being conducted at the UCLA Medical Center (Los Angeles) and the UCSF Medical Center (San Francisco).

Magnetic Targeted Carriers (MTCs) are microparticles, composed of elemental iron and activated carbon, which serve as delivery vehicles for the site-specific targeting, retention, and sustained release of pharmaceuticals. In the current Phase I/II clinical trials, a widely used anti-cancer drug, Doxorubicin, is adsorbed to the MTCs for delivery to the tumor site.

For more information: Jacqueline Johnson, President and CEO, FeRx Inc., 4330 La Jolla Village Drive, Suite 250, San Diego, CA 92122. Tel: 619-677-7788. Fax: 619-677-9898.

Chiron Begins Study of Gene Therapy for Severe Hemophilia A
Chiron Corp. (Emeryville, CA) has initiated a Phase I study to evaluate the use of gene therapy for delivering Factor VIII (FVIII) to patients with severe hemophilia A. The trial is a multi-center, open-label, single-dose, interpatient dose-escalation study designed to assess safety and determine expression levels of FVIII. Participants will receive the FVIII gene therapy product by peripheral intravenous infusion, and will be monitored closely for one year following treatment.

Chiron's gene therapy product expressing human FVIII is designed to provide sustained FVIII blood levels sufficient to reduce or eliminate the incidence of bleeding episodes associated with the activities of daily living for these individuals. This is the first gene therapy for hemophilia in which the product is directly administered to the patient.

For more information: Lewis (Rusty) T. Williams, Chief Scientific Officer and President of R&D, Chiron Corp., 4560 Horton St., Emeryville, CA 94608-2916. Tel: 510-655-8730. Fax: 510-655-9910.