Clinical Trials Roundup—Week of 6/21
Levotech Completes Enrollment in Phase II/III Trial of Contraceptive Patch
Levotech Inc. (West Conshohocken, PA) has enrolled 87 female patients in a Phase II/III clinical trial of the efficacy of a seven-day contraceptive transdermal patch. The trial, which is being conducted in China, will evaluate the efficacy of three patch sizes (7.5 cm2, 10 cm2, and 12.5 cm2) over five menstrual cycles. In addition to hormone and drug level measurements, all subjects will receive ultrasound evaluation of follicular size and endometrial thickness.
According to Levotech President Te-Yen Chien, more than 1,000 woman-months of data on 157 women from previous trials have already demonstrated the ability of the Levotech transdermal patch system to deliver appropriate levels of progesterone and estrogen. Some of the women in these studies have used the patch for up to 18 months with a lower incidence of side effects than that reported with currently available products.
For more information: Hal Broderson, CEO, Levotech Inc., 100 Front St., Suite 1350, West Conshohocken, PA 19428. Tel: 610-940-0300. Fax: 610-940-0301. Email: hsbroderso@aol.com.
Novo Nordisk Completes Study of Prandin with Troglitazone for Type 2 Diabetes
Novo Nordisk Pharmaceuticals (Princeton, NJ) has released clinical data using the oral antidiabetic drug (OAD) Prandin (repaglinide) tablets in combination with troglitazone tablets in patients with type 2 diabetes. Combination therapy proved more effective for reducing HbA(1c) levels than either Prandin or troglitazone alone. Mean HbA(1c) levels decreased in combination therapy (8.7 to 7.0%) and Prandin-treated (8.8 to 8.0%) groups, while a smaller decrease was observed among troglitazone-treated (8.5 to 8.1 %) subjects. The frequency of hypoglycemia (percentage with at least one event) reported was 5%, 6%, and 3% in the combination, Prandin, and troglitazone groups, respectively.
Prandin is in a unique class of insulin secretagogues called meglitinides and is characterized by a rapid and short-acting stimulation of insulin secretion in response to glucose. Troglitazone belongs to the thiazolidinedione class of OAD agents, which exert their effect through increasing insulin sensitivity in peripheral tissue. Prandin is not indicated for use in combination with troglitazone tablets.
For more information: Novo Nordisk Pharmaceuticals Inc., 100 Overlook Center, Princeton NJ 08540. Tel: 800-727-6500.
AC-6 Gene Improves Heart Function in Preclinical Study
A new preclinical study found that AC-6 gene may improve heart function in a preclinical animal model that closely resembles human congestive heart failure (CHF). Collateral Therapeutics (San Diego) exclusively licensed the technology used in this research from the University of California in 1997, and expects to begin clinical trials of Corgenic, an AC-6 gene therapy treatment for clinical CHF, early next year.
The study focuses on the effects of AC-6 as a therapeutic gene in the setting of experimental heart failure. Transgenic mice with cardiomyopathy were crossbred so that the AC-6 gene was present as a therapeutic gene in the background of cardiomyopathy. Treated animals showed a statistically significant improvement in heart function and in the heart's ability to respond to stress. Preliminary data indicated that treated animals had prolonged survival with 80% still alive after 12 months, compared to only 20% alive in the untreated group. Heart cells from treated mice had completely normal cAMP generation, an improvement compared to the untreated group.
For more information: Jack W. Reich, President and CEO, Collateral Therapeutics, 9360 Towne Centre Dr., San Diego, CA 92121. Tel: 619-824-6500. Fax: 619-824-6563.
Transgene Initiates Phase I Trial of Adenovirus-INF-Gamma for Malignant Melanoma
Transgene (Strasbourg, France) has initiated a new clinical trial using adenovirus-IFN-Gamma. This Phase I clinical trial is being conducted at the University of Rochester (Rochester, NY), in patients with advanced malignant melanoma, under a Transgene-sponsored Investigational New Drug (IND). The project is part of Transgene's efforts to enhance the human immune system's ability to reject cancer cells and thus provide an improved, less toxic alternative to chemotherapy and radiation in the treatment of advanced cancer.
The adenovirus-IFN-Gamma product is based on Transgene's adenovirus technology and is designed to produce interferon-Gamma, a natural cytokine that helps to stimulate the body's immune system. Studies in laboratory animals have indicated the potential value of this compound in stimulating the immune system and enhancing the response against cancer, both alone and in combination with other forms of immunotherapy.
For more information: Bernard Gilly, President and CEO, Transgene, 11, rue de Molsheim, 67082 Strasbourg Cedex, France. Tel: +33-3-88-27-91-00. Fax: +33-3-88-27-91-11.
EPIX, Malinckrodt Initiate Trial of Intravascular MRI Contrast Agent
EPIX Medical Inc. (Cambridge, MA) and Mallinckrodt Inc. (St. Louis) have started a Phase III efficacy trial for AngioMARK (MS-325), the companies' intravascular MRI contrast agent in development for the detection of aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease or abdominal aortic aneurysm. The multi-center is designed to compare the diagnostic accuracy of AngioMARK-enhanced MRI with that of X-ray angiography, the current standard for diagnosing vascular disease.
Highly-invasive X-ray angiography is currently the reference standard for the diagnosis of non- coronary vascular disease. The companies believe that AngioMARK will provide radiologists with a non-invasive means of visualizing the peripheral vasculature early in the patient work-up, potentially aiding clinicians in making definitive diagnoses and planning surgery. The 600-patient Phase III study is being conducted at over 50 sites in the US, Canada, and Europe.
For more information: Michael D. Webb, President and CEO, EPIX Medical Inc., 71 Rogers St., Cambridge, MA 02142. Tel: 617-499-1400. Fax: 617-499-1414.
Avant to Begin Enrollment in Phase I Trial of Atherosclerosis Vaccine
Avant Immunotherapeutics Inc. (Needham, MA) has received approval to begin enrollment in its Phase I clinical trial of CETi-1, AVANT's investigational vaccine aimed at preventing or treating atherosclerosis by raising serum levels of HDL (high-density lipoprotein) cholesterol. The Phase I study is a double-blind, ascending-dose trial to assess the safety and immunogenicity of CETi-1.
CETi-1 is an immunotherapeutic designed to raise serum HDL cholesterol levels by blocking the transfer of cholesterol from HDL to LDL. HDL acts to protect against atherosclerosis while LDL acts to promote atherosclerosis. CETi-1 induces antibodies against a portion of the serum protein responsible for this transfer, cholesteryl ester transfer protein (CETP).
For more information: Una S. Ryan, CEO, Avant Immunotherapeutics Inc., 119 Fourth Ave., Needham, MA 02194-2725. Tel: 781-433-0771. Fax: 781-433-0262.
BioCryst Initiates Phase II Trial of Oral Influenza Inhibitor, Receives Milestone Payment
BioCryst Pharmaceuticals Inc. (Birmingham, AL) has received a $2 million milestone payment from Ortho-McNeil Pharmaceutical Inc. in connection with the initiation of Phase II clinical testing in the US of an oral influenza neuraminidase inhibitor designed to treat and prevent viral influenza.
The milestone payment is in conjunction with BioCryst's September 1998 worldwide license agreement with the R.W. Johnson Pharmaceutical Research Institute (PRI) and Ortho-McNeil, both Johnson & Johnson (New Brunswick, NJ) companies located in Raritan, NJ. PRI is responsible for the research, development, and expenses of BioCryst's oral influenza inhibitor. Ortho-McNeil will market products cleared for marketing in the US.
For more information: Charles E. Bugg, CEO, BioCryst Pharmaceuticals Inc., 2190 Parkway Lake Dr., Ste. B, Birmingham, AL 35244. Tel: 205-444-4600. Fax: 205-444-4640.
Trimeris Begins Phase II Trial of T-20 with Other Anti-HIV Drugs
Trimeris Inc. (Durham, NC) has commenced patient selection and dosing in its T20-206 Phase II clinical trial for T-20. The trial will assess the antiviral activity and long-term safety of T-20 when used in combination with other anti-HIV drugs.
T20-206 will evaluate four groups of patients over a one-year period with analyses at 16 weeks and 48 weeks. Three different doses of T-20 will be combined with a background regimen of amprenavir, efavirenz, ritonavir, and abacavir. The control group will receive the background regimen without T-20. At entry, all enrolled patients will have prior exposure to nucleoside reverse transcriptase inhibitors and protease inhibitors, but no prior exposure to non-nucleoside reverse transcriptase inhibitors.
For more information: Dani Bolognesi, CEO and Chief Scientific Officer, Trimeris Inc., 4727 University Dr., Ste. 100, Durham, NC 27707. Tel: 919-419-6050. Fax: 919-419-1816.
Bioenvision Completes Successful Phase I Trial of Immunosuppressive Agent
Bioenvision Inc. (London), a biopharmaceutical company, has completed its Phase I clinical trial of clofarabine. Results of the trial, conducted at the MD Anderson Cancer Center in Houston, showed that the drug is a potent immunosuppressive agent with no unexpected side-effects.
Phase II protocols to use clofarabine in leukemia, lymphoma, and several solid tumors are now being submitted. Researchers at the MD Anderson Cancer Center have also shown that clofarabine, like some other drugs in the class, will prevent DNA repair and therefore could be used in combination with DNA-damaging chemotherapeutic drugs. This could greatly extend the role of clofarabine beyond the treatment of hematological cancers and into the realm of solid tumors.
For more information: Christopher Wood, President and CEO, Bioenvision Inc. Tel +11-44-171-839-7570.
SafeScience Completes Phase I/II Study of Anti-Cancer Compound
SafeScience Inc. (Boston) has completed a Phase I/II clinical study of the anti-cancer compound, GBC-590. The results show that the compound is well tolerated and effective in reducing or stabilizing PSA (prostate specific antigen) levels in 18 out of 22 relapsing prostate cancer patients that are resistant to standard therapy. As a result, the company will commence Phase II studies for prostate cancer. SafeScience also will initiate a Phase I/II study for pancreatic carcinoma.
GBC-590 is a designed carbohydrate that represents a new class of drugs called "lectin inhibitors," which competitively bind to unique lectins on cancer cells and disrupt the metastatic process. To date, no dose-limiting GBC-590-related toxicities have been observed in clinical and preclinical trials, and GBC-590 has shown that it can shrink tumors as well as arrest tumor growth in preclinical studies on the PANC-1 human pancreatic cancer model and the LNCaP human prostate carcinoma model.
For more information: David Platt, CEO, SafeScience Inc., Park Square Bldg., 31 St. James Ave., Ste. 520, Boston, MA 02116. Tel: 617-621-3133. Fax: 617-621-0902.
Magainin Begins Phase II Testing of Angiogenesis Inhibitor
Magainin Pharmaceuticals Inc. (Plymouth Meeting, PA) has commenced a Phase II human clinical testing of squalamine, an angiogenesis inhibitor, for the treatment of patients with advanced non-small cell lung cancer. The study will test the safety and efficacy of squalamine in combination with paclitaxel and carboplatin, the leading cytotoxic chemotherapeutic regimen for the treatment of advanced non-small cell lung cancer.
Squalamine is a small, synthetically produced molecule with a unique mechanism of action that blocks endothelial (blood vessel) cell activation, migration, and proliferation by multiple growth factors. Squalamine's intracellular blockade of multiple growth factors contrasts with many other angiogenesis inhibition programs. Preclinical studies have demonstrated that this multi-faceted approach may allow squalamine broad application across many cancer types.
For more information: Michael R. Dougherty, President and CEO, Magainin Pharmaceuticals Inc., 5110 Campus Dr., Plymouth Meeting, PA 19462. Tel: 610-941-4020. Fax: 610-941-5399.
Pharmacia & Upjohn's Tipranavir Effective Against Resistant Strains of HIV/AIDS
Results of an in vitro study suggest that tipranavir, the first in a new class of non-peptidic protease inhibitors (PIs), is active against strains of HIV that are highly resistant to all four protease inhibitors approved for use at the time of the study. In fact, 90% of the highly resistant isolates were completely sensitive to tipranavir. Tipranavir is currently in development by Pharmacia & Upjohn (Bridgewater, NJ).
Tipranavir is a non-peptidic HIV protease inhibitor currently in development by Pharmacia & Upjohn. Tipranavir is the first in this new class of non-peptidic protease inhibitors for the treatment of HIV/AIDS.
For more information: Fred Hassan, President and CEO, Pharmacia & Upjohn, 95 Corporate Dr., Bridgewater, NJ 08807-1265. Tel: 908-306-4400. Fax: 908-306-4433.
Selectus Starts Enrollment in Phase Iib Trial of Esprolol for Angina Pectoris
Selectus Pharmaceuticals Inc. (West Conshohocken, PA) is now enrolling patients into a double-blind, placebo-controlled Phase IIb clinical trial to evaluate the efficacy of esprolol for use in treating angina pectoris. Esprolol is a potent, rapidly acting, sublingual beta-blocker that attenuates heart rate and blood pressure increases during physical exertion. Selectus expects to complete the trial sometime this fall.
Esprolol is intended for patients intolerant to acute nitrate therapy (including patients taking Viagra), as an adjunct to nitrate therapy in patients with exertional pain, for patients who cannot tolerate chronic beta-blockers, and for outpatients who need acute treatment for supraventricular arrythmias including atrial fibrillation with rapid ventricular response.
For more information: Hal Broderson, CEO, Selectus Pharmaceuticals Inc., 100 Front St., Suite 1350, West Conshohocken, PA 19428. Tel: 610-940-0300. Fax: 610-940-0301. Email: hsbroderso@aol.com.