Clinical Trials Roundup—Week of 5/17

Lane Labs, NCI Sponsor Trial of BeneFin for Breast, Colon Cancer
Lane Labs USA Inc. (Allendale, NJ) and the National Cancer Institute (NCI) have agreed to sponsor a Phase III Clinical Trial of BeneFin shark cartilage through the North Central Cancer Treatment Group. The study, which will begin later this year, will enroll approximately 600 patients with advanced breast and/or colon cancer. Phase II clinical trials using BeneFin on late-stage brain, breast, and prostate cancer patients are currently in progress.

For more information: Andrew Lane, President, Lane Labs USA Inc., 110 Commerce Dr., Allendale, NJ 07401. Tel: 800-526-3005 or 201-236-9090. Fax: 201-236-9091.

XOMA Closes Enrollment in Neuprex Phase III Trial
XOMA Ltd. (Berkeley, CA) has concluded patient enrollment in the Phase III pivotal trial of its Neuprex product in patients with severe pediatric meningococcemia, a deadly bacterial infection that primarily affects children. The decision to close enrollment was made after consultation with the FDA. This double-blinded, placebo-controlled trial has enrolled nearly 400 patients at US and UK hospitals, making it the largest controlled therapeutic clinical trial ever conducted in this disease.

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

Introgen Reports Promising Results of Adenoviral-p35 Trial
Introgen Therapeutics Inc. (Austin, TX) has reported results from a Phase I adenoviral-p53 gene therapy trial treating patients with prostate cancer. Introgen reported promising safety and early clinical activity data in prostate cancer for its lead product, Adenoviral-p53. The data suggest that the p53 therapy may provide an alternative treatment to debilitating surgery and toxic radiotherapy treatments.

In addition, the company announced that the p53 gene is well-tolerated and shows anti-tumor activity in patients with incurable head and neck cancer who have relapsed after standard therapy, according to results of a Phase II clinical study. 170 patients were treated in three coordinated studies, which evaluated various dosage levels and schedules for safety, tolerance, and efficacy.

For more information: James 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.

Evacet Studies Show Reduced Cardiotoxicity, Increased Effectiveness
In a recent head-to-head Phase III trial, Evacet (TLC D-99), The Liposome Co.'s (Princeton, NJ) new investigational liposome-encapsulated doxorubicin, showed a statistically significant reduction in cardiotoxicity (including congestive heart failure) when used to treat women with metastatic breast cancer, as compared to the widely used conventional formulation of doxorubicin. Gastrointestinal toxicity also was reduced in the Evacet group.

Another trial showed that Evacet was statistically more effective than epirubicin, another drug in the same class. The patients receiving Evacet showed a significantly prolonged time to disease progression, duration of response, and time to treatment failure than the epirubicin-treated patients. In both studies, patients also received the anticancer drug cyclophosphamide (CPA).

For more information: The Liposome Co. Inc., One Research Way, Princeton Forrestal Center, Princeton, NJ 08540. Tel: 609-452-7060. Fax: 609-452-1890.

IntraDose More Effective than Intravenous Chemotherapy
Clinical study results indicate that IntraDose (cisplatin/epinephrine) Injectable Gel, a localized chemotherapy product being developed by Matrix Pharmaceutical Inc. (Freemont, CA), may reduce the size of solid tumors, improve quality of life, and produce fewer traditional chemotherapy-related side effects than intravenous chemotherapy. IntraDose delivers cisplatin, a common anticancer drug, directly into tumors.

IntraDose is a cisplatin, epinephrine, and collagen gel that is injected directly into the tumor, where it is retained for several hours. IntraDose delivers much higher concentrations of cisplatin into the tumor than can be administered intravenously. Because IntraDose limits the exposure of normal, healthy tissue to the cytotoxic agent, it can also diminish the debilitating effects common to systemic chemotherapy, such as nausea, hair loss, and anemia.

For more information: Michael Casey, President and CEO, Matrix Pharmaceuticals Inc., 34700 Campus Dr., Fremont, CA 94555. Tel: 510-742-9900. Fax: 510-742-8510.

Immunex Begins Phase II Trial of CD40L for Renal Cell Carcinoma
Immunex Corporation (Seattle) has launched a Phase II trial of the investigational agent CD40 Ligand (CD40L) in the most common form of kidney cancer, renal cell carcinoma. The company is continuing the development of CD40L based on positive results of a multi-dose Phase I trial of the drug in advanced cancer patients.

CD40L is a protein primarily expressed on the surface of activated CD4+ T cells. Its receptor, CD40, is expressed on B cells—antigen-presenting cells such as dendritic cells, macrophages, and on some other normal and tumor cells. Pre-clinical research has shown that CD40L can stop tumor growth and actually kill many tumor cell types, either by activating the immune system against the tumor, or by signaling the tumor to stop growing or self-destruct.

For more information: Ann Hayes, Senior VP of Medical Development, Immunex Corp., 51 University St., Seattle, WA 98101. Tel: 206-587-0430. Fax: 206-587-0606.

Genta's G3139 Effective in Phase I-II Trials
Genta Inc. (Lexington, MA) announced the results of clinical studies with Genta's lead cancer drug in development, G3139. The Phase I-II clinical trials of G3139 demonstrated patient tolerance, biologic activity, and clinical shrinkage of drug-resistant cancers, including non-Hodgkin's lymphoma, prostate cancer, kidney cancer, and advanced malignant melanoma.

G3139 was designed to reduce the BCL-2 protein level in cancer through an antisense mechanism that specifically targets the BCL-2 gene product. In many human cancers, the BCL-2 protein is believed to be a major factor in inhibiting apoptosis, or programmed cell death, and in contributing to resistance by those cancers to treatment with anticancer drugs.

For more information: Kenneth G. Kasses, President and CEO, Genta Inc., 3550 General Atomics Ct., San Diego, CA 92121. Tel: 619-455-2700.

Titan Reports Promising Preliminary Results for Cancer Vaccines
Titan Pharmaceuticals Inc. (South San Francisco, CA) reported on the results of ongoing studies with two of its therapeutic cancer vaccines, TriGem and TriAb. In an ongoing Phase II clinical study of TriGem in patients with metastatic melanoma, 40 of 47 patients generated strong, anti- cancer immune responses following administration of TriGem. TriGem is a novel monoclonal antibody vaccine that mimics the GD2 antigen, present on melanoma, small cell lung cancer, and other malignancies.

In an ongoing Phase II clinical study with TriAb, consistent, vigorous immune responses against the tumor antigen HMFG were generated in metastatic breast cancer patients despite the decrease in immune function seen after autologous stem cell therapy. None of the treated patients experienced any significant adverse effects from treatment with the vaccine.

For more information: Louis R. Bucalo, President and CEO, Titan Pharmaceuticals Inc., 400 Oyster Point Blvd., Ste. 505, South San Francisco, CA 94080-1921. Tel: 650-244-4990. Fax: 650-244-4956.

Cell Pathways Reports on Clinical Trials of Exisulind
Cell Pathways Inc. (Horsham, PA) announced results demonstrating synergy between the company's lead investigational drug, exisulind, and chemopreventive and chemotherapeutic drugs in both cell culture and animal models of lung cancer. The company also reported that selective apoptotic anti-neoplastic drugs (Saands), such as exisulind and Cell Pathway's CP461, induce apoptosis in leukemia and myeloma cell lines. Further, preclinical studies demonstrated the ability of exisulind and an additional Cell Pathway's Saand, CP248, to trigger apoptosis in both androgen-sensitive and androgen-insensitive prostate cancer cells.

By specifically inhibiting the action of the novel cGMP-PDE, exisulind and other Saands enable abnormal cells to process an apoptotic signal and commit suicide without affecting normal cells.

For more information: Rifat Pamukcu, Senior VP of Research and Development, Cell Pathways Inc., 702 Electronic Dr., Horsham, PA 19044. Tel: 215-706-3800. Fax: 215-706-3801.

Antigenics Completes Phase I-II Renal Cell Carcinoma Trial, Launches Phase II
Antigenics (New York) announced the results of its Phase I-II renal cell carcinoma clinical trial with the company's lead cancer product, HSPPC-96, an autologous protein that is prepared from individual patient's tumors. The purpose of the 42 patient trial was to determine feasibility and safety of the vaccine and to measure tumor-specific immune response. No vaccine-related adverse affects were reported. Based on these results, Antigenics has begun an accelerated Phase II trial in renal cell carcinoma.

In a separate trial for pancreatic cancer, HSPPC-96 stimulated a tumor-specific immune response in approximately half of the patients tested.

For more information: Antigenics, 630 Fifth Avenue, New York, NY 10111. Tel: 212-332-4774. Fax: 212-332-4778.

Immune Modulation Technology Controls Antiviral Immune Response to Hepatitis B
Enzo Biochem (Farmingdale, NY) reports encouraging results from a recent laboratory study of their new approach to treat undesirable immune responses that can lead to serious liver damage among patients suffering from chronic hepatitis B virus. Using immune modulation technology developed by Enzo, oral administration of specific hepatitis B proteins was successful in controlling the antiviral immune response to hepatitis B. Enzo said it plans to begin human clinical trials using its immune modulation technology.

Hepatitis B virus (HBV) is a non-cytopathic virus, which means the virus itself does not destroy cells. Rather, it is the body's immune response to the virus that mediates the hepatocellular injury and liver damage. Enzo's approach could be used to attenuate the immune response directed against hepatocytes and thus could be used to turn chronic active hepatitis B patients into asymptomatic HBV carriers.

For more information: Elazar Rabbani, CEO, Enzo Biochem Inc., 60 Executive Blvd., Farmingdale, NY 11735. Tel: 516-755-5500. Fax: 516-755-5561.

Triangle Completes Phase I/II Study of Coviracil
Triangle Pharmaceuticals Inc. (Durham, NC) has completed Phase I/II dose-escalation study of the safety, tolerance, pharmacokinetics, and anti-hepatitis B (HBV) activity of Coviracil (emtricitabine), an antiviral nucleoside analogue with potent activity against HIV in vivo. Preclinical results have previously shown that Coviracil also possesses potent in vitro activity against HBV.

Forty-four HBV-infected patients were divided into 5 groups and administered Coviracil at doses of 25, 50, 100, 200, or 300mg once a day. After 56 days of treatment, HBV DNA levels decreased in all patients. Using PCR assay, the median reduction in viral load after 56 days of treatment ranged from 2.0 log10 at 25mg once a day, to 4.3 log10 at 200mg once a day.

For more information: Franck Rousseau, VP of Medical Affairs and Chief Medical Officer, Triangle Pharmaceuticals Inc., 4 University Place, 4611 University Dr., Durham, NC 27707. Tel: 919-493-5980. Fax: 919-493-5925.

Enrollment for Beta LT Clinical Trial Over 30% Complete
LifeTime Pharmaceuticals (Silver Spring, MD), Dovetail Technologies Inc. (College Park, MD), and the Jewish General Hospital (Montreal) announce that the Phase I/II clinical trial evaluating the anti-cancer and immune system boosting properties of Beta LT (also known as Betathine) in patients having low grade B-cell lymphoma has enrolled over one third (5 of 14) of the initially targeted population. The full target dose was given to all enrolled patients without any adverse events or any side effects being reported by either patients or their physicians. The first patients treated have been receiving Beta LT for 9 weeks.

Beta LT is a small disulfide drug produced by organic chemistry that is designed to cause a coordinated bone marrow, lymphocyte and monocyte response without toxic side effects.

For more information: Judith Evans, Executive VP, Dovetail Technologies Inc., Building 337, Paint Branch Dr., College Park, MD 20742. Tel: 301-405-0608. Fax: 301-405-9187.

PDL Presents Results from Phase I, I/II Trials of Smart Antibody
Protein Design Labs Inc. (Mountain View, CA) presented Phase I and preliminary Phase I/II clinical results using the Smart (humanized) Anti-CD3 Antibody (also known as HuM291) in kidney transplantation. In the Phase I single-escalating-dose trial, a dose dependent depletion of T lymphocytes from the blood was seen at the three highest doses tested (0.0015–0.015 mg/kg). In the Phase I/II multidose trial, results to date indicate that the degree and duration of T cell depletion increased with higher doses.

The Smart Anti-CD3 Antibody targets the CD3 antigen on T lymphocytes, a cell type involved in graft rejection. It is humanized and has been modified using proprietary PDL technology to avoid the potentially serious cytokine release syndrome associated with the mouse antibody.

For more information: Protein Design Labs Inc., 2375 Garcia Ave., Mountain View, CA 94043. Tel: 650-903-3700. Fax: 650-903-3730.

Rituximab Effective in Treating Non-Hodgkin's Lymphoma
Preliminary results of a pilot and a Phase II study using Rituximab to treat non-Hodgkin's lymphoma (NHL) show Rituximab to be effective when combined with Fludarabine (a chemotherapy) and when used alone dosed. In the pilot trial, Rituximab, when used alone to treat relapsed or refractory, low-grade B-cell NHL patients, showed a 48% response rate. Phase II study results suggests that dosing of Rituximab over a longer period of time may be associated with higher response rates and longer duration of response.

Rituximab, marketed by Genentech Inc. (South San Francisco, CA) and by IDEC Pharmaceuticals (San Diego) as Rituxan, has been approved by the FDA for the treatment of low-grade or follicular CD20-positive B-cell NHL.

For more information: Genentech Inc., One DNA Way, South San Francisco, CA 94080-4990. Tel: 650-225-1000. Fax: 650-225-6000.

Genetronics' EPT System Enhances Delivery of Chemotherapy
Genetronics Biomedical Ltd. (San Diego) announced interim data and results from Phase II clinical trials in the US and Canada for the treatment of squamous cell carcinoma of the head and neck. The trials were designed to evaluate the use of the company's proprietary Electroporation Therapy (EPT) system, which incorporates intra-tumoral injection of a chemotherapeutic agent combined with a pulsed electric field. Genetronics also announced preliminary data and results from a similar study conducted in Europe.

In each study, the patients' lesions were treated with bleomycin and the EPT system. Clinical response was determined by either complete disappearance of the tumor or reduction in size by at least 50%. For the 33 patients in the Phase II trials, a clinical response was achieved in 64% of the 42 tumors. In the twelve-patient European study, preliminary results show that 12 of the 19 tumors treated (63%) demonstrated a clinical response.

For more information: Paul Goldfarb, Medical Director, Genetronics Biomedical Ltd., 11199 Sorrento Valley Rd., San Diego, CA 92121-1334. Tel: 619-597-6006. Fax: 619-597-0119.

Rapamycin Curbs Organ Rejection in Trial
A recent study compared cyclosporine, the most popular anti-organ-rejection drug, with Wyeth-Ayerst's (Wayne, PA) experimental drug rapamycin as a treatment for "chronic" rejection—a progressive deterioration of the transplant that eventually strikes most patients who survive the first few months after surgery.

Researchers used a surgical technique that produces a form of chronic rejection in monkeys. Into each of 18 monkeys they grafted a segment of aorta taken from unrelated monkeys. They then tracked the course of rejection over 105 days. By the end of the experiment, the grafts from the monkeys treated with rapamycin had about 40% less scarring than the untreated monkeys and about 20% less than the monkeys treated with cyclosporine.

For more information: Wyeth-Ayerst Laboratories, 555 E. Lancaster Ave., Wayne, PA 19087-5109. Tel: 610- 688-4400.

Isis Antisense Cancer Drugs in Phase I, Phase II Trials
Isis Pharmaceuticals (Carlsbad, CA) presented data on three antisense cancer drugs in Phase I clinical trials: ISIS 3521(targeted to PKC-alpha) in combination with standard cytotoxic agents, ISIS 5132 (targeted to C-raf Kinase), and ISIS 2503 (targeted to Ha-ras). The data from the trials demonstrated that these drugs stimulated positive responses, and are well-tolerated, with only minimal side effects.

The three drugs are also in Phase II trials as single-agent therapy in patients with solid tumors.

For more information: Stanley Crooke, CEO, Isis Pharmaceuticals Inc., 2292 Faraday Ave., Carlsbad, CA 92008. Tel: 760-931-9200. Fax: 760-931-9639.

North American's Group C Meningococcal Conjugate Outperforms Competition
In a comparative infant clinical trial held in the UK, North American Vaccine's (Columbia, MD) group C meningococcal conjugate vaccine elicited significantly higher total antibody levels in infants after the first dose, compared to vaccines manufactured by Chiron Corp. and American Home Products' Wyeth-Lederle Vaccine Division. The study also demonstrated that the company's vaccine elicited antibody levels high enough to be protective in infants after just two doses of the three-dose immunization schedule.

The results from this infant trial are consistent with the data from a previous clinical study in toddlers in which the company's vaccine elicited significantly higher bactericidal antibodies than vaccines manufactured by the competitors.

For further information contact: Randal Chase, President and CEO, North American Vaccine Inc., 10150 Old Columbia Rd., Columbia, MD 21046. Tel: 410-309-7100.

Study Confirms Safety, Lack of Side Effects for Declopramide
OxiGene Inc. (Boston) announced interim results for its two dose-ranging Phase I clinical trials of Declopramide in patients with advanced stage cancer. Both studies demonstrated a favorable safety profile, and indicated a lack of central nervous system (CSN) side effects. Based on these results, the study was recently amended to continue dose escalation beyond the highest dose set in the initial protocol.

Declopramide, an oral formulation, is a DNA repair inhibitor based on the N-substituted benzamide class of compounds. Declopramide acts by enhancing conventional chemotherapy through the inhibition of DNA repair.

For more information: Bjorn Nordenvall, President and CEO, OxiGene Inc., One Copley Place, Ste. 602, Boston, MA 02116. Tel: 617-536-9500. Fax: 617-536-4700.

Clozapine Comparable to Clozaril in Treatment of Schizophrenia
A recent retrospective study has substantiated that a generic form of clozapine, developed by the Zenith Goldline Pharmaceuticals subsidiary of IVAX Corp. (Miami), and Novartis' (Basle, Switzerland) branded Clozaril can be used interchangeably for the treatment of severe schizophrenia. The study determined that clozapine patients can be maintained safely and successfully on the generic product and that the frequency of adverse events associated with clozapine usage was consistent with that of the branded drug.

Clozapine is the only AB-rated generic version of Clozaril on the market.

For more information: IVAX Corp., 4400 Biscayne Blvd., Miami, FL 33137-3227. Tel: 305-575-6000. Fax: 305-575-6298.

Oral Insulin Formulation Comparable to Injected Form
Generex Biotechnology Corp. (Toronto) today released additional data on tests of the company's oral insulin formulation recently conducted in Toronto and Princeton, NJ. The tests demonstrated that the company's bucally-administered insulin formulation (Oralin in Canada, and Oralgen in the US) controls post-prandial hyperglycemia in a manner comparable to injected insulin. The preliminary test results involved administration of two different dosages of Oralin and a placebo to 11 type 2 diabetic patients.

For more information: Anna Gluskin, CEO Generex Biotechnology Corp., 33 Harbour Square, Suite 202, Toronto, Ontario Canada M5J 2G2. Tel: 416-364-2551. Fax: 416-364-9363. Email: info@generex.com.