Business Wire - September 14, 2000
After 48 weeks of therapy, the combination of the optimal dosing regimen of Maxamine and IFN-(alpha) achieved a complete viral response in 61 percent of all patients, compared to the 29 percent or less response that is commonly observed in patients treated with IFN-(alpha) alone. The results are being presented at the Society of Biological Therapy conference in Berlin by the principal investigator in the study, Yoav Lurie, M.D., liver clinic director, Kaplan Medical Center, Israel.
"These are very strong 48-week results for the combination therapy using Maxamine with standard IFN-(alpha)," said Dr. Lurie. "This study had a significant percentage of patients with high viral loads and the genotype-1 virus, both of which are factors that would typically lead to a substantially lower response with either IFN-(alpha) alone or other existing treatments. These end-of-treatment results clearly suggest that Maxamine is providing a benefit not only to the overall study population but to these high-risk groups as well."
In addition to the favorable results in the overall study, response rates achieved for the higher-risk patients treated with the Maxamine/IFN-(alpha) combination were substantially better than those typically expected for treatment with IFN-(alpha) alone:
-- Despite the poor prognosis for successful treatment, 55 percent of the patients with the genotype-1 variant of the hepatitis C virus treated with the optimal dose regimen of Maxamine and IFN-(alpha) achieved a complete viral response at 48-weeks, compared to the less than 20 percent reported for IFN-(alpha) alone. Patients infected with the genotype-1 virus typically have the poorest response to treatment and comprise 70 percent of patients in the United States and Asia.
-- Patients with high viral levels, viral levels greater than 2 million copies per milliliter of blood, also typically have a poor response to treatment. However, 54 percent of the patients with more than 2 million copies per milliliter of blood treated with the optimal regimen of Maxamine and IFN-(alpha) achieved a complete viral response at 48-weeks, compared to the less than 20 percent reported for IFN-(alpha) alone.
"Based upon the clinical results achieved to date, we are currently planning two Phase III clinical trials in hepatitis C in collaboration with F. Hoffmann - La Roche using the combination of Maxamine with pegylated interferon and ribavirin," stated Kurt Gehlsen, Ph.D., Maxim vice president, development and chief technical officer. "We believe that Maxamine in combination with emerging new treatments based on the pegylated form of interferon may be synergistic and substantially improve outcomes for naive patients as well as for patients who are previously nonresponsive to therapy."
Phase II Study Design
The Phase II dose-ranging trial is designed to evaluate the combination of Maxamine and IFN-(alpha) in the treatment of chronic hepatitis C patients who had not been previously treated with IFN-(alpha). The primary goals of this study are to determine the most appropriate dosing regimen for Maxamine in the treatment of naive chronic hepatitis C patients, and to provide further evidence that Maxamine may benefit cytokines such as IFN-(alpha) in the treatment of this viral infection. The 129-patient trial is based in the United Kingdom, Belgium, Israel and Russia.
Patients were randomly assigned to one of four treatment groups, and each patient received Maxamine, in one of four dosing regimens, plus IFN-(alpha) at the standard dose of 3miu three times per week. Under the two lower-dose regimens, patients administered one dose of Maxamine each treatment day, and receive a total of either 3 mg or 5 mg of the drug per week of therapy. Under the two higher-dose regimens, patients administered two doses of Maxamine each treatment day, and receive a total of either 6 mg or 10 mg of the drug per week of therapy.
After 48 weeks of treatment, 61 percent of the patients treated with either of the two higher-dose, twice-per-day regimens of Maxamine achieved complete viral responses, compared to a 55 percent complete viral response for the patients treated with either of the two lower-dose, once-per-day regimens of Maxamine. The complete viral response for all patients in the study for all four treatment arms combined was 58 percent. Published reports suggest that only 29 percent or less of patients attain a complete viral response after 48 weeks of treatment with IFN-(alpha) alone.
The primary measures of efficacy in the study are a reduction in viral load and a normalization of liver function. A complete viral response is defined by virus levels that are below the limit of detection using a validated PCR-RNA technique. A complete biochemical response is defined as normalization of liver enzyme levels, measured by the liver enzyme ALT, a standard measure of liver function. Patients who responded during the first 12 weeks of treatment continued treatment through 48 weeks, with the 48-week, end-of-treatment, results summarized above. An additional evaluation will be made at the 72-week point (24 weeks after end of treatment).
Patients in the study were able to treat themselves at home with the Maxamine and IFN-(alpha) combination therapy. The 48-week results suggest that patient compliance and the safety profile of the therapy were consistent with the positive results shown in other ongoing and completed Maxamine trials.
Hepatitis C Overview
Hepatitis C is more easily transmitted than HIV and is now the leading blood-borne infection in the United States. The U.S. Center for Disease Control and Prevention estimates that over 4.5 million Americans are infected with the hepatitis C virus. The World Health Organization and other sources estimate that more than 200 million people are infected worldwide.
Hepatitis is a disease characterized by inflammation of the liver and, in many cases, permanent cirrhosis (scarring) of the liver tissues and mortality. The progress of disease from infection to significant liver damage can take 20 years or more. Some experts estimate that without substantial improvements in treatment, deaths from hepatitis C will surpass those from HIV. Hepatitis C is the leading cause of liver cancer and the primary reason for liver transplantation in many countries. The majority of patients do not effectively respond to existing therapies or to therapies known by us to be under development.
In addition to the Phase II dose-ranging study, the company also has a clinical study underway to evaluate the safety of triple-drug therapy incorporating Maxamine in combination with IFN-(alpha) and the anti-viral drug ribavirin in hepatitis C patients who were nonresponsive to prior therapy. The company expects to conduct its Phase III studies under the umbrella of a comprehensive development collaboration with F. Hoffmann - La Roche for the clinical development and approval of Maxamine in combination with Pegasys(R), Roche's pegylated interferon-alpha agent. The collaboration program will include two Phase III trials of the Maxamine and Pegasys combination for the treatment of hepatitis C, one in naive patients, and one in patients who were nonresponsive to prior therapy.
Maxamine Overview
Treatment with Maxamine is based upon the discovery of a universal mechanism that suppresses the capacity of the immune system to detect and destroy tumor cells or virally infected cells in many patients with cancer and chronic infectious diseases. Maxamine is designed to reverse this immune suppression, thereby enhancing the effectiveness of immunotherapy, a class of therapies that employ the body's immune system to fight cancer and certain infectious diseases. Maxamine protects critical immune cells and is administered in combination with cytokines such as interleukin-2 (IL-2) and IFN-(alpha), a class of proteins that stimulate these same immune cells. More than 1,200 patients have been treated in the company's completed and ongoing clinical trials in advanced malignant melanoma, acute myelogenous leukemia, hepatitis C and renal cell carcinoma. Maxamine is an investigational drug and has not been approved by the FDA or any international regulatory agency. However, clinical trial results to date suggest that Maxamine Therapy, the administration of Maxamine in combination with cytokines, is a safe, at-home treatment that may improve patient survival.
Maxim Pharmaceuticals is a late-stage biopharmaceutical company developing advanced drugs and therapies for cancer, infectious diseases, degenerative diseases and topical disorders. In July 2000 the company submitted a New Drug Application (NDA) to the FDA seeking approval to market Maxamine in the United States as an adjuvant to IL-2 for the treatment of advanced metastatic melanoma. In September 2000 the FDA informed the company that the NDA had been accepted for review as filed, and that the NDA had been granted priority review status and would be reviewed under the accelerated approval statutes. In addition, Maxamine is also currently being tested in two additional Phase III cancer clinical trials in 12 countries for malignant melanoma and acute myelogenous leukemia. Phase II trials of Maxamine are also underway for the treatment of hepatitis C and advanced renal cell carcinoma.
The company has also developed product candidates based on its MaxDerm(TM) technology that are designed for the treatment of medical conditions for which topical therapy is appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions. Furthermore, Maxim is developing small-molecule inhibitors and activators of caspases, key enzymes that modulate and carry out the cellular signaling pathways involved in programmed cell death, also known as apoptosis. Compounds that can either inhibit caspases or induce caspases may form the basis for important new drugs for a wide variety of disease targets, such as cancer, cardiovascular disease and other degenerative diseases.
This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy and intended utilization of Maxamine, MaxDerm and the Company's caspase modulator technologies, and regarding Maxim's clinical trials. Such statements are only predictions and the Company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that the Company will not obtain approval to market its products and the risk that products that appeared promising in early research and clinical trials do not demonstrate efficacy in larger-scale clinical trials. These factors and others are more fully discussed in the Company's periodic reports and other filings with the Securities and Exchange Commission.
Note: Maxamine(R), Maxamine Therapy(TM), MaxDerm(TM) and the Maxim logo are trademarks of the company.
Editor's Note: This release is also available on the Internet at: http://www.maxim.com.
CONTACT: Maxim Pharmaceuticals Larry G. Stambaugh, President and CEO Dale A. Sander, Chief Financial Officer 858/453-4040 or Burns McClellan Ethan Denkensohn (Investors) Kathy Jones, Ph.D. (Media) 212/213-0006
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