Monday October 22, 3:03 am Eastern Time
Press Release
SOURCE: Maxim Pharmaceuticals
Maxim Researchers Make Keynote Presentation of Phase 3 Melanoma Data At European Cancer Conference, ECCO
Updated Data Demonstrates Statistically Significant Improvement in Survival in Overall Intent-to-Treat Population
LISBON, Portugal--(BW HealthWire)--Oct. 22, 2001-- Maxim Pharmaceuticals (Nasdaq:MAXM - news; SSE:MAXM) announced that Sanjiv S. Agarwala, M.D., Associate Medical Director of the Melanoma Center at the University of Pittsburgh Cancer Institute, will make a keynote presentation today at the European Cancer Conference (ECCO) in Lisbon, Portugal describing updated results from Maxim's U.S. Phase 3 trial of Ceplene(TM) (histamine dihydrochloride) in combination with interleukin-2 (IL-2) for the treatment of advanced metastatic melanoma patients.
Dr. Agarwala will present 24-month data for the intent-to-treat population of all advanced metastatic melanoma patients randomized into the U.S. Phase 3 trial demonstrating a statistically significant improvement in survival for patients treated with the combination of Ceplene and IL-2 (p=0.046) compared to patients treated with IL-2 alone.
Dr. Agarwala will also present data demonstrating that the Ceplene/IL-2 combination significantly increased survival in advanced metastatic melanoma patients with liver metastases (p=0.0028) and visceral disease (p=0.023), and in patients with ocular melanoma (p=0.0051). In addition, Steven O'Day, M.D., Director of Medical Oncology at the John Wayne Cancer Center, Santa Monica, California, will present updated safety results from the Phase 3 study and a follow-on Phase 2 study. Ceplene is an investigational drug and has not been approved by the U.S. Food and Drug Administration (FDA) or any international regulatory agency.
Overview of Presentations
A total of 305 patients participated in an open-label, parallel group, controlled, multi-center U.S. Phase 3 trial sponsored by Maxim to evaluate the effectiveness of treatment with the combination of Ceplene and IL-2 versus IL-2 alone in patients with advanced metastatic melanoma. This trial of the Ceplene/IL-2 combination was completed in March 2000 and was designed to allow these advanced-stage malignant melanoma patients to self-administer treatment at home.
The updated data Dr. Agarwala will present today at the ECCO conference includes the results of a 24-month follow up of advanced metastatic melanoma patients participating in the U.S. Phase 3 study. After 24 months of follow up, analysis of the intent-to-treat population consisting of all patients randomized into the trial demonstrates that patients treated with Ceplene plus IL-2 achieved a statistically significant improvement in survival compared to the control patients treated with IL-2 alone (p=0.046, n=305). Patients with liver metastases treated with Ceplene plus IL-2 achieved a statistically significant improvement in survival compared to the control patients treated with IL-2 alone (p=0.0028, n=129). The primary endpoint of the Phase 3 trial was survival duration evaluated by comparing Kaplan-Meier survival curves using the unadjusted Log-Rank statistical method. These updated results represent an improvement over the 12-month follow-up data presented last year which demonstrated statistically significant survival in the patients that had liver metastases (unadjusted p=0.004), but for which the survival improvement for all patients had not yet reached statistical significance (p=0.125).
``The fact that the longer follow-up period demonstrates an improvement in the results for the Ceplene/IL-2 combination compared to IL-2 alone is reassuring and emphasizes the need to complete the additional clinical work required to attain approval,'' said Dr. Agarwala.
``We are pleased, that as the trial has matured with an additional year of follow up, the Phase 3 data have retained their strong statistical significance in the liver metastases population and also reached statistical significance in the overall intent-to-treat population of 305 patients,'' said Kurt R. Gehlsen, Ph.D., Maxim's Senior Vice President, Development and Chief Technical Officer. ``These data demonstrate a long-term benefit for those patients treated with the Ceplene combination in this trial. We will consider these results in designing the analysis plans for our ongoing and future oncology studies to determine if longer follow-up times may be more appropriate to assess the full survival benefit of this drug candidate.''
Dr. Agarwala will also present data demonstrating that the Ceplene/IL-2 combination significantly increased survival in advanced metastatic melanoma patients with visceral disease (p=0.023, n=218). Lastly, Dr. Agarwala will present an analysis of 35 patients with ocular melanoma enrolled in the Phase 3 trial and an ongoing Phase 2 trial (the ``M103 trial''). Ocular melanoma, the most common intra-ocular malignancy, metastasizes to the liver in about two-thirds of patients, and these patients typically have a median survival of only two to seven months. Dr. Agarwala will report that the median survival for patients with ocular melanoma and liver metastases treated with Ceplene and IL-2 was 7.5 months compared to 3.9 months for patients receiving IL-2 alone (p=0.0051).
``Patients with ocular melanoma are a group with a consistently poor prognosis, and these patients are often excluded from clinical trials for metastatic melanoma,'' said Dr. Agarwala. ``The fact that the survival benefit shown with the Ceplene/IL-2 combination was also observed in the ocular melanoma population is an intriguing observation and warrants further study.''
Dr. O'Day will present today at the ECCO conference safety data from 391 patients participating in the U.S. Phase 3 trial as well as the Phase 2 M103 trial. In these studies 239 patients received the combination of Ceplene and IL-2, and 152 patients received the same dose of IL-2 alone. All therapy was administered in an outpatient, at-home setting. Safety and toxicity were assessed according to National Cancer Institute (NCI) Common Toxicity Criteria in all patients who received at least one dose of study drug. The conclusion of this assessment was that Ceplene does not add clinically significant grade 3 or 4 toxicity compared to IL-2 alone and may be safely administered in conjunction with a regimen of low-dose, subcutaneous IL-2.
Last year Maxim sought FDA approval of Ceplene for the treatment of advanced metastatic melanoma with liver metastases based on the Phase 3 M01 trial using the 12-month follow-up data that was available at the time of submission of the New Drug Application. The FDA determined that this single study would not be adequate to support approval. Maxim is working with the FDA to finalize a clinical development strategy to support U.S. approval of Ceplene in advanced metastatic melanoma with liver metastases. In addition, Maxim is considering filing for approval outside the United States in Europe and other key markets using the updated 24-month data from the U.S. Phase 3 trial and data from the M103 trial.
Maxim Overview
Maxim Pharmaceuticals is a global biopharmaceutical company with a diverse pipeline of product candidates for life-threatening cancers and hepatitis. Maxim's research and development programs are designed to provide hope to patients most in need by developing safe and effective product candidates that extend survival while maintaining quality of life. Maxim has attracted an experienced international management group and a team of employees dedicated to commercializing life-enhancing product candidates. Joining this motivated team in its mission are world-leading scientific and clinical investigators and major pharmaceutical development partners.
Ceplene, based on the naturally occurring molecule histamine, is designed to prevent or inhibit oxidative stress, thereby reversing immune suppression and protecting critical immune cells. Ceplene is administered in combination with cytokines such as IL-2 or interferon-alpha, a class of proteins that stimulate these same immune cells. Ceplene is currently being tested in Phase 3 cancer clinical trials for advanced metastatic melanoma and acute myelogenous leukemia. Phase 2 trials of Ceplene are also underway for the treatment of hepatitis C and advanced renal cell carcinoma. Maxim is also developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, that may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. Lastly, the Company's MaxDerm technology is 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.
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 Ceplene, the apoptosis modulator compounds and MaxDerm, and regarding the Company'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 products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in larger-scale clinical trials, the risk that the Company will not obtain approval to market its products, the risk that clinical trials may not commence when planned, and the risks associated with the dependence upon collaborative partners. These factors and others are more fully discussed in the Company's periodic reports and other filings with the Securities and Exchange Commission.
Note: Ceplene(TM), MaxDerm(TM) and the Maxim logo are trademarks of the Company.
Editor's Note: This release is also available on the Internet at maxim.com. |
