ISIS 3521 Maintains Favorable Prolonged Survival and Strong Overall Response Rates in People With Non-Small Cell Lung Cancer, According to Phase I/II Trial
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Isis Pharmaceuticals Provides Study Update on Antisense Drug At AACR-NCI-EORTC Meeting
CARLSBAD, Calif., Oct. 30 /PRNewswire/ -- After more than 15 months median clinical follow-up, the anti-cancer antisense compound ISIS 3521 continues to show promising survival, time to tumor progression, and tumor response results in people with non-small cell lung cancer (NSCLC), according to updated data from a Phase I/II study. The updated study results of ISIS 3521 in combination with the standard chemotherapy agents carboplatin and paclitaxel, in patients with Stage IIIb and Stage IV NSCLC, were presented today at the ``Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications'' International Conference sponsored by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC) in Miami Beach, Florida. Alan Yuen, M.D., Assistant Professor of Medicine at Stanford University, presented the findings. ISIS 3521 was exclusively licensed to Eli Lilly and Company in August 2001. ISIS 3521 is being co-developed by Isis Pharmaceuticals, Inc. (Nasdaq: ISIP - news) and Eli Lilly and Company (NYSE: LLY - news).
The median survival time for the 53 patients in the trial is 15.9 months. Median survival of patients receiving standard chemotherapy alone is approximately eight months. Additionally, median time to progression of disease for patients involved in the study is 6.3 months. Of the 48 patients evaluable for response, 40 (83 percent) had a tumor response or stable disease. One patient experienced a complete response and 22 patients experienced a partial response, producing an objective response rate (complete plus partial responses) of 48 percent (23 of 48 patients). Complete and partial response is defined as a 50 percent or greater reduction in tumor size measurements. Additionally, six patients have experienced a minor response, defined as a 25-50 percent reduction in tumor size measurements, and 11 patients have had stabilization of their disease. ISIS 3521 was well tolerated in the study.
``As the data from this clinical trial mature, we remain impressed with the survival, time to progression, and response rate observed in people with advanced non-small cell lung cancer,'' said Dr. Yuen. ``These updated results extend the observations reported at the American Society of Clinical Oncology meeting earlier this year. We are encouraged that, pending the results of the ongoing Phase III trial, ISIS 3521 could be a meaningful addition to the treatment of this disease.''
Isis initiated a randomized Phase III clinical trial of ISIS 3521 in NSCLC in October 2000. The 600 patient Phase III trial is currently enrolling and will evaluate the ability of ISIS 3521 to safely prolong patients' lives when combined with carboplatin and paclitaxel.
``It is gratifying to see the data continue to be strong and consistent in this study with ISIS 3521. We are optimistic that the ongoing Phase III clinical trial will confirm the promising results presented at this meeting,'' said F. Andrew Dorr, M.D., Isis' Vice President and Chief Medical Officer. ``We are hopeful that ISIS 3521 may represent a new treatment approach for people with non-small cell lung cancer.''
Data from a Phase I clinical trial of ISIS 3521 in combination with cisplatin and Lilly's anti-cancer drug Gemzar® (gemcitabine) were also presented at the AACR-NCI-EORTC meeting. Dr. Miguel Villalona of Ohio State University presented results demonstrating that ISIS 3521 in combination with cisplatin and Gemzar was well tolerated by patients with a variety of solid tumors. There was no evidence of pharmacokinetic interaction among the three drugs, indicating that combining them does not alter how they are distributed or disposed of in the body. The combination of Gemzar and cisplatin is specifically approved for the treatment of advanced NSCLC in the U.S. A Phase II clinical trial of ISIS 3521 in combination with Gemzar and cisplatin in NSCLC is currently in progress.
ISIS 3521 is an investigational antisense anti-cancer compound that is a potent, selective inhibitor of protein kinase C-alpha (PKC-alpha) expression. PKC is a family of closely-related signal transduction proteins that regulate information flow in and out of cells and modulate cellular responses to environmental stimuli. The PKC family plays a role in normal cell function, and is also involved in abnormal cell growth. ISIS 3521 is an antisense compound that binds to an mRNA sequence specific to PKC-alpha and thus selectively inhibits production of this protein without inhibiting production of other proteins in the PKC family. Using antisense technology, it is possible to selectively inhibit a single family member that may play a role in disease while allowing other members of the family to continue to perform normal cellular functions. This high degree of specificity may provide antisense drugs with a substantial advantage over traditional small molecule drugs in many difficult to treat diseases.
According to the American Cancer Society, lung cancer is the leading cause of cancer death for both men and women. This year, approximately 169,500 new cases of lung cancer will be diagnosed and 157,400 Americans will die due to the disease. More people die of lung cancer than of colon, breast and prostate cancers combined. Non-small cell lung cancer is the most prevalent form of lung cancer, accounting for approximately 75 percent of lung cancer diagnoses in the U.S.
Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs. The company has commercialized its first product, Vitravene® (fomivirsen), to treat CMV-induced retinitis in AIDS patients. In addition, Isis has 12 products in its development pipeline with two in late-stage development and six in Phase II human clinical trials. ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small cell lung cancer. Isis is preparing to initiate a Phase III program for ISIS 2302 (alicaforsen), an ICAM-1 inhibitor, in Crohn's disease. Isis has a broad patent estate as the owner or exclusive licensee of more than 800 issued patents worldwide. Isis' GeneTrove(TM) division uses antisense to assist pharmaceutical industry partners in validating and prioritizing potential gene targets through customized services and access to an extensive gene function database. Ibis Therapeutics(TM) is a division focused on the discovery of small molecule drugs that bind to RNA. Additional information about Isis is available at www.isip.com.
This press release contains forward-looking statements about the potential of the investigational compound ISIS 3521 in the treatment of non-small cell lung cancer and the potential of antisense drug discovery and development efforts that reflect the current beliefs of Lilly and Isis. However, as with any pharmaceutical under development, there are substantial risks and uncertainties in the process of pharmaceutical discovery, development and regulatory review. There are no guarantees that future clinical trials will confirm the preliminary results referred to in this release or that ISIS 3521 will receive regulatory approvals or prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly and Isis' filings (for Isis please refer to Form 10Q for the period ended September 30, 2001) with the United States Securities and Exchange Commission. Lilly and Isis undertake no duty to update forward-looking statements.
Gemzar® (gemcitabine hydrochloride, Lilly)
GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis Pharmaceuticals, Inc.
Vitravene® (fomivirsen) is a registered trademark of Novartis AG.
SOURCE: Isis Pharmaceuticals, Inc. |
