Ortho Biotech submits NDA for Trabectedin in relapsed ovarian cancer
Sunesis Pharmaceuticals, Inc. presented data from three clinical trials of the company’s lead drug candidate, voreloxin (formerly SNS-595), at the Chemotherapy Foundation Symposium held in New York on November 4-8. Data previously presented from Phase 1 and Phase 1b/2 studies in patients with acute myeloid leukemia (AML) showed that preliminary clinical responses were observed in
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Ortho Biotech Products, L.P. has announced the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for trabectedin when administered in combination with DOXIL (doxorubicin HCI liposome injection) for the treatment of women with relapsed ovarian cancer (ROC).
If approved, trabectedin combined with DOXIL will provide a new, non-platinum treatment option for these patients in the United States.
The application follows the completion of a multicenter, randomized Phase III study, ET743-OVA-301, one of the largest studies conducted in ROC, comparing the combination of trabectedin and DOXIL to DOXIL alone in 672 patients. The study showed that patients treated with the combination treatment had a statistically significant improvement in the primary endpoint of progression-free survival (PFS, or the length of time during and after treatment in which the disease does not progress) compared to patients treated with DOXIL alone.
“This is a significant milestone in the development of trabectedin, an agent with a novel mechanism of action that holds promise for patients with relapsed ovarian cancer,” said Craig Tendler, M.D., Vice President, Medical Affairs, Oncology/ Nephrology, Ortho Biotech Products, L.P. “We are confident in the strength of the data supporting the application and look forward to working with the FDA throughout the regulatory review process.”
Relapsed ovarian cancer refers to epithelial carcinoma of the ovary that recurs after treatment. According to the National Cancer Institute (NCI), it is estimated that 21,650 women will be diagnosed with, and 15,520 women will die from ovarian cancer in the U.S. in 2008.
Trabectedin is being developed under a license from PharmaMar, and DOXIL is marketed by Ortho Biotech Products, L.P. in the U.S.
The ET743-OVA-301 Study
Patients were enrolled at 124 centers in 21 countries. Per the study protocol, the data were evaluated by a blinded, independent radiology review and a blinded, independent oncology review. The trabectedin/DOXIL combination demonstrated a statistically significant improvement in PFS compared to DOXIL alone (median PFS 7.3 versus 5.8 months, respectively) and a statistically significant reduction of 21% in the risk of progression or death during the observation period in the independent review of patients with radiologically measurable disease (HR=0.79, 95% CI (0.65;0.96), p=0.0190). This result is consistent with the results of the independent oncology review that takes into account clinical as well as imaging data in the assessment of progression. In this review, there was a 28% risk reduction for disease progression or death with the trabectedin/DOXIL combination (HR=0.72, 95% CI (0.60; 0.88), p=0.0008).
Secondary endpoints included response rate, overall survival, and safety. A statistically significant increase in response rate was seen with the trabectedin and DOXIL combination (28%) compared to DOXIL alone (19%), as measured by the independent radiology review. A final protocol-specified survival analysis is planned after the occurrence of 520 events. The safety profile in the study was consistent with previous experience with trabectedin and DOXIL.
The most common adverse reactions (greater than or equal to 20%) for the trabectedin/DOXIL combination compared to DOXIL alone, respectively, were:
- Hematological reactions including neutropenia (77% versus 38%, with febrile neutropenia occurring in 8% of the cases and sepsis in 1% of the cases), leucopenia (48% versus 26%), anemia (48% versus 25%) and thrombocytopenia (36% versus 8%);
- Gastrointestinal reactions including nausea (74% versus 42%), vomiting (56% versus 30%) and diarrhea (26% versus 19%);
- Liver enzyme (transaminase) elevations were more common in the combination arm, but were generally reversible and not associated with evidence of chronic liver damage or other clinical consequences. These included increased alanine aminotransferase (55% versus 9%) and increased aspartate aminotransferase (40% versus 10%); and
- Fatigue (46% versus 36%).
Additionally, commonly associated DOXIL adverse events, such as hand-foot syndrome (HFS) and stomatitis, occurred in fewer patients receiving the combination compared to DOXIL alone (24% versus 54% and 20% versus 33%, respectively).
Trabectedin is a novel cytotoxic antitumor agent that was originally derived from the Caribbean tunicate, Ecteinascidia turbinate (”sea squirt”). The compound is now produced synthetically. Trabectedin binds to the minor groove of DNA, interfering with cell division and genetic transcription processes and DNA repair machinery. Trabectedin is currently in Phase III development in ovarian cancer and to expand its uses in sarcoma.
According to the licensing agreement, PharmaMar has rights to market the compound in Europe and Japan, while Ortho Biotech Products, L.P. has marketing rights for the product in the rest of the world.
Results from a Phase 3 study show that patients with metastatic breast cancer who were treated previously with an anthracycline in the adjuvant setting experienced a significant improvement in time to disease progression (TTP) and overall response rates after receiving a combination of Doxil (doxorubicin HCl liposome injection) and docetaxel as compared to docetaxel alone.
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Results of a phase III, international randomized clinical trial demonstrate a new standard of care for treating advanced ovarian cancer that significantly reduces side-effects and post-operative deaths compared to the previously established treatment course. The study, presented at the 12th Biennial Meeting of the International Gynecologic Cancer Society (IGCS) in Bangkok in October, has a
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Sunesis Pharmaceuticals, Inc. has announced a presentation of updated interim results from an ongoing Phase 2 clinical trial demonstrating that the Company’s lead product candidate, voreloxin, shows promising efficacy and safety as a single agent in patients with platinum-resistant ovarian cancer. Ovarian cancer remains an unmet medical need with high recurrence rates, and the
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A new epidemiological study has found that among women who have never used menopausal hormone therapy, obese women are at an increased risk of developing ovarian cancer compared with women of normal weight. Published in the February 15, 2009 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the research indicates that obesity
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A new epidemiological study has found that among women who have never used menopausal hormone therapy, obese women are at an increased risk of developing ovarian cancer compared with women of normal weight. Published in the February 15, 2009 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the research indicates that
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