Study Of Yondelis(R) In Ovarian Cancer Shows Significant Prolongation In Progression Free Survival

Main Category: Ovarian Cancer
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials;  Women's Health / Gynecology
Article Date: 16 Sep 2008 - 4:00 PDT

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Positive final results of the Phase III randomized pivotal study of Yondelis® in ovarian cancer were presented during the Presidential Symposium at the ESMO congress in Stockholm.

ESMO selects clinical studies that may result in a change in the current standard of care for presentation at the 2008 Presidential Symposium.

In total, 672 patients in 124 hospitals across 21 countries worldwide were enrolled in the pivotal study OVA-301, initiated in 2005. This is the largest single clinical trial conducted to date in the relapsed ovarian cancer setting.

The primary endpoint, progression-free survival (PFS) was met. Median PFS was 7.3 months for patients who received the combination of trabectedin + Doxil® versus 5.8 months for those treated with Doxil® alone. The hazard ratio (HR) was 0.79, which represents a statistically significant (p=0.019) and clinically meaningful 21% reduction in the risk of progression or death during the observation period. This result, derived from an independent radiology review in patients with radiologically measurable disease, is consistent with the 28% risk reduction by the more clinically meaningful independent oncology review (HR=0.72; p= 0.0008), which takes into account clinical as well as imaging data in the assessment of progression. The independent oncology review results were well matched with assessments by the study investigators (HR= 0.72; p= 0.0002). Thus, all three measures of PFS consistently demonstrated a statistically significant and clinically meaningful prolongation in PFS. These results are supported by an increased response rate with the use of the trabectedin and Doxil® combination (28%) versus Doxil® alone (19%), as measured by a blinded radiology review.

A key secondary endpoint of OVA-301 is overall survival. The interim survival data presented at ESMO are immature (55% censored) and the final analysis will be conducted after the occurrence of 520 events. Nonetheless, a positive trend with a 15% reduction in the risk of death favored patients treated with the Yondelis® and Doxil® combination. Consistent with prior experience with Yondelis®, neutropenia was the most common toxicity (77%) in the combination arm compared with 38% of patients in the Doxil®-only arm, but there was a low incidence of toxicity with clinical consequences, such as febrile neutropenia (8%) and sepsis (1%) in the combination arm. Similarly, reversible liver enzyme (transaminase) elevations were more common with the combination although without permanent liver damage or other clinical consequences. The addition of trabectedin enabled a lower dose of Doxil®, which may have contributed to the lower incidence of Doxil®-related toxicity observed with the combination. Specifically, hand and foot syndrome was seen in 54% of patients receiving alone compared with 24% of patients treated with trabectedin + Doxil. Similarily, stomatitis occurred in fewer patients receiving the trabectedin + Doxil® combination (20%) compared with those receiving Doxil® monotherapy (33%).

The efficacy and safety data from OVA-301 support the use of the combination of trabectedin and Doxil®, a non-platinum-based regimen, which may be an alternative option in relapsed ovarian cancer.

PharmaMar plans to submit an application for marketing authorization for this indication to the European Medicines Agency (EMEA) in the final quarter of 2008. Ortho Biotech Products, L.P. has confirmed PharmaMar its plan to submit an NDA to the FDA before the end of 2008. The decision of the regulatory agencies on the approval of Yondelis® in ovarian cancer in the European Union and in the United States could take place in 2009.

Yondelis® has been designated orphan drug for the treatment of soft tissue sarcomas and ovarian cancer in the European Union, United States, and Switzerland.

Yondelis® is currently being developed by PharmaMar in partnership with Ortho Biotech Oncology Research & Development, a unit of Johnson & Johnson Pharmaceutical Research & Development L.L.C. According to the licensing agreement, PharmaMar will market Yondelis® in Europe (including Eastern Europe), while Ortho Biotech Products, L.P. will market Yondelis® in the United States, and Janssen Cilag in the rest of the world.

PharmaMar

PharmaMar is the world-leading biopharmaceutical company of the Zeltia Group, and is committed to advancing the treatment of cancer through the discovery and development of new marine-derived medicines. PharmaMar has four novel compounds in clinical development. Yondelis® has received Authorization for Commercialization from the European Commission for treating advanced soft tissue sarcoma. Yondelis® is currently being marketed in the European Union for the treatment of soft tissue sarcomas in adults after failure of standard therapy. Aplidin®, Zalypsis®, and Irvalec® are other marine-derived new agents in clinical development by PharmaMar, which also has a rich pipeline of preclinical candidates, and a strong R&D program.

Yondelis®

Ongoing Yondelis® is being developed studied in highly prevalent tumors such as prostate, breast and lung cancers. In addition, there are clinical studies in sarcoma including a multicenter, phase III study of Yondelis® as a first-line therapy in patients with tumors bearing translocations, and a Phase II in children with recurrent rhabdomyosarcoma, Ewing sarcoma and other soft tissue sarcomas.

Important note

PharmaMar, based in Madrid, Spain, is a subsidiary of Grupo Zeltia (Spanish Stock Exchange, ZEL) that has been listed on the Spanish Stock Exchange since 1963 and the Spanish continuous market since 1998. This document is a press release, not a brochure. This document does not constitute nor is it part of any offer or invitation to sell or issue any application of purchase, offer, or shares subscription of the Group. Likewise, this document nor its distribution is part or can be of base for any contract or investment decision and does not constitute any kind of recommendation in relation with the shares of the Company.

PharmaMar