Ovarian Cancer

Zeltia: files for approval of Yondelis for ovarian cancer in the US

24th November 2008
By Sarah Oduekun

Zeltia seeks to add second indication for Yondelis in recurrent ovarian cancer.

Zeltia/Johnson & Johnson are seeking US approval for Yondelis, following a pivotal Phase III trial in second-line ovarian cancer therapy. However, approval in this indication may only marginally increase the commercial potential of Yondelis, as competition from established platinum-based chemotherapy agents will restrict the drug’s market potential.

Zeltia has announced positive results from the pivotal Phase III trial (OVA-301) for its ovarian cancer treatment, Yondelis (trabectedin). The trial involved 672 patients with recurrent ovarian cancer who had received treatment with one platinum-based agent six months prior to trial entry. Patients were randomized to receive Doxil/Caelyx (pegylated liposomal doxorubicin; Johnson & Johnson/Schering-Plough) with or without Yondelis. The primary endpoint of the trial was progression-free survival, which was recorded at a median of 7.3 months for patients who received Yondelis and Doxil, compared to 5.8 months for those who received Doxil alone. Zeltia also reported increased response rates with the use of the Yondelis and Doxil combination (28%) versus Doxil alone (19%), as well as an improved toxicity profile.

Yondelis is a synthetic tetrahydroisoquinoline alkaloid, derived from the Caribbean sea squirt (Ecteinascidia turbinata). It binds to the minor groove of DNA, thereby interfering with cell division, gene transcription and DNA repair mechanisms. The drug received orphan drug designation from both the EMEA and the FDA for the second-line treatment of ovarian cancer in October 2003 and April 2005, respectively.

Ovarian cancer is the most frequent cause of gynecological cancer-related mortality. Incidence in the seven major markets is estimated to be just under 60,000 in 2008, 40% of which are US patients. Surgery is the primary treatment for ovarian cancer, and platinum-based chemotherapy is the standard of care for advanced patients. However, ovarian cancer patients often experience multiple tumor recurrence.

Yondelis’s chosen indication of platinum-sensitive patients who have received prior platinum-based treatment, however, exposes the drug to fierce competition. Because ovarian cancer is chemo-sensitive, patients are usually re-treated with the same platinum-based agents they initially received if they are still platinum-sensitive and more than six months have passed since the first treatment. Significantly, the use of generic drugs such as cisplatin and carboplatin will restrict clinicians from prescribing the more expensive Yondelis.

In addition, established drugs for this indication such as Doxil and Gemzar (gemcitabine; Eli Lilly) are more likely to be prescribed in this setting as clinicians are more familiar with them. Further competition to Yondelis’s market penetration may arise from late-stage pipeline drugs in this setting such as Avastin (bevacizumab; Genentech/Roche), which has shown promising results in Phase II trials.

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