BioWorld International Correspondent

It's crunch time this week for Spanish firm Zeltia SA. Since late last month, the Madrid-based company has been engaged in an unusually vocal lobbying campaign on behalf of its cancer drug Yondelis, which the London-based European Medicines Evaluation Agency is currently evaluating.

A final determination is expected Thursday.

Zeltia went public last month, following what it regarded as an unexpectedly negative response to an oral presentation on Yondelis as a third-line therapy for soft tissue sarcoma, a rare type of malignant tumor that can develop in fat, muscle, nerve, joint, blood vessel or deep skin tissues.

Since then, it has been rallying support from national sarcoma groups across Europe and from individual experts in Europe and the U.S. Approval of Yondelis, the company's lead drug candidate, would validate its discovery platform, which is based on the isolation of novel bioactive compounds from marine organisms. It obtained the molecule, which modulates the expression of several genes involved in cell cycle progression, cellular growth and apoptosis, from the sea squirt Ecteinascidia turbinata.

At issue is the significance of the efficacy data obtained with Yondelis in the pivotal Phase II clinical trials that PharmaMar SA, Zeltia's drug discovery arm, presented for registration. It reported an overall, long-term response rate of 9.5 percent, meaning that tumor size shrunk by more than 50 percent in 9.5 percent of 63 patients in whom treatment with doxorubicin and ifosfamide failed. Twenty-two percent of patients experienced survival with no tumor progression during the first six months of treatment, and 26 percent of patients were still alive two years after commencing treatment.

"In soft tissue sarcoma, we think that is outstanding," Zeltia Chairman José Mar a Fern ndez Sousa-Faro told BioWorld International.

The burning question is whether those figures constitute sufficient justification for registration. For mainstream cancers, they would be regarded as being low, Fern ndez Sousa-Faro said, but the same criteria ought not to apply to soft tissue sarcoma, an orphan indication for which no new therapy has been approved in 25 years.

Fern ndez Sousa-Faro is critical of the EMEA on two fronts. The agency has indicated that it may require Zeltia to perform additional clinical trials to confirm Yondelis' efficacy. "They are asking for comparison studies, I suppose against placebo," he said. Yet such studies would be neither feasible nor meaningful. "The second paradox is that they have not called in a group of experts to explain to them what this is about," Fern ndez Sousa-Faro said.

An EMEA spokeswoman declined to comment on either claim, citing the agency's usual policy of not discussing products undergoing evaluation.

In the event of a negative decision, Zeltia can lodge an appeal; the entire process takes up to five months. But the company would not undertake any additional clinical studies in the absence of approval. "If we do not get approval in soft tissue sarcoma, we will switch the focus of development into ovarian cancer," Fern ndez Sousa-Faro said.

Zeltia has already reported positive Phase II data in that indication. It has also conducted Phase II studies of Yondelis in breast cancer and is now awaiting the results of 10 Phase I combination studies in order to determine the best development path for the product in that indication. Yondelis also has undergone a Phase II trial in endometrial cancer and a Phase I study in Ewing's sarcoma.

Zeltia has three other products in clinical development. Aplidin is in a Phase II trial for solid tumors, and last week gained European Orphan Drug status for treatment of acute lymphoblastic leukemia; Kahalalide F is undergoing a Phase II trial in liver carcinoma; and ES-285 is in a Phase I trial for solid tumors.