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Active Biotech's Immunotherapy Anyara Is Down but Not Out

By Cormac Sheridan
Staff Writer

Shares in Active Biotech AB fell almost 13 percent Monday on news that its immunotherapy Anyara missed the primary endpoint of a Phase II/III trial in advanced renal cell cancer.

The trial was by no means a complete failure, however, as a subgroup analysis attained statistical significance in around a quarter of the patients recruited, and the Lund, Sweden-based company has a firm understanding of what happened from a biological perspective.

"We're encouraged that we got a robust signal," CEO Thomas Leanderson told BioWorld International. "You could say this was a Phase II/III trial, and we came in with Phase II data."

Anyara is a tumor-targeting superantigen comprising a modified version of the Staphylococcal enterotoxin A fused to the Fab portion of a monoclonal antibody that recognizes the 5T4 antigen, which is highly expressed in renal cell cancers.

The study, which began in 2007, recruited 513 patients who received either Anyara plus interferon alpha or interferon alpha alone. It failed to reach the primary endpoint of overall survival in the intent-to-treat population, but a subsequent analysis indicated that a majority of patients had pre-existing antibodies to the superantigen component of the protein.

The study was conducted in Eastern Europe. Leanderson said that the prevalence of antibodies to the superantigen is higher there than in Western Europe or the U.S., possibly because of a higher frequency of staphylococcus-related food poisoning. "I think that would be the obvious guess."

But patients who had low or normal levels of antibodies to the antigen, plus low levels of interleukin-6 (IL-6) – previously recognized as an independent marker for response to therapy in renal cell cancer – did achieve a survival benefit. The company is not disclosing the extent of that benefit (the full dataset will be reported at a medical conference), but the result was statistically significant both for overall survival (p = 0.02) and progression-free survival (PFS).

Active Biotech is confident that Anyara will be appropriate for 40 percent to 50 percent of patients in total, and it is now seeking a deal in order to further develop the therapy. Since the trial began, two kinase inhibitors have gained approval in the indication, Sutent (sunitinib malate; Pfizer Inc.) and Nexavar (sorafenib; Bayer Healthcare AG and Onyx Pharmaceuticals, Inc.). Anyara could potentially be positioned as a second- or third-line therapy alongside those drugs, Leanderson said. "It has a completely different mechanism. It's an immunotherapy."

Active Biotech has two other late-stage projects that kept a floor under its share price Monday. Its oral multiple sclerosis drug laquinimod, which is partnered with Teva Pharmaceutical Industries Ltd., of Petah Tikva, Israel, is under review in the European Union and will undergo a third Phase III trial in the U.S.

A Phase III trial of tasquinimod in advanced prostate cancer completed enrollment in December, although it is not yet clear when it will read out. "We will pass the PFS endpoint toward the end of this year," Leanderson said. However, Active Biotech and its partner, Paris-based Ipsen SA, will engage in discussions with the regulatory authorities to determine how to unblind the study.

The protocol allows for the use of additional therapies, and the recent approval of several in the indication means that many secondary endpoints could be corrupted by the effects of additional therapies after patients have completed the protocol. "The question is how to deal with that in the most productive way," he said.

Shares in Active Biotech (STOCKHOLM:ACTI) closed at SEK51:50 (US$8.02) Monday, down SEK7.50.