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Oncothyreon in Stock Plunge On Stimuvax Phase III Miss


By Cormac Sheridan
Staff Writer

Oncothyreon Inc. lost more than half its value during early trading Wednesday after partner Merck KgaA disclosed that its cancer vaccine, L-BLP25 (Stimuvax), failed to meet the primary endpoint of overall survival in a pivotal Phase III trial in non-small-cell lung cancer (NSCLC).

Merck, of Darmstadt, Germany, did say that "notable treatment effects were seen for L-BLP25 in certain subgroups," but other than that it remained completely tightlipped about the outcome of the trial.

Oncothyreon executives are no wiser than anyone else about the implications of that statement. "This means there is nothing further I can share with you about the subgroup analysis," an audibly frustrated Bob Kirkman, CEO of Seattle-based Oncothyreon told investors on a conference call. "Merck has not made any of that information public."

Moreover, it is not yet clear when or where it plans to do so. "They have not given any guidance in that respect," Kirkman said, although he noted that next year's American Society for Clinical Oncology meeting, which kicks off in Chicago on May 31, could be a possible venue. The deadline for submission of abstracts is Feb. 5, 2013. However, given the top-line data, the START trial is unlikely to form the basis of a regulatory submission, Kirkman said.

In the meantime, Merck said it will continue to analyze and discuss the data with external experts and regulatory authorities over the coming months.

The study recruited more than 1,500 patients with nonresectable Stage IIIA or Stage IIIB NSCLC who were stable or who had responded to primary chemoradiotherapy. In addition to best supportive care, patients received either placebo or a single infusion of cyclophosphamide, followed by eight weekly subcutaneous vaccinations of L-BLP25 and maintenance doses every six weeks until disease progression.

L-BLP25 contains a 25 amino acid sequence derived from the mucin 1 (MUC-1) antigen, which is overexpressed in many tumors and plays roles in tumor-associated immune suppression, in mediating resistance to chemotherapy and in preventing apoptosis. It is administered in a liposomal formulation, which also contains the monophosphoryl lipid A, (MPL) adjuvant, and elicits a T-cell response only.

In a Phase IIb open-label trial, median survival time was 4.2 months longer in the vaccine-treated group (n=88) as compared with a placebo group (n=83). The three-year survival rate in the vaccine-treated group was almost double that of the control group (31 percent v. 17 percent; p = 0.035).

"The START trial was powered to show a six-month improvement in survival, assuming a 20-month survival in the control group, with a "p" value one-sided of less than 0.025," Merck spokesman Gangolf Schrimpf told BioWorld Today.

An Asian Phase III trial, called INSPIRE, is recruiting about 420 patients and is not expected to report data for several years. Its continuation will be subject to agreement with regulatory authorities.

Oncothyreon also has a Phase I trial of a more potent, next-generation successor to Stimuvax, ONT-10, in patients with solid tumors. The vaccine also targets MUC-1, but it contains a longer MUC-1 peptide fragment and is formulated with a synthetic adjuvant, pet lipid-A, which acts as a Toll-like receptor 4 (TLR4) agonist. It will complete that study, but further progress depends on understanding the outcome of the START trial. "Until we know what happened in the START trial, it doesn't make much sense to make a decision one way or the other," Kirkman said.

Investors already have made up their minds, however. Oncothyreon "is now a PI3K story," Cowen analyst Simos Simeonidis wrote in a research note, referencing Oncothyreon's PI3 kinase inhibitor PX-866, which is undergoing five Phase II trials, three of which are combination trials, in six cancer indications. Investors were never fully convinced about the potential of Stimuvax, in any case, he said, pointing to the company's enterprise value of just $200 million prior to Merck's disclosure.

Oncothyreon will have around $80 million in cash and equivalents by year-end, Kirkwood said, enough to fund the company for two years.

Shares in the company (NASDAQ:ONTY) fell 55 percent, or $$2.47, to close Wednesday at $2.03.

Merck (FRANKFURT:MRK) ended the day at €99.43 (US$131.77), down 2 percent.

Meanwhile, NovaRx Corp., of San Diego, has yet to report interim data from a Phase III trial in 506 NSCLC patients of belagenpumatucel-L (Lucanix), a whole tumor cell vaccine. The study, which is being conducted under an FDA special protocol assessment, was fully recruited in June. Also in Phase III in NSCLC is BV-NSCLC-001, a cancer vaccine developed by Aberdeen, Scotland-based Bioven (Europe) Ltd. That product, which targets epithelial growth factor, was in-licensed from the Center of Molecular Immunology in Havana, Cuba.