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Merck to Move Forward with Oncothyreon Cancer Vaccine

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By Catherine Shaffer
Staff Writer

An anxious wait for Oncothyreon Inc. has come to an end, as Merck KGaA announced it would continue development of tecemotide (formerly Stimuvax) following last year’s Phase III trial miss. That trial (START) did not meet its primary endpoint of improving overall survival, but a subgroup analysis of patients who received tecemotide after concurrent chemoradiotherapy showed a boost of just over 10 months in overall survival (30.8 months compared to 20.6 months in patients treated with placebo, p = 0.016).

The Darmstadt, Germany-based company will launch a new Phase III trial (START2) in patients with unresectable, locally advanced Stage III non-small-cell lung cancer (NSCLC). Oncothyreon stock (NASDAQ:ONTY) gained 38 cents, or 21 percent, to close at $2.18 Wednesday.

“We’re definitely pleased and excited that they decided to go forward,” Oncothyreon CEO Robert Kirkman told BioWorld Today. Kirkman clarified that Seattle-based Oncothyreon is not collaborating with Merck. “This is a straight outlicense . . . for us this is a financial matter with potentially significant upside should the product succeed.”

The move on Merck’s part has set rumors flying of a potential acquisition. “We believe it makes a lot of sense for Merck KGaA to acquire Oncothyreon, especially given its currently depressed valuation, and the high probability, in our view, that tecemotide succeeds in the START2 Phase III trial, when it reads out in a number of years,” wrote Simos Simeonidas, an analyst with Cowen and Co.

The risk for Merck, according to Simeonidas, is that Oncothyreon could license its follow-on vaccine, ONT-10, to another big pharma company, that could then compete head-to-head with Merck. Oncothyreon also has rights to an attractive royalty stream that would be an enticement for acquisition by another pharma company.

Kirkman declined to comment on the potential for acquisition of Oncothyreon by Merck, but he emphasized the importance of ONT-10 in the company’s pipeline. “That is wholly owned by us. It is not part of our relationship with Merck. We think this validation of MUC-1 as a target will be helpful to us as we consider further plans for ONT-10,” Kirkman said.

ONT-10 is completing its first clinical trial, a Phase I dose-escalation trial in patients with a variety of tumor types known to express MUC-1.

Merck reported in December 2012 that the START trial of tecemotide failed to meet its primary endpoint of overall survival, and mentioned at the time that treatment effects were seen in certain subgroups. However, until now it has not released further information about those treatment effects. (See BioWorld Today, Dec. 16, 2012.)

The START trial 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 tecemotide and maintenance doses every six weeks until disease progression.

Tecemotide 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 vs. 17 percent; p = 0.035).

Merck’s START2 trial will be a Phase III, multicenter, randomized, double-blind, placebo-controlled trial to assess efficacy, safety and tolerability of tecemotide in patients with unresectable, locally advanced NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent chemoradiotherapy. The primary endpoint will be overall survival.

Merck has reached an agreement with the FDA for a special protocol assessment for the trial. Kirkman said that the trial “will look a lot like the trial they just ran, but focus on the subgroup where they saw the positive data.”

Simeonidas said that Merck’s decision to continue developing tecemotide was “very positive news” for Oncothyreon because it allows further funding and development of the asset and provides external validation of the START data, as well as making the company an acquisition target.

He noted that many investors had written off tecemotide because they didn’t believe that the subgroup analysis would yield anything of value and did not believe Merck would invest in another Phase III trial, or “even if they did believe these data, knowing that the answer to the second Phase III trial is years away, did not care,” Simeonidas wrote. “We believe that another factor could come into play a lot sooner than the START2 data read out: we believe that Merck KGaA may end up acquiring Oncothyreon, even if only as a defensive move.”