Washington Editor

OSI Pharmaceuticals Inc. said Aptosyn in combination with Taxotere missed its primary and secondary endpoints in a Phase III study in non-small-cell lung cancer patients.

However, the company's stock (NASDAQ:OSIP) moved up $1.32 Monday to close at $68.84.

Officials at Melville, N.Y.-based OSI could not be reached for comment, but Jason Zhang, senior biotechnology analyst with the Independent Research Group in New York, told BioWorld Today the negative outcome was anticipated.

Aptosyn (exisulind) is a cGMP phosphodiesterases inhibitor, which leads to the activation of the intracellular signaling protein, protein kinase G, and subsequent stimulation of apoptosis through the c-Jun kinase pathway. OSI is developing the drug as part of the Selective Apoptotic Anti-Neoplastic Drug platform it acquired via its $32 million stock acquisition of Cell Pathways Inc. in June 2003. (See BioWorld Today, Feb. 11, 2003.)

OSI inherited the fully enrolled, randomized, double-blind Phase III study designed to test overall survival in patients with advanced non-small-cell lung cancer (primary endpoint) and to demonstrate improvement in one-year survival, progression-free survival and response rate (secondary endpoints).

Indeed, OSI previously had said inadequate Phase II supporting data made the prospects for a successful Phase III trial relatively low.

Nevertheless, the 610-patient study evaluated Aptosyn in combination with Taxotere vs. Taxotere plus placebo in NSCLC patients after failure of prior platinum-based chemotherapy. (Taxotere, made by Aventis SA, of Strasbourg, France, is used in the second-line treatment of locally advanced or metastatic NSCLC.)

Survival in the Taxotere plus Aptosyn arm was essentially indistinguishable from that in the Taxotere plus placebo arm, the company said.

The median and one-year survival rates in the Aptosyn plus Taxotere arm were 6.9 months and 30.7 percent, compared with 6.9 months and 29.5 percent in the Taxotere plus placebo arm, respectively. Median progression-free survival was 13 weeks in the Taxotere plus Aptosyn arm and 12 weeks in the Taxotere plus placebo arm and the respective response rates were 9.2 percent and 7.2 percent.

Cell Pathways had initiated the Phase III based on preclinical data in orthotopic rat models and the combined safety database of successive clinical programs that originally focused on the pre-cancerous condition familial adenomatous polyposis, OSI said.

In September 2000, Aptosyn was rejected by the FDA as a treatment for patients with polyposis. (See BioWorld Today, Sept. 26, 2000.)

As part of the Cell Pathways acquisition, OSI also got CP461, a second-generation, more potent version of Aptosyn.

Zhang said CP461 holds little hope for OSI. "For this company at this time, the focus is Tarceva. I don't think [CP461 or Aptosyn] will impact the company at this time," he said.

Tarceva is a cancer drug being developed by OSI and its partners, Genentech Inc., of South San Francisco, and Roche Holdings Inc., of Basel, Switzerland. Data reported earlier this month showed a pivotal Phase III trial of Tarceva in advanced non-small-cell lung cancer demonstrated a 42.5 percent improvement in median survival and a 41 percent improvement in one-year survival rates, compared to placebo. (See BioWorld Today, June 8, 2004.)

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