Shares of Point Therapeutics Inc. fell 68 percent to a 52-week low of 14 cents on Monday after the FDA placed a hold on the company's talabostat clinical program.

The hold followed an Independent Data Monitoring Committee's recommendation to halt two Phase III trials of talabostat in non-small cell lung cancer (NSCLC) after an interim analysis determined that neither trial was likely to meet its primary endpoint of median progression-free survival (PFS) or its secondary endpoint of overall survival.

In fact, in a trial evaluating talabostat plus Taxotere (docetaxel, Sanofi-Aventis Group) versus Taxotere plus placebo, the talabostat arm of the study demonstrated significantly lower overall survival than the placebo arm. The second trial was evaluating talabostat plus Alimta (pemetrexed, Eli Lilly & Co.) versus Alimta plus placebo.

The FDA-imposed clinical hold is not the first bad news to befall talabostat. In March, Point Therapeutics saw its shares drop 30 percent after it said that an open-label Phase II trial of talabostat plus Gemzar (gemcitabine, Eli Lilly) in advanced pancreatic cancer would not meet its primary endpoint of increasing six-month survival. (See BioWorld Today, March 2, 2007.)

In the aftermath of that Phase II set-back, the company's board of directors approved an unscheduled interim analysis of the talabostat-plus-Alimta Phase III trial, deciding to trade a small statistical penalty for a chance to see if the study was on track. At that point, the trial had enrolled 360 out of a planned 400 patients and achieved 150 events (disease progression or death). The talabostat-plus-Taxotere Phase III trial, on the other hand, was running behind schedule due to strict enrollment criteria and changes in the standard of care, so Point Therapeutics did not originally commit to an early look at its data.

But now both cats are out of the bag. President and CEO Don Kiepert said in a news release that the company is assessing its options and will "report on next steps once they have been decided."

Talabostat, a pan-inhibitor of dipeptidyl peptidase (DPP) enzymes, is Point Therapeutics' lead product and only clinical candidate. The drug is designed to inhibit fibroblast activation protein (FAP), suppressing tumor growth while stimulating cytokine and chemokine production to generate an immune response.

In an open-label Phase II NSCLC trial of talabostat plus Taxotere, six of 42 evaluable patients achieved a clinical response, with two achieving a complete response. In second-line patients, median survival was 10 months, compared to 7.5 months for Taxotere alone as cited in the Taxotere label. Phase II clinical response data in metastatic melanoma and chronic lymphocytic leukemia also were encouraging, but those programs were already on hold due to a lack of funding.

Also already on hold was Point Therapeutics' work on its preclinical programs: PT-630, a long-acting DPP inhibitor for diabetes and PT-510, a vaccine adjuvant for infectious diseases. These programs took a backseat as Point Therapeutics focused on talabostat.

As of March 31, Boston-based Point Therapeutics reported $9 million in cash and restricted cash, with a net loss of $5.3 million for the quarter. That loss should decrease significantly without the costs of Phase III trials, however, giving the company a bit more runway to evaluate its options.

For the day, Point Therapeutics (NASDAQ:POTP) fell 30 cents on Monday. n