Bioworld interview with CEO Alan Moorehttp://www.pharmacychoice.com/News/a...icle_ID=584367
Despite promising data from an earlier midstage trial, Stem Cell Therapeutics Corp.'s stroke drug NTx-265, a combination of human chorionic gonadotropin and erythropoietin, failed to show a statistically significant improvement over placebo in a Phase IIb trial, sending shares of the Calgary, Alberta-based firm plunging 75 percent.
The stock (TSX Venture:SSS) dropped C30 cents to close Tuesday at C10 cents.
But it wasn't that the drug didn't work. Top-line data from the 96-patient Phase IIb trial, designated REGENESIS, showed substantial improvement in patients in the NTx-265 group, with a drop of 6.3+/-0.05 as measured by the National Institute of Health Stroke Scale (NIHSS). The problem was that the placebo worked slightly better, showing a drop of 7.3+/-0.9 NIHSS, results that surprised President and CEO Alan Moore, to say the least.
"You expect, of course, a placebo effect," he told BioWorld Today. "You always expect one. But we had expected a drop of 2 or 3 points at most."
Stem Cell Therapeutics will be rechecking dosages and blood levels to make sure those placebo numbers were correct. Meanwhile, it also will be analyzing results from several secondary endpoints, including the modified Rankin scale and Barthel Index. Those are just as important as the NIHSS scale and could offer clinical and regulatory paths forward if either or both yield positive data, Moore said.
"So the game isn't over yet," he added. "We're hoping one of the other endpoints will show something here."
Not that Stem Cell Therapeutics is the only firm to find stroke a particularly tough indication. Only tissue-plasminogen activator (tPA, sold as Activase by Roche AG) has gained FDA approval, but its use is limited and offers only a three-hour treatment window. Other products aimed at widening that window so far have been thwarted in the clinic, including San Carlos, Calif.-based Nuvelo Inc.'s recombinant direct-acting fibrinolytic alfimeprase and South San Francisco-based Renovis Inc.'s neuroprotectant NYX-059. (See BioWorld Today, Oct, 27, 2006, and Sept. 26, 2008.)
There are two Phase II-stage drugs currently looking for partners: Microplasmin, a truncated, stable form of plasmin from ThromboGenics NV, of Leuven, Belgium, and V10152, a recombinant human thrombolytic protein from Guildford, UK-based Vernalis plc. And Rehovot, Israel-based D-Pharm Ltd. recently moved into Phase III testing with DP-b99, a drug designed to competitively bind with metal ions to inhibit metal-dependent enzymes that are overexpressed in stroke.
But Stem Cell Therapeutics' NTx-265 is different from those clotbusters and neuroprotective agents. Hailed as a neuroregenerative drug, NTx-265 aims to replace brain cells that are lost or damaged by the stroke. Given to patients one to two days post-stroke, it's designed to stimulate the growth and differentiation of existing stem cells into functional neurons and direct motor, visual and cognitive recovery.
Data from an earlier open-label Phase IIa trial were promising. NTx-265 was found to be safe and showed improved clinical outcomes compared to published data on similar untreated stroke patients, as well as a trend toward reduced infarct volumes over time in comparison to previously published data.
The Phase IIb REGENESIS trial originally had been expected to enroll 120 patients, but the study was modified earlier this year after the firm was unable to recruit additional North American patients. The trial also had been placed on temporary clinical hold in 2008 following reports that 42 patients had died in a German study testing anemia drug Eprex (epoetin alfa, Janssen-Cilag) in stroke patients. (See BioWorld Today, Sept. 19, 2008.)
NTx-265 also is EPO-based, but Stem Cell Therapeutics has not seen any similar increase in mortality, Moore said. He added that further data from that German trial showed an imbalance of patients treated with tPA, so "we left tPA out" of the Phase IIb trial.
Theoretically, though, NTx-265 could be used with other agents such as clotbuster tPA, and Stem Cell Therapeutics might consider testing the two together in Phase III, he said.
An end-of-Phase II meeting is expected by the end of the year - around which time the company hopes to secure a partner for late-stage testing and commercialization - and for now, Stem Cell Therapeutics plans to keep moving the program forward.
"Everything before this said the regimen [of hCG and EPO] will work," Moore said. "So we don't think a spurious placebo effect means we should just walk away."
The company also is pursuing NTx-265 in traumatic brain injury in an ongoing Phase IIa trial. As in the stroke program, investigators again will be looking for signs of new neuron growth and direct functional recovery of motor, visual and cognitive capacity.
Stem Cell Therapeutics also has Prolactin, a regenerative treatment for multiple sclerosis. That program is set to start a proof-of-concept trial later this year.
The company, which has about C$3.5 million (US$3.27 million) in the bank, could pad its cash balance as warrants come due in June and October.
"That could potentially bring in a fair bit of money," Moore said, though, with only eight employees, the firm has been pretty successful in stretching its resources. Even with the full Phase IIb stroke trial ongoing, he added, the burn rate was only about $1 million per quarter.