First hESC Trial Kaput

Geron first filed its 21,000-page application for the Phase I trial in March 2008, and finally received approval from the US Food and Drug Administration in January 2009. The experimental therapy involved the injection of hESC-derived progenitors of neural support tissue into the spinal cord of patients with severe spinal cord injury. But then in August 2009, before any patients could receive the therapy, the FDA put a hold on the trial after continued animal experiments turned up a possible side effect of the treatment—microscopic cysts. The cysts appeared in low frequency, and did not appear to proliferate or cause any adverse effects on the animals, and in July 2010, the company announced the trial was back on track, after an additional preclinical animal study.

So far, four patients have been treated with the one-time injection of a low dose of cells as part of this initial safety trial. All four patients , who will continue to be monitored by Geron, have tolerated the treatments well and not shown any signs of adverse effects, according to the company, but so far, no patients have shown any neurologic changes that are consistent with efficacy. Patients who had already received approval to join the trial will still receive treatment, Stephen Kelsey, executive vice president and head of research & development, added at a press conference held today (November 15). Kelsey couldn’t say how many patients were in this position, but the company had originally aimed to enroll a total of eight patients in the trial.

“Deciding to move out of the stem cell business was a very difficult decision to make,” Geron CEO John Scarlett said at the press conference. “We’re making these changes because in the current environment of scarcity and uncertain economic conditions, we need to focus our resources on...our cancer programs,” which are expected to generate results as soon as next year. Stem cell trial results, Scarlett added, weren’t expected until 2014. “[It] was a business decision,” he said.

“Of course it would be best if this trial had gone forward,” Palay noted, “but as far as the future of the stem cell field...you should think of this as a very temporary setback.”

Indeed, there are still two ongoing hESC trials, both being conducted by Advanced Cell Technology, for two forms of genetic eye diseases—Stargardt's macular dystrophy and dry age-related macular degeneration. The results have not been made public yet, but “we’ve collected a great deal of data,” Lanza said, and “we couldn’t be more pleased with the results. ... I think it’s an exciting indication, and there’s every reason to be hopeful.”

And there will likely be more stem cells trials on the way, Konrad Hochedlinger of Harvard Medical School and Massachusetts General Hospital wrote in an email to The Scientist. “I think that others will pick up where Geron left off, but it may take a while for others to catch up.”

One thing working in the field’s favor is the fact that Geron helped pave the regulatory way for other stem cell therapies, said Sheng Ding, a stem cell biologist at the Gladstone Institutes and the University of California, San Francisco. “Geron's past efforts had cleared out a FDA path for pluripotent stem cells,” he wrote in an email to The Scientist. “With now more advanced and much better technologies to modify stem cells with much greater efficacy, some of the new stem cell products will succeed.”

Geron’s decision to terminate the trial also means that the company is eliminating 66 full-time positions—38 percent of its workforce. The company is actively seeking investors interested in acquiring the stem cell portion of its business.

For now, Geron will be focusing its efforts on its oncology programs. In particular, the company is currently testing its telomerase inhibitor, called Imetelstat, in several Phase II studies, including one for metastatic breast cancer and one for advanced non-small cell lung cancer. Geron’s LRP-directed peptide-drug conjugate program, which aims to use molecules to deliver anti-cancer drugs to brain tumors, also has a candidate entering two Phase II trials for brain metastases arising from non-small cell lung cancer and breast cancer.

“Both clinical stage molecules emerging from these programs are unique in their class and both currently represent the only molecules within their respective class to enter clinical trials,” Kelsey said. “Both programs address areas of large unmet medical need and have the potential to produce significant clinical impact on patient outcomes across a range of malignancies.”