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hESC Therapy Pioneer Geron Abandons Stem Cell R&D
By Nuala Moran
BioWorld International Correspondent
After 15 years' effort, the world pioneer of human embryonic stem cell (hESC) therapy, Geron Inc., is abandoning the field and will be stopping recruitment to its ground-breaking Phase I acute spinal injury trial.
"We are making the changes because of capital scarcity and uncertain economic conditions," said CEO John Scarlett, who was appointed to run the Menlo Park, Calif.-based company at the end of September. He has since instituted a review of the costs, value inflection points and the clinical, manufacturing and regulatory complexities associated with hESCs and concluded that Geron should drop cell therapy and focus on its telomerase inhibitor programs in cancer.
The decision wipes out the leading corporate force in hESC translation and commercialization. As a company, Geron has taken hESCs from initial discovery to FDA clearance for a clinical trial, with every step on the way requiring invention and negotiation. Scarlett said dropping hESCs was "a very difficult decision to make," and he is now looking for a partner to take up the mantle.
Geron's move was greeted with dismay by others involved in the development of embryonic stem cells, who were keen to stress the ax has fallen because of the economics of developing hESCs and not because they lack medical potential.
Ben Sykes, executive director of the UK's National Stem Cell Network, said it is "disappointing" that Geron has taken the decision to stop its spinal cord injury study.
"It is entirely clear that the decision is based on business reasons and not on the results achieved in the clinical trial so far," Sykes said.
Stephanie Williams, CEO of the Spinal Cord Injury Network in Australia, agreed. "It seems a great loss that a clinical trial that required so much effort to establish, and went through a rigorous FDA approval process, should falter due to adverse economic conditions. The spinal cord injury field stood to learn a great deal about cellular therapies in humans from this trial and now much of this huge opportunity has been lost," she noted.
Ending its stem cell research will see Geron eliminating 66 full-time positions out of a total work force of 175, generating restructuring costs of $8 million between now and the end of March 2012. The company expects to have cash of around $150 million at the end of 2011, of which it will spend $60 million to $65 million in 2012. Increasing investment in the oncology programs will result in the same cash burn as in 2011, but David Greenwood, president of Geron, said that without the changes the company would have been spending a further $25 million per annum on its hESC efforts over the next few years.
On chopping the stem cell programs, Geron has repaid $6.25 million in grant money to the California Institute for Regenerative Medicine, which in May announced it was giving the company $25 million funding to support the spinal injury trial.
There will be enough cash to reach six clinical development milestones expected for Geron's two Phase II oncology programs over the next 20 months. "By narrowing the focus, we will have sufficient financial resources to meet these near-term value inflection points," Scarlett said, adding, "This would not be possible if we continue to fund the stem cell programs at the current levels."
To date, the spinal injury trial of GRNOPC1, containing oligodendrocyte progenitor cells derived from hESCs, has recruited four of eight patients. Those patients will continue to be followed. Scarlett said no more patients will join the trial unless they have already consented but he would not disclose if any have done so.
Stephen Kelsey, Geron's chief medical officer, said results of the GRNOPC1 study to date are "remarkably consistent" with regards to the safety profile, and it seems unlikely that recruiting the other four patients would yield much incremental safety data. "We have not reported anything that could be construed as efficacy at this point; we have not observed any neurologic changes that would be consistent with efficacy," he said.
The oligodendrocyte progenitor cells in GRNOPC1 have demonstrated remyelinating, nerve growth-stimulating and angiogenic properties, which lead to restoration of function in rodent models of acute spinal cord injury.
Scarlett said a "number of conversations are going on with potential partners" for the hESC portfolio, but he added, "These are very early programs, and there are a relatively modest numbers of companies invested in the space."
In contrast, the oncology programs are both in Phase II, with Imetelstat, Geron's lead telomerase inhibitor in four studies in non-small-cell lung cancer, breast cancer, essential thrombocythemia and multiple myeloma. The company expects top-line data from those trials before the end of the fourth quarter of 2012.
Meanwhile, GRN1005, an LRP-directed peptide-drug conjugate, is entering two Phase II trials this year, one for brain metastases arising from non-small-cell lung cancer and the other for brain metastases from breast cancer. Data from the studies will be available before the end of the second quarter of 2013.
"In prioritizing their anticancer drugs over stem cell-based products, Geron's decision illustrates the difficulties and costs of bringing stem cell-based therapies to the clinic," said Charles ffrench-Constant, director of the Centre for Regenerative Medicine Edinburgh University in the UK.
"They have however made enormous advances in defining the various issues that need to be considered for stem cell therapies, advances that will be of huge value to others in the field," he added.