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ASH Abstracts Release Has Geron Buyers Proliferating

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By Anette Breindl
Science Editor

Abstracts of the data that are to be presented at the American Society of Hematology’s annual meeting next month were released Thursday. And the biggest market response to trial data involved Geron Corp’s myelofibrosis drug Imetelstat. With data showing a 44 percent overall response rate, Geron’s stock price (NASDAQ:GERN) increased 45 percent to close at $5.21 on Thursday, after being as high as $7.79 in intraday trading.

The study is small, and the group of patients reported on in the abstract is smaller still – a total of 18 patients. But with four complete responses, one partial response and three clinical improvements, the data suggested that Imetelstat could be disease-modifying.

It’s a second lease on life for a drug that many analysts were ready to leave for dead after it failed clinical trials in two solid tumors – breast cancer and non-small-cell lung cancer. (See BioWorld Today, Sept. 11, 2012.)

Jakafi (ruxolitinib, Incyte Corp.), the first and so far only approved drug to treat myelofibrosis, improves clinical symptoms by reducing the swelling of the spleen that is one consequence of myelofibrosis. But the drug does not affect the course of the disease, which is characterized by overproduction of platelets and scarring of the bone marrow.

Geron executives gave a general update on Imetelstat during the company’s third quarter earnings call, although they had to refuse more questions than they answered, given that ASH’s embargo policy prohibits them from commenting on the abstract in any sort of specific way.

The company does plan to initiate a multicenter trial evaluating Imetelstat in the first half of 2014. It will give details on that trial in the first quarter of 2014.

JP Morgan research analyst Cory Kasimov cautioned that the complete and partial responses “are not responses as strictly defined by the International Working Group (IWG) criteria.” The responses reported in the abstract are based on improvements in the bone marrow and blood, while a response as defined by IWG criteria must include a clinical response – in practice, most often a reduction in spleen size. “We suspect that if they had seen clear spleen reduction/symptomatic benefit, it would be mentioned in the abstract,” he added. But “nonetheless, the bone marrow/blood responses are impressive,” particularly considering that Jakafi was approved without such effects.

Jakafi targets a specific mutation in the Janus kinase, but consensus is building that such mutations are actually not drivers of the disease. The Mayo Clinic’s Ayalew Tefferi – who will be presenting the Imetelstat data at ASH, and who has been publicly critical of the overall utility of JAK inhibitors in the myelofibrosis patient population – wrote in the ASH abstract that “JAK2 mutations are neither specific nor pathogenetically essential for the disease.”

Geron CEO John “Chip” Scarlett said during the call that Imetelstat “has the potential to address the underlying neoplasm.” The drug works by inhibiting the enzyme telomerase, which lengthens the tips of chromosomes, the telomeres. Telomeres usually shorten with each cell division and function as a molecular clock for cells, which die when their telomeres get too short. Keeping their telomeres long is one of the ways in which cancer cells are able to keep dividing indefinitely.

Company executives did not comment specifically on the analyses, or the state of the spleens of the patients in the trial. But complete and partial responses “are intended to signify disease modification,” Scarlett said. An enlarged spleen is a consequence of the disease processes, and so “if you get the underlying neoplasm to head in the right direction, most of these criteria would head in the right direction.”