Faye Feller, executive vice president and chief medical officer for the biopharma Geron, was giving her child a bath when her husband ran into the bathroom with her cellphone.
“Something’s going on at work,” he said. Geron’s blood cancer treatment, imetelstat (brand name Rytelo), a first-in-class telomerase inhibitor, had just received FDA approval.
Feller was immediately thrilled, but the news “really hit home” when she logged onto her company’s website following the announcement.
“I saw the popup that said, ‘Now approved. Rytelo in the U.S.,’” she said. “That brought tears to my eyes.”
In pharma and biotech, success is measured in decades. PhRMA estimates it takes an average of 10 to 15 years and $2.6 billion to develop one new medicine. Even by this standard, Rytelo’s path to approval was a long one. The drug had been in development for 33 years, including “about 20 years of development in patients,” Feller said.
“We've had a strong belief in bringing this mechanism to patients that has really persisted,” Feller said.
The mechanism is based on the Nobel Prize-winning science of telomeres, specialized DNA sequences at the ends of chromosomes that dictate the lifespan of a cell, and telomerase, an enzyme that lengthens telomeres and keeps the cell alive.
“Cancer cells upregulate telomerase in order to maintain immortality,” Feller said. “By targeting cancer cells that have this abnormally excessive expression of telomerase, we're getting down to treat an underlying cause of disease.”
After initial imetelstat studies in other cancers, investigators saw signals in hematological malignancies, Feller said. Now, Rytelo is approved in adult patients with lower-risk myelodysplastic syndromes (MDS) who have transfusion-dependent anemia. Because of their anemia, these patients become dependent on frequent red blood cell transfusions, which can reduce quality of life and shorten survival. Moreover, these patients need transfusions at least twice a month and monitoring in between.
“I believed in the team and I believed in the drug. I thought, as a drug developer, this was the most de-risked risk I could take.”
Faye Feller
Executive vice president, chief medical officer, Geron
Rytelo has the potential to allow patients to replace frequent and often unpredictable transfusions with a single monthly transfusion of the drug.
“We anticipate that this can ease some of the sociological [and] psychological burden of transfusions, in addition to the clinical benefits,” Feller said.
A winding path
Rytelo’s long journey to approval began when two scientists, Elizabeth Blackburn and Carol Greider, discovered telomerase in 1984. Eventually, that discovery led to breakthroughs for telomerase’s role in cancer; the formation of Geron, for which Blackburn and Greider were scientific advisors; and eventually, the Nobel Prize for the duo.
The drug had several stops and starts over the years as Geron looked for the appropriate cancer to target. Even after identifying hematologic myeloid malignancies, Geron experienced another bump in the road when, after four years, Janssen elected to terminate a collaboration and license agreement for developing and commercializing imetelstat.
The terminated deal was what brought Feller to Geron. Janssen had recruited her from Memorial Sloan Kettering Cancer Center in New York to work on imetelstat. After Janssen terminated the collaboration agreement, Feller and others moved to Geron to continue working on the drug. She called moving to a small biotech scary “but definitely worth it.”
“I believed in the team and I believed in the drug,” she said. “I thought, as a drug developer, this was the most de-risked risk I could take.”
In addition, Feller credits “a large investor community and financial institutions that also have this belief in the science and in the data and in the potential and have supported us along the way.”
Now, the company is commercializing Rytelo and advancing its larger pipeline, which comprises several programs in the discovery, preclinical and clinical stages, investigating telomerase inhibition across several myeloid hematologic malignancies.
Among them is a phase 3 trial of imetelstat in patients with JAK inhibitor relapsed/refractory myelofibrosis.
“We're pretty proud that we're the first study in this patient space to look at overall survival as a primary endpoint,” Feller said. “Once that study reads out successfully, that hopefully will be our next … indication.”
On the Rytelo commercialization side, Geron is planning a targeted launch “to a concentrated prescriber base of approximately 8,000 [healthcare providers]. This covers approximately 2,200 targeted accounts, where we expect around 70% of patients to be treated in the community hematology setting,” a company spokesperson told PharmaVoice via email. Geron expects Rytelo to be available in the distribution channel by the end of this month.
The company believes Rytelo can become part of the standard of care, since there’s high unmet need in the lower-risk MDP population and “approximately [10%] of lower-risk MDS patients … have very limited treatment options.” Other subsections of the population also have poorer outcomes and a high transfusion burden, the spokesperson said.
Updated forecasts show Rytelo sales will reach $791 million in 2028, which is higher than the $737 million predicted in April, and will reach more than $1 billion in 2030, an Evaluate spokesperson told PharmaVoice.
Now, Feller said there’s “huge enthusiasm and excitement” among physicians to bring Rytelo to patients. After popping that initial bottle of champagne, she’s continuing her focus on further advancing telomerase inhibitor technology.
“With the approval, we're transitioning … into a commercial company,” she said. “But it's really important to me and incumbent on me to maintain our strong development.”
