After 33 years, Geron finally crosses FDA finish line with blood cancer med Rytelo

Once hailed as an anti-aging magic bullet, telomerase has failed to live up to the hype as it was profiled in a 1998 Los Angeles Times article: “Could immortality be within grasp? Scientists say yes.”

Hoping to turn the promise into reality in November of 1990 was Geron Corporation.

Thirty-three years after opening its doors, the Foster City, Calif.-based biotech has finally hit paydirt with the FDA approval of a first-in-class telomerase inhibitor.

The U.S. regulator has signed off on Rytelo (imetelstat) to treat a group of bone marrow disorders called myelodysplastic syndromes (MDS). Rytelo is for adults with low- to intermediate-risk MDS and transfusion-dependent anemia who have failed to respond to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

It was a challenging path all the way for Geron, which survived scrutiny in March before winning over the FDA’s Oncologic Drugs Advisory Committee, which voted 12-2 in favor of imetelstat's approval.

“The (approval) is a testament to the power of our science, the excellence of our clinical and regulatory execution and the authentic passion of our people to innovate treatment for patients in need,” John Scarlett, M.D., Geron’s CEO for the last 13 years, said on a Friday morning conference call.

With the nod, Geron’s share price increased by 22%. The company went public in 1996.

Geron has set the wholesale acquisition cost for a single-dose vial of 47 mg of Rytelo at $2,471, while a single-dose vial of an 188 mg dose goes for $9,884. Dosages are determined by a patient’s body weight.

Evaluate has estimated sales for Rytelo will reach $737 million in 2028.

Patients with MDS are at risk for infections and need red blood cell infusions, which can bring additional risks and a decreased quality of life. Those with MDS can develop organ failure and cardiovascular problems. In some patients, bone marrow transplants are needed.

Rytelo is designed to bind to the telomerase enzyme to inhibit its activity, killing the cancerous stem and progenitor cells in the bone marrow that cause MDS.

Three U.S. researchers were awarded a Nobel Prize in 2009 for their discovery of how chromosomes are protected by the enzyme telomerase. Developing drugs to counter their activity has been vexing, however, as most have been derailed by toxicity issues.

Of concern with imetelstat have been high rates of neutropenia and thrombocytopenia, low neutrophil counts and low platelet counts. In the phase 3 study that set up the approval of Rytelo, the rates of these complications were higher in patients taking imetelstat than placebo.

During Friday’s conference call, Geron’s chief medical officer Faye Feller said that close monitoring of patients and dose modifications can reduce the risks associated with taking the infused drug.

In the IMerge trial, imetelstat demonstrated its ability to relieve the transfusion burden for patients with lower-risk MDS. After eight weeks of treatment, 40% of patients on imetelstat didn’t need transfusions, versus 15% of those on placebo. As a secondary endpoint, after 24 weeks, those numbers were 28% and 3% respectively.

Geron’s ability to commercialize its first product will be tested. Last year, the company brought on several experienced execs—including Novartis veteran Lorraine Shui (VP of marketing) and AstraZeneca veteran Scott Hutson (VP of sales)—to help market the drug in the U.S.

It was a tough road to securing approval for Geron, which began a series of unsuccessful clinical trials in a variety of indications for imetelstat in 2005. Twelve years later, the company finally found a niche for the molecule, expanding a phase 2 trial to include MDS patients.