안녕하세요 보스턴 임박사입니다.

Geron이 10여년동안 개발하고 있던 Imeltestat (GRN163L)에 대해 이전에 글을 쓴 적이 있습니다.

BIOTECH (26) – Geron의 Telomerase inhibitor, Imetelstat 임상3상 결과

당시에 MDS (myelodysplastic syndrome)에 대한 임상3상 결과가 좋아서 FDA 승인이 기대가 되는 상황이었습니다. 오늘 FDA의 Advisory Committee Meeting이 있었는데 12:2로 승인을 하는 쪽으로 결론이 났습니다. 물론 FDA가 이 결정에 따룰 이유는 없지만 그래도 최종 결정에 긍정적인 결과를 주리라고 기대합니다.’

현재 MDS의 치료제로는 erythropoiesis-stimulating agents (ESA)가 거의 유일한 치료제라고 해도 무방한데 Geron은 Imeltestat을 ESA에 듣지 않는 환자들에 대한 치료제로 승인 요청을 할 예정입니다. Imetelstat에 대한 PDUFA date는 6월 16일입니다.

FDA adcomm votes in favor of Geron’s anemia drug for cancer patients despite questions on risk – Endpoints News 3/14/2024

Members of the FDA’s Oncologic Drugs Advisory Committee voted 12 to 2 on Thursday that the benefits of Geron’s imetelstat outweigh safety risks for the treatment of certain anemic myelodysplastic syndrome (MDS) patients who are dependent on blood transfusions.

While regulators raised concerns around cases of cytopenia, or low levels of white blood cells or platelets, advisory committee members said they were confident that the risks appear manageable. The FDA noted on Thursday that there was a “notably higher” incidence of neutropenia and thrombocytopenia in the imetelstat arm of a Phase III trial.

“Though I am concerned about the risks in this total trial population — in other words, not just the responders — I do believe it is more likely than not that there is a quality-of-life benefit here that is real,” University of Colorado associate professor Christopher Lieu said.

Stanford University School of Medicine professor Ranjana Advani added, “The community of doctors who take care of these patients know how to manage these side effects.”

Members also pointed to the fact that imetelstat met its primary endpoint in a Phase III trial, helping patients achieve eight-week red blood cell-transfusion independence, as well as a key secondary endpoint measuring 24-week independence.

MDS occurs when the normal production of blood cells is disrupted. Most patients with lower-risk MDS experience anemia, which can cause symptoms ranging from fatigue to irregular heartbeat and has also been linked to shorter survival. Those with severe anemia may be dependent on continuous transfusions. Patients who spoke during the adcomm stressed that frequent transfusions impacts their quality of life.

Ravi Madan, a senior clinician head at the National Cancer Institute’s Center for Cancer Research, was one of two members who voted against imetelstat’s benefit-risk analysis.

“I interpreted the question pretty strictly,” he said. “Even low-risk MDS patients are at high risk from their disease, but they shouldn’t also be at risk from their treatments as well.”

The FDA also raised concerns in briefing documents published in advance of the meeting that a majority of patients in the only randomized efficacy trial for imetelstat were enrolled outside of the US. Geron’s chief medical officer Faye Feller acknowledged that a majority of patients were from the EU, but assured the committee that “overall, the demographics are representative of the US MDS population.”

Traditionally, a class of drugs called erythropoiesis-stimulating agents (ESA) have been used off-label to treat lower-risk MDS patients with transfusion-dependent anemia. Bristol Myers Squibb’s Revlimid and Reblozyl are approved to treat anemia in MDS patients, and last year Reblozyl won a label expansion for first-line lower-risk patients who may require transfusions.

But Vanderbilt University School of Medicine professor Michael Savona, who was a member of the steering committee for imetelstat’s Phase III trial, said the use of those drugs is restricted to specific subgroups of patients.

“After failure of ESAs there is no good therapy for most patients,” he said during the meeting.

Geron is seeking approval for patients who have failed on or are ineligible for ESA treatment.

Johnson & Johnson saw early potential in imetelstat, shelling out $35 million upfront and promising another $900 million in milestones to partner on the drug a decade ago. The company backed out of the collaboration four years later, citing “a strategic portfolio evaluation and prioritization of assets.”