Imetelstat (GRN 163L) shows promising results against brain cancer glioblastoma and prostate cancer...

In continuation of my update on Telomerase inhibitors, I find this info really interesting and hence sharing here with. As mentioned in my earlier blog about imetelstat (GRN163L )  has been undergoing Phase I clinical trials designed to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination, in solid tumors, chronic lymphoproliferative disease, multiple myeloma, lung and breast cancers and the company claims that Phase I objectives for imetelstat  (structure) have been achieved. Now  Dr. Jerry Shay, professor of cell biology of  The University of Texas Southwestern Medical Center at Dallas, claims that the same drug shows promise in fighting the brain cancer glioblastoma and prostate cancer.

Glioblastomas are the most common malignant brain tumors in adults, according to the American Cancer Society. They are difficult to treat with drugs because blood vessels in the brain have tightly constructed walls that allow only a few substances to pass through.

The researcher focused on cells called tumor-initiating cells. Some researchers believe that tumors contain a small subset of initiating cells – or cancer stem cells – that are able to initiate and drive tumors and that are often resistant to radiation therapy and chemotherapy.

In the glioblastoma study, Dr. Shay and his colleagues found that imetelstat blocked the action of telomerase in isolated tumor-initiating cells as well as the bulk of the tumor cells, eventually killing the cells. Combining imetelstat with radiation and a standard chemotherapy drug made imetelstat even more effective. When the researchers implanted human tumor-initiating cells into rodents, they found that imetelstat was able to enter brain tissue and inhibit telomerase activity.

In the prostate cancer study, the researchers isolated tumor-initiating cells from human prostate cancer cells. The cells showed significant telomerase activity. Imetelstat blocked the enzyme’s activity, and telomeres shortened greatly. As per Dr.Shay, since the drug attacks a mechanism that is active in most cancers, it might prove to be widely useful, especially when combined with other therapies.

Hope  Geron people must be really happy for these results  and conclusions.....

Ref : http://www.utsouthwestern.edu/utsw/cda/dept353744/files/570509.html

FDA Approves Rytelo (imetelstat) for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia

Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced that the U.S. Food and Drug Administration (FDA) has approved Rytelo™ (imetelstat) for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent (TD) anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).

“With the approval and availability of Rytelo, we believe eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia,” said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. “The approval of Rytelo as the first telomerase inhibitor is a testament to the power of our science and the passion of our people to innovate in the field of blood cancer. As we celebrate today’s momentous milestone, I would like to thank the patients and families, advocates, clinicians, study coordinators and site personnel, scientists, and Geron employees and collaborators past and present whose participation was integral to this achievement and to supporting our transformation into a commercial company.”

Lower-risk myelodysplastic syndromes (LR-MDS) is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue1. These symptomatic LR-MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short- and long-term clinical consequences that reduce quality of life and shorten survival2,3. There is a high unmet need for many LR-MDS patients, particularly those with characteristics having poorer prognosis. Current treatment options for those failing ESA are limited to select sub-populations and there is an unmet need for treatments that can provide extended and continuous red blood cell transfusion independence.

Approval Based on Results from IMerge Phase 3 Clinical Trial

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of Rytelo potentially practice changing for us,” said Rami Komrokji, MD, Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, who was an investigator of the pivotal IMerge clinical trial. “What is exciting about Rytelo is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias. The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.”

The FDA approval of Rytelo is based on results from the IMerge Phase 3 clinical trial, published in The Lancet 4. The IMerge trial met its primary and key secondary endpoints, with Rytelo demonstrating significantly higher rates of red blood cell transfusion independence (RBC-TI) versus placebo for at least eight consecutive weeks (Rytelo 39.8% [95% CI 30.9–49.3]; placebo 15.0% [7.1–26.6]; p<0.001) and for at least 24 weeks (Rytelo 28.0% [95% CI 20.1-37.0]; placebo 3.3% [95% CI 0.4-11.5]; p<0.001). RBC-TI was durable and sustained in the Rytelo treated population, with a median RBC-TI duration for 8-week responders and 24-week responders of approximately 1 year and 1.5 years, respectively.

In an exploratory analysis of Rytelo-treated patients achieving ≥8-week RBC-TI, median increases in hemoglobin were 3.6 g/dL for Rytelo and 0.8 g/dL for placebo. Clinically meaningful efficacy results were observed across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category.

In the IMerge trial, the safety profile of Rytelo was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most common Grade 3/4 adverse reactions were neutropenia (72%) and thrombocytopenia (65%), which lasted a median duration of less than two weeks, and in more than 80% of patients were resolved to Grade < 2 in under four weeks. Cytopenias were generally manageable with dose modifications. The intravenous administration of Rytelo every four weeks aligns to routine blood count monitoring for these patients.

The most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets (thrombocytopenia), decreased white blood cells, decreased neutrophils (neutropenia), increased aspartate aminotransferase (AST), increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Clinically relevant adverse reactions in < 5% of patients who received Rytelo included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension.

REF: https://en.wikipedia.org/wiki/Imetelstat

FDA Approves Rytelo (imetelstat) for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia

Presentations on Geron's Telomerase Inhibitor at AACR Special Conference

In continuation of my update on Geron's Telomerase Inhibitor..... Geron Corporation, announced several presentations at the American Association for Cancer Research (AACR) Special Conference on The Role of Telomeres and Telomerase in Cancer Research held in Fort Worth, TX between February 27th and March 1st. The conference comprised ten scientific sessions with over fifty oral presentations.

Geron scientists and collaborators presented recent data on the company's telomerase inhibitor, imetelstat sodium (GRN163L), And highlighted the drug's activity against cancer stem cells. As per the claim by the CMO & EVP, Stephen M. Kelsey,   the telomerase inhibitor is showing anti-cancer stem cell activity in a range of preclinical models. In Phase II trials of imetelstat starting this year Greron is targeting malignancies that are thought to be driven, at least in part, by cancer stem cells ....

Ref: http://www.geron.com/media/pressview.aspx?id=1213