Geron Announces Updated NCCN Guidelines® Recommending RYTELO™ (imetelstat) for the Treatment of Symptomatic Anemia in Patients with Lower-Risk MDS

Rhea-AI Summary

Geron (Nasdaq: GERN) announced that the National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines for Myelodysplastic Syndromes (MDS) to recommend RYTELO™ (imetelstat) as a Category 1 and 2A treatment for symptomatic anemia in lower-risk MDS patients. RYTELO is recommended as a Category 1 second-line treatment for both RS+ and RS- patients with serum EPO ≤500 mU/mL, and as a Category 2A first-line treatment for patients with serum EPO >500 mU/mL. This update follows the FDA's approval of RYTELO in June 2024 for treating adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia. The company believes these updates will increase awareness and uptake of RYTELO as a new treatment option for eligible lower-risk MDS patients.

Positive

• RYTELO received Category 1 and 2A recommendations in NCCN Guidelines for lower-risk MDS patients
• RYTELO is recommended as a first-line treatment for patients with serum EPO >500 mU/mL
• The update may increase awareness and uptake of RYTELO among hematologists
• FDA approval of RYTELO in June 2024 for treating adult patients with low- to intermediate-1 risk MDS

Negative

• None.

Insights

Medical Research Analyst

The inclusion of RYTELO™ (imetelstat) in the updated NCCN Guidelines for Myelodysplastic Syndromes (MDS) is a significant development for Geron As a Medical Research Analyst, I find this update particularly impactful for several reasons:

• RYTELO has received a Category 1 recommendation for second-line treatment, indicating a high level of evidence and uniform consensus among NCCN experts. This strong endorsement could significantly influence treatment decisions and potentially increase RYTELO's adoption rate.
• The Category 2A recommendation for first-line treatment in ESA-ineligible patients opens up a new market segment for RYTELO, potentially expanding its patient pool.
• The guidelines now recommend RYTELO for both RS+ and RS- patients, broadening its applicability across different MDS subtypes.
• Importantly, the guidelines do not specify red blood cell transfusion burden, which could allow for more flexible use of RYTELO in clinical practice.

These updates reflect the strength of Geron's Phase 3 data and could accelerate RYTELO's integration into standard treatment protocols. However, it's important to monitor real-world effectiveness and safety data as RYTELO's usage expands.

Financial Analyst

From a financial perspective, Geron 's announcement about RYTELO's inclusion in the NCCN Guidelines is highly positive. Here's why this news is significant for investors:

• The NCCN Guidelines are widely respected and often influence insurance coverage decisions. This inclusion could potentially lead to broader reimbursement for RYTELO, directly impacting Geron's revenue potential.
• The Category 1 and 2A recommendations position RYTELO favorably against competitors, potentially increasing its market share in the MDS treatment landscape.
• The expanded indications (RS+ and RS- patients, first and second-line treatments) could significantly enlarge RYTELO's addressable market, potentially boosting future sales.
• This update comes shortly after FDA approval and publication in The Lancet, creating a strong foundation for RYTELO's commercial success.

While it's too early to quantify the exact financial impact, this development could accelerate RYTELO's revenue ramp-up. Investors should closely monitor upcoming quarterly reports for early indicators of RYTELO's market penetration and sales growth. However, it's important to consider that market adoption of new therapies can take time and competition in the MDS space remains fierce.

Oncology Doctor

As an oncologist specializing in hematological malignancies, I find the updated NCCN Guidelines for RYTELO™ (imetelstat) in MDS treatment to be a game-changer. Here's my clinical perspective:

• The Category 1 recommendation for second-line treatment is based on high-level evidence, which is rare for MDS therapies. This gives clinicians more confidence in prescribing RYTELO after first-line treatments fail.
• RYTELO's recommendation for both RS+ and RS- patients is crucial, as it addresses a broader patient population than some existing therapies.
• The guideline's flexibility regarding serum EPO levels (≤500 mU/mL and >500 mU/mL) allows for more personalized treatment decisions.
• Importantly, RYTELO offers a new option for patients with high serum EPO levels who are often challenging to treat effectively.

However, it's essential to note that while these guidelines are promising, long-term follow-up data and real-world evidence will be important to fully understand RYTELO's place in MDS treatment. Clinicians should carefully consider individual patient factors, including comorbidities and treatment history, when deciding on RYTELO use. As we integrate RYTELO into clinical practice, monitoring for any unexpected side effects or long-term outcomes will be vital.

RYTELO, for both RS+ and RS- patients, has a Category 1 recommendation for second-line treatment and a Category 2A recommendation for first-line treatment of patients who are ESA ineligible (serum EPO >500 mU/mL)

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced that the National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of Myelodysplastic Syndromes (MDS) to recommend RYTELO™ (imetelstat) as a Category 1 and 2A treatment of symptomatic anemia in patients with lower-risk MDS. Treatments are classified as Category 1 and 2A when there is uniform NCCN consensus ≥85% that the intervention is appropriate.

The MDS NCCN Guidelines categorize lower-risk MDS patients without the del(5q) abnormality and with symptomatic anemia on the basis of ring sideroblasts (RS) percentage and serum EPO levels, without specifying red blood cell transfusion burden. For RS- lower-risk MDS patients with symptomatic anemia, RYTELO is recommended as a Category 1 second-line treatment after either erythropoiesis-stimulating agents (ESAs) or luspatercept in patients with serum EPO ≤500 mU/mL, and as a Category 2A first-line treatment in patients with serum EPO >500 mU/mL and unlikely to respond to immunosuppressive therapy. For RS+ lower-risk MDS patients with symptomatic anemia, RYTELO is recommended as a Category 1 second-line treatment after luspatercept in patients with serum EPO ≤500 mU/mL, and as a Category 2A first-line treatment in patients with serum EPO >500 mU/mL.

“We believe that the placement of RYTELO in the updated MDS NCCN Guidelines reflects the strength of our Phase 3 data and the U.S. Prescribing Information, and that these updates will help to increase awareness and uptake of RYTELO as a compelling new treatment option for these patients,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. “We are encouraged by the increasing dialogue across hematologists rethinking treatment approaches and sequencing given the availability of RYTELO for eligible lower-risk MDS patients with transfusion-dependent anemia.”

These updates to the MDS NCCN Guidelines follow the U.S. Food and Drug Administration’s (FDA) approval in June 2024 of RYTELO (imetelstat) for the treatment of adult patients with low- to intermediate-1 risk 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 ESAs, as well as publication of the IMerge Phase 3 pivotal trial data in The Lancet in December 2023.

National Comprehensive Cancer Network® (NCCN®) is a well-recognized, not-for-profit alliance of leading cancer centers in the United States. Its treatment practice guidelines, which are reviewed and updated on a continual basis to reflect the most current evidence, are widely respected and followed by the U.S. physician community and serve to inform and facilitate coverage decisions with payers for oncology therapies. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

About Lower-Risk Myelodysplastic Syndromes (LR-MDS)

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 survival^2,3. 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.

About RYTELO™ (imetelstat)

RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent 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 (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration.

Geron aims to ensure broad access to RYTELO for eligible patients. Accordingly, our REACH4RYTELO™ Patient Support Program provides a range of resources that support access and affordability to eligible patients prescribed RYTELO.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.

Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.

Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).

Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf.

About Geron

Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO™ (imetelstat) is FDA-approved for the treatment of adult patients with lower-risk MDS with transfusion dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or follow us on LinkedIn.

Use of Forward-Looking Statements

Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) Geron’s belief that placement of RYTELO in the updated MDS NCCN Guidelines reflects the strength of its Phase 3 data and the U.S. Prescribing Information, and that these updates will help to increase awareness and uptake of RYTELO as a compelling new treatment option for these patients; (ii) Geron being encouraged by the increasing dialogue across hematologists rethinking treatment approaches and sequencing given the availability of RYTELO for eligible lower-risk MDS patients with transfusion-dependent anemia; (iii) an unmet need for new treatments for patients with LR-MDS that can provide extended and continuous red blood cell transfusion independence; (iv) that inhibiting telomerase activity aims to potentially reduce proliferation and induce death of malignant cells; (v) that Geron aims to ensure broad access to RYTELO; (vi) that IMpactMF has registrational intent; and (vii) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of patients with LR-MDS with transfusion dependent anemia; (b) whether Geron overcomes potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether any future safety or efficacy results of imetelstat treatment cause the benefit-risk profile of imetelstat to become unacceptable; (e) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (f) that Geron may seek to raise substantial additional capital in order to continue the development and commercialization of imetelstat; (g) whether Geron meets its post-marketing requirements and commitments in the U.S. for RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact commercialization of RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia or the continuation of the IMpactMF trial; (i) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (j) whether the EMA will approve RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia and whether the FDA and EMA will approve imetelstat for other indications on the timelines expected, or at all. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2024, and subsequent filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances.

¹ Lewis R, Bewersdorf JP, Zeidan AM. Clinical Management of Anemia in Patients with Myelodysplastic Syndromes: An Update on Emerging Therapeutic Options. Cancer Manag Res. 2021 Jan 25;13:645-657. doi: 10.2147/CMAR.S240600. PMID: 33531837; PMCID: PMC7846829.

² Cogle CR, Reddy SR, Chang E, et al. Early treatment initiation in lower-risk myelodysplastic syndromes produces an earlier and higher rate of transfusion independence. Leuk Res. 2017;60:123-128.

³ Balducci, L. (2006), Transfusion independence in patients with myelodysplastic syndromes. Cancer, 106: 2087-2094. https://doi.org/10.1002/cncr.21860

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Aron Feingold

Vice President, Investor Relations and Corporate Communications

Kristen Kelleher

Associate Director, Investor Relations and Corporate Communications

investor@geron.com

media@geron.com

Source: Geron

FAQ

What is the new NCCN recommendation for RYTELO (imetelstat) in treating lower-risk MDS patients?

RYTELO (imetelstat) has been recommended as a Category 1 second-line treatment and Category 2A first-line treatment for symptomatic anemia in lower-risk MDS patients, depending on their ring sideroblasts status and serum EPO levels.

When was RYTELO (imetelstat) approved by the FDA for MDS treatment?

RYTELO (imetelstat) was approved by the FDA in June 2024 for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia.

How might the NCCN Guidelines update affect Geron (GERN) and RYTELO adoption?

Geron believes the NCCN Guidelines update will help increase awareness and uptake of RYTELO as a new treatment option for eligible lower-risk MDS patients, potentially benefiting the company's market position.

What patient group is RYTELO (imetelstat) recommended for as a first-line treatment according to the NCCN Guidelines?

RYTELO is recommended as a Category 2A first-line treatment for lower-risk MDS patients with serum EPO >500 mU/mL, for both RS+ and RS- patients.