Second Primary Neoplasms

None By: Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene The steady increase in treatment advancements for chronic lymphocytic leukemia (CLL) has provided new hope for patients whose options were previously limited. Now, currently available treatments, such as Bruton’s tyrosine kinase (BTK) inhibitors, have become established standard of care in the first-line and refractory settings and have vastly improved patient treatment outcomes. Promising investigational therapies in development could further change the treatment landscape in these settings as well. But with more options available, the burden is on the scientific community to provide the most robust and clinically relevant data to support treatment decisions made by physicians and patients. The “gold standard” of making clinical treatment decisions is head-to-head randomized clinical trials, often comparing combinations of agents and even within a drug class. There have been recent head-to-head clinical trials of BTK inhibitors in R/R CLL, including BeiGene’s global Phase 3 ALPINE trial of BRUKINSA® (zanubrutinib) versus ibrutinib, in which BRUKINSA demonstrated sustained superiority in progression-free survival (PFS).[i] Acalabrutinib, another BTK inhibitor, has demonstrated improvement in PFS versus rituximab plus idelalisib/bendamustine in R/R CLL in the ASCEND trial and has also demonstrated PFS noninferiority versus ibrutinib in R/R CLL patients with chromosome 17p or 11q deletions in the ELEVATE-RR trial.[ii],[iii] However, there are currently no head-to-head clinical trials that compare this next generation of BTK inhibitors. In the absence of these trials, there are a variety of statistical methodologies available to researchers, aiming to derive “apples-to-apples” comparisons between existing data sets, such as matching adjusted indirect comparisons or “MAICs” and network meta-analyses. Healthcare providers, as well as broader audiences, should be aware of the limitations of MAIC analyses when comparing treatment options. It is important to remember they are meant to be hypothesis-generating and do not establish superior efficacy or safety of one drug over another. The end goal is to allow physicians and patients to make informed decisions, and that requires a commitment to transparency and rigor in the comparative analyses of data sets. A recently conducted MAIC presented at the 28th Annual International Congress on Hematologic Malignancies® (Shadman et al) evaluated the relative efficacy of BRUKINSA versus acalabrutinib in R/R CLL based on data from the Phase 3 ALPINE and Phase 3 ASCEND trials.[iv] The analysis was conducted to address significant limitations of a MAIC previously published in The American Journal of Hematology (Kittai et al), some of which were acknowledged by the study authors.[v] The Shadman et al MAIC suggested a progression-free survival (PFS) and complete response (CR) advantage for BRUKINSA versus acalabrutinib, as well as potentially improved overall survival. The results differ from the previous MAIC, likely because it addressed certain important limitations that precluded a robust efficacy comparison in the previous MAIC. Limitations of the prior MAIC included: Disparate Data Cut-offs: The Kittai et al MAIC had a ~17 month difference in the median efficacy data cut-offs used for each trial. The Shadman et al MAIC analysis used closely matched data cut-offs using most recent data from ALPINE, which was presented at the American Society of Hematology (ASH) Annual Meeting and Exposition 2023 and showed durable PFS response after a median study follow-up of 36.3 months, with only a 3-month difference.[vi]   Limited Matching Criteria: Variables with significant differences across trials, such as number of prior therapies, were not included in the Kittai et al MAIC. The Shadman et al MAIC used a comprehensive matching criteria.   No Adjustment for COVID-19: In the Kittai et al MAIC, the data cutoff used for ALPINE was August 2022 (post-pandemic), while the data cutoff for ASCEND was February 2020 (pre-pandemic). The Shadman et al MAIC adjusted for the disproportionate effects of COVID-19 on ALPINE patients, an important factor for patients with CLL.   Imbalanced Effective Sample Size: In the Kittai et al MAIC, 327 patients from ALPINE were compared with only 99 patients from ASCEND.  The Shadman et al MAIC balanced the populations being compared (185 from ALPINE and 155 from ASCEND). Patients and physicians deserve the most comprehensive and rigorous data sets when it comes to evaluating potential treatments. This is why BeiGene’s research and development team focuses on best-in-class science and research, such as our BRUKINSA clinical development program, and we strive to fulfill this mission each and every day. U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib) INDICATIONS BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). IMPORTANT SAFETY INFORMATION  Warnings and Precautions  Hemorrhage  Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients. Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.  Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.  Infections  Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately. Cytopenias Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients. Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.  Second Primary Malignancies  Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies. Cardiac Arrhythmias   Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients.  Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.   Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment. Embryo-Fetal Toxicity  Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.  Adverse Reactions  The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).   Drug Interactions  CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily.  For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.  CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.  Specific Populations  Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily. Please see full U.S. Prescribing Information including U.S. Patient Information at BRUKINSA.com.   [i] Brown JR, et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13. PMID: 36511784. [ii] Ghia P, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355. Epub 2020 May 27. PMID: 32459600. [iii] Sharman JP, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291. doi: 10.1016/S0140-6736(20)30262-2. Erratum in: Lancet. 2020 May 30;395(10238):1694. PMID: 32305093; PMCID: PMC8151619. [iv] Shadman M, Brown JR, Williams R, et al. Efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC). Presented at: 28th International Congress on Hematologic Malignancies; February 29 to March 3, 2024. Miami, Florida. [v] Kittai AS, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 Dec;98(12):E387-E390. doi: 10.1002/ajh.27110. Epub 2023 Oct 9. PMID: 37811799. [vi] Brown JR, et al. Extended follow-up of ALPINE randomized phase 3 study confirms sustained superior progression-free survival of zanubrutinib versus ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL). Presented at: 65th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2023; San Diego, California; Paper No. 0202. https://doi.org/10.1182/blood-2023-174289

Armenia and Nepal are the first of 29 countries to receive BRUKINSA SEATTLE & BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- The Max Foundation (Max), a global nonprofit organization dedicated to accelerating health equity by delivering medication, technology, and supportive services to patients worldwide, BeiGene, a global oncology company, and the BeiGene Foundation, a nonprofit charitable foundation, today announced that the first doses of BRUKINSA® (zanubrutinib) have been administered for the treatment of adult patients with chronic lymphocytic leukemia (CLL) to patients in Armenia and Nepal, as part of a three-year collaboration to provide access to the medicine in 29 low- and middle-income countries (LMICs). This press release features multimedia. View the full release here: “We are thrilled to share that the first group of people diagnosed with CLL in Armenia and Nepal have received treatment free of charge through our collaboration with BeiGene and the BeiGene Foundation,” said Pat Garcia-Gonzalez, CEO of Max. “BeiGene has demonstrated that it is possible for companies to provide access to innovative treatments to regions in the world where access is limited or unavailable during the same year a drug receives approval in the U.S. We look forward to working together to expand access to this much-needed treatment to more patients.” Last year, BeiGene joined Max’s Humanitarian Partnership for Access to Cancer Treatments (Humanitarian PACT), a collaboration among professional, nonprofit, and commercial organizations that share the commitment to increase global access to treatment, care, and support for people living with cancer. As a member of the Humanitarian PACT, BeiGene provided a monetary grant through the BeiGene Foundation and is providing BRUKINSA free of charge for eligible patients in a number of low- and middle-income countries. “BeiGene and Max share a commitment to advance global health equity and ensure that patients in underserved regions have access to the best possible cancer care. The administration of the first doses of BRUKINSA to patients with CLL in Armenia and Nepal under our collaboration with Max and the BeiGene Foundation represents a crucial step in achieving this mission,” said John V. Oyler, Co-Founder, Chairman and CEO at BeiGene. “We are honored to participate in this worthy collaboration and support Max’s efforts to deliver innovative cancer medicines to patients in need around the world.” “For many years, the treatment of blood cancer, particularly CLL, has posed and continues to pose a significant challenge in Armenia. New medicines and treatments have simply not been accessible to those in need,” said Karen Meliksetyan, M.D., Head of Bone Marrow Transplant Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia. “The donation of BRUKINSA presents a tremendous opportunity for our patients to access treatment and will have a positive impact on many patients.” CLL is the most common leukemia in adults, accounting for about one third of new cases of leukemia worldwidei. BeiGene and Max aim to provide access to CLL treatment to patients in need in 29 low- and middle-income countries. In each country, verified physicians within Max’s network will submit a request for treatment to Max for patients who are under their care and are candidates for BRUKINSA. Upon patient identity verification and CLL diagnosis confirmation, Max will deliver the treatment directly to the health institution providing care to the patient through well-established supply chains. About The Max Foundation The Max Foundation is a global health nonprofit organization dedicated to accelerating health equity. For 26 years, Max has pioneered practical, scalable, high-quality solutions to bring lifesaving treatments and patient-centered health care to more than 100,000 people living with cancer and critical illness in low- and middle-income countries. Max believes in a world where all people can access high-impact medicines, where geography is not destiny, and where everyone can strive for health with dignity and with hope. Learn more at . About BeiGene BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit and follow us on LinkedIn and X (formerly known as Twitter). About the BeiGene Foundation The BeiGene Foundation is a charitable organization established by BeiGene, Ltd. It is a separate legal entity from BeiGene, Ltd. with distinct legal restrictions. The foundation’s mission is to advance global health by improving access to high quality therapies to more people around the world focused on three strategic areas: health equity, disaster relief, and community engagement. IMPORTANT SAFETY INFORMATION Warnings and Precautions Hemorrhage Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients. Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage. Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding. Infections Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately. Cytopenias Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients. Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed. Second Primary Malignancies Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies. Cardiac Arrhythmias Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients. Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment. Embryo-Fetal Toxicity Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Adverse Reactions The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Drug Interactions CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily. CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers. Specific Populations Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily. Please see full U.S. Prescribing Information including U.S. Patient Information. BeiGene’s Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGene’s ability to provide access to innovative treatments to regions with limited access during the year a drug receives approval in the U.S.; BeiGene’s ability to treat more patient pursuant to this collaboration; BeiGene’s commitment to advance global health equity; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeiGene’s ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. ______________________________ i 2 Yao Y, Lin X, Li F, Jin J, Wang H. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Retrieved from

Geron's hopes of getting its investigational antisense oligonucleotide imetelstat approved for myelodysplastic syndromes (MDS), and eventually positioning it as a competitor to Bristol Myers Squibb's Reblozyl (luspatercept), may have been thrown into serious doubt ahead of an FDA advisory committee meeting this Thursday.Imetelstat is under review to treat transfusion-dependent anaemia in lower-risk MDS based on Phase III results from the IMerge trial where roughly 40% of patients given the telomerase inhibitor achieved the primary endpoint of independence from red-blood-cell transfusions (RBC-TI) at 8 weeks, compared to only 15% for placebo.Magnitude and durabilityDespite the Phase III win, FDA staff didn't seem convinced about how impactful that outcome was, noting that MDS experts generally consider only a 16-week or longer period of RBC-TI as clinically meaningful. That assessment was released in briefing documents Tuesday, dragging down Geron shares by 15%.The company did evaluate the rates of RBC-TI lasting over longer periods, but response rates tended to shrink as the target durations got longer. FDA staff said imetelstat had a response rate of 28% for RBC-TI lasting 24 weeks, while only 13.6% achieved 1-year RBC-TI in the primary analysis. The corresponding rates for placebo were 3.3% and 1.7%, respectively.Agency scientists also said the IMerge results are "not supportive of a disease-modifying treatment effect" in either extending overall survival (OS) or helping drive disease remission. Though not formally tested, the OS data showed a numerically higher percentage of deaths in the imetelstat arm compared to placebo at both the primary (16.1% vs. 13.3%) and updated analyses (29.7% vs. 25%)."Unlike growth factors such as ESAs (erythropoiesis stimulating agents) which artificially raise blood cell counts, imetelstat is purported to have a direct effect on the underlying MDS through telomerase inhibition resulting in cell-cycle arrest, apoptosis, or senescence of malignant cells. However, these OS results are not supportive of a substantial disease-modifying treatment effect," FDA staff reviewers said.Higher rates of cytopeniasMeanwhile, they also raised doubts about how applicable the IMerge results are for a US population. The vast majority of study participants (93%) in the trial were enrolled outside the country, and the primary efficacy result "varied greatly" between the US and non-US sites, according to FDA staff. Very few patients, for example, had had prior treatment with Reblozyl, an erythroid maturation agent approved since August as a frontline medicine for transfusion-dependent anaemia in lower-risk MDS patients.The agency's safety assessment was no rosier. At 91%, imetelstat was associated with nearly double the rate of Grade 3 or 4 treatment-emergent adverse events (TEAEs) than placebo (47%). Much of the difference was due to higher rates of cytopenias in the imetelstat arm, but even when thrombocytopenia and neutropenia cases were excluded from the analysis, Geron's drug was still associated with a higher rate of Grade 3-4 events (54% vs. 39%). In addition, there were 14 discontinuations with imetelstat compared to none for placebo.Geron previously said the adverse effects were not uncommon, adding "the side effects are short-lived and reversible."Analysts 'still confident'Nevertheless, Stifel analysts said in a recent note that while they expected "some volatility" in Geron shares due to possible skittish investor reaction to the AdCom briefing documents, they were "still confident" in imetelstat's regulatory and long-term commercial prospects."FDA's scathing clinical review of Phase III MEDALIST data and subsequent decision to broadly expand the [Reblozyl] label into 1L LR-MDS despite questionable COMMANDS data in a RS-negative patient population…represents our best surrogate for how this recently re-organised FDA division tasked with reviewing imetelstat perceives overall risk/benefit in this disease setting," they said.The analysts predict efficacy will likely be the "least controversial" topic of discussion, while safety topics are likely to expand "beyond the obvious (myelosuppression, hepatotoxicity) to also include secondary primary malignancy and disease progression/AML transformation risk."Last year, Geron CEO John Scarlett said the company anticipates a peak market potential of $1.2 billion for imetelstat in the US and some key EU countries by 2030.