European Commission Expands Approval of Bristol Myers Squibb’s Reblozyl® (luspatercept) to Include First-Line Treatment of Transfusion-Dependent Anemia in Adults with Lower-Risk Myelodysplastic Syndromes (LR-MDS)
- None.
- None.
Insights
The recent approval of Reblozyl for treating transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) by the European Commission marks a significant advance in the management of this condition. The Phase 3 COMMANDS study, which served as the basis for this approval, provides compelling evidence that Reblozyl can nearly double the rate of transfusion independence and increase hemoglobin levels compared to the traditional treatment, epoetin alfa.
From a medical research perspective, the introduction of Reblozyl as a first-line treatment is noteworthy because it addresses a substantial unmet need in the patient population with lower-risk MDS. The durability of the response, as indicated by the study, suggests that patients may experience a sustained quality of life improvement without the frequent need for transfusions, which are associated with significant healthcare costs and patient burden.
Moreover, the safety profile of Reblozyl aligning with previous studies is reassuring for both patients and healthcare providers. It is important to monitor post-marketing data to confirm these findings in a real-world setting, which could further solidify the drug's position in the treatment protocol for MDS.
Expanding the indication of Reblozyl within the European Union presents a notable development from a health economics standpoint. The potential for patients to achieve transfusion independence has profound implications for healthcare systems. Transfusions not only incur direct costs but also indirect costs due to associated complications and hospitalizations.
By reducing the dependency on transfusions, Reblozyl could lead to significant cost savings for national health services across the EU. However, the cost-effectiveness of Reblozyl will depend on its pricing compared to epoetin alfa and the long-term outcomes it enables. If Reblozyl can maintain its efficacy over time and prevent or delay progression to higher-risk MDS, the economic benefits could be substantial.
It is also important to consider the budget impact for healthcare payers, as the initial cost of novel treatments can be high. Future studies and real-world evidence will be critical in determining the full economic value of Reblozyl in the treatment landscape of MDS.
The expansion of Reblozyl's approval in the EU is a strategic milestone for Bristol Myers Squibb, potentially bolstering its market position in the hematology space. This approval could translate into increased market share and revenue growth for the company within the EU, given the drug's status as a first-in-class treatment for disease-related anemia in lower-risk MDS patients.
The competitive advantage gained by demonstrating superior efficacy over epoetin alfa, a well-established treatment, cannot be understated. It is likely to influence prescribing habits, especially in light of the growing emphasis on personalized medicine and the need for therapies with improved patient outcomes. The pharmaceutical market for MDS treatments is niche but growing and Reblozyl's approval may prompt competitors to accelerate the development of their own novel treatments.
However, the exclusion of Great Britain from the centralized marketing authorization could impact the overall market potential for Reblozyl in Europe. Companies in the biopharmaceutical sector often rely on such approvals to streamline the drug launch process across multiple countries. Bristol Myers Squibb will need to navigate the separate regulatory environment in Great Britain to access this market.
Approval of Reblozyl is based on head-to-head, pivotal Phase 3 COMMANDS study, in which Reblozyl nearly doubled the percentage of patients achieving transfusion independence and hemoglobin increase, along with increased durability compared to epoetin alfa
This is the fourth authorized indication in
“With this approval for Reblozyl as a first-line treatment for anemia in adults with lower-risk MDS, more patients in the EU will have the potential to become transfusion independent for longer periods of time compared to current options available,” said Monica Shaw, M.D., senior vice president and head of European Markets, Bristol Myers Squibb. “This milestone underscores our ongoing commitment to developing new options for patients with disease-related anemia.”
The approval is based on the pivotal Phase 3 COMMANDS study, in which Reblozyl demonstrated superior efficacy compared to epoetin alfa, an erythropoiesis stimulating agent, in the study’s primary endpoint of concurrent red blood cell transfusion independence and hemoglobin increase. Safety results were consistent with previous MDS studies and were in line with expected symptoms in this patient population. Reblozyl is also approved in
“In the treatment of lower-risk MDS, few patients experience a lasting response to erythroid stimulating agents, leaving a critical need for more effective treatment options to address the burden of their anemia,” said Matteo Giovanni Della Porta, M.D., study investigator and head of Leukemia Unit at Humanitas Cancer Center in
*Centralized Marketing Authorization does not include approval in
About COMMANDS
COMMANDS (NCT03682536) is a Phase 3, open-label, randomized study evaluating the efficacy and safety of Reblozyl versus epoetin alfa for the treatment of anemia due to very low-, low- or intermediate-risk (IPSS-R) myelodysplastic syndromes (MDS) in patients who are red blood cell (RBC) transfusion dependent and were erythropoiesis stimulating agent (ESA)-naïve.
The primary endpoint evaluated in this study is RBC transfusion independence (RBC-TI) for 12 weeks with a mean hemoglobin (Hb) increase ≥1.5 g/dL. Key secondary endpoints include erythroid response (HI-E) of at least 8 weeks during weeks 1-24 of the study, RBC-TI ≥12 weeks and RBC-TI for 24 weeks. Eligible patients were ≥18 years old with lower-risk MDS who require transfusions. Patients were randomized 1:1 to receive subcutaneous Reblozyl (starting dose 1.0 mg/kg, titration up to 1.75 mg/kg) once every 3 weeks or epoetin alfa (starting dose 450 IU/kg, titration up to 1050 IU/kg) weekly for ≥24 weeks.
At the time of the primary analysis (March 31, 2023), 363 patients were randomized 1:1 to Reblozyl and epoetin alfa. Results from the primary analysis of the intent to treat (ITT) population showed:
-
60.4% (n=110) of patients receiving Reblozyl vs.34.8% (n=63) of patients receiving epoetin alfa achieved the primary endpoint of RBC-TI of at least 12 weeks with concurrent mean Hb increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001). -
HI-E increase of at least 8 weeks was achieved by
74.2% (n=135) of Reblozyl patients vs.53% (n=96) of epoetin alfa patients (p<0.0001). -
RBC-TI of at least 12 weeks was achieved by
68.1% (n=124) of Reblozyl patients vs.48.6% (n=88) of epoetin alfa patients (p<0.0001). -
Duration of response was 128.1 weeks (108.3-NE) for Reblozyl in patients who achieved TI for at least 12 weeks (achieved weeks 1-24) compared to 89.7 weeks (55.9-157.3) for epoetin alfa (Hazard Ratio [HR]: 0.534;
95% Confidence Interval [CI]: 0.330-0.864, p=0.0096).
Safety results were consistent with previous MDS studies, and progression to acute myeloid leukemia and total deaths were similar between both arms of the study. The most common treatment-emergent adverse events in at least
About MDS
Myelodysplastic syndromes (MDS) are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells (RBC), white blood cells and platelets, which can lead to anemia and frequent or severe infections. People with MDS who develop anemia often require blood transfusions to increase the number of healthy RBCs in circulation. Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections. Patients who become RBC transfusion-dependent have a significantly shorter overall survival than those who are not dependent on transfusions, partially due to iron overload or to more severe bone marrow disease than in non-transfusion dependent patients.
About Reblozyl® (luspatercept)
REBLOZYL, a first-in-class therapeutic option, promotes expansion and maturation of late-stage red blood cells in animal models. Reblozyl is being developed and commercialized through a global collaboration and North American co-promotion with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.
E.U. Indications:
REBLOZYL is indicated in the E.U. for the treatment of:
- adult patients with transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS).
- adult patients with anaemia associated with transfusion-dependent and non-transfusion-dependent beta-thalassaemia.
A European Summary of Product Characteristics for REBLOZYL is available from the European Medicines Agency website at www.ema.europa.eu.
REBLOZYL is indicated in the
- anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
- anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.
- anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. In the
WARNINGS AND PRECAUTIONS
Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (
Hypertension
Hypertension was reported in
Extramedullary Hematopoietic (EMH) Masses
In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in
In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in
Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses.
Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.
ADVERSE REACTIONS
Beta-Thalassemia
Serious adverse reactions occurred in
Most common adverse reactions (at least
ESA-naïve adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥
The most common (≥
ESA-refractory or -intolerant adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥
The most common (≥
LACTATION
It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.
DRUG ABUSE POTENTIAL
Abuse: Abuse of REBLOZYL may be seen in athletes for the effects on erythropoiesis. Misuse of drugs that increase erythropoiesis, such as REBLOZYL, by healthy persons may lead to polycythemia, which may be associated with life-threatening cardiovascular complications.
Please see accompanying
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Forward-Looking Statement of Bristol Myers Squibb
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that the outcome of pricing and reimbursement negotiations in individual countries in
Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
corporatefinancial-news
View source version on businesswire.com: https://www.businesswire.com/news/home/20240402231542/en/
BMS Contacts:
Media Inquiries:
media@bms.com
Investors:
investor.relations@bms.com
Source: Bristol Myers Squibb
FAQ
What is the expanded approval from the European Commission for Bristol Myers Squibb (BMY) regarding?
What study was the approval of Reblozyl based on?
Where is Reblozyl already approved for the first-line treatment of anemia associated with lower-risk MDS?