Category: Healthcare

• FIGARO-DKD is the first contemporary cardiorenal outcomes trial with the majority of patients who had an eGFR ≥60 ml/min/1.73m² to show cardiovascular benefit in chronic kidney disease associated with type 2 diabetes; patients were included in this study if they had UACR levels 30–5000 mg/g¹
• Additionally, results from FIDELITY, a prespecified meta-analysis of Phase III trials FIDELIO-DKD and FIGARO-DKD comprising over 13,000 patients with chronic kidney disease associated with type 2 diabetes, showed that finerenone reduced the risk of the composite cardiovascular outcome of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure²
• Results of the FIGARO-DKD Phase III study and the FIDELITY prespecified meta-analysis were presented at ESC Congress 2021, with FIGARO-DKD simultaneously published in the New England Journal of Medicine

 

WHIPPANY, N.J. — (BUSINESS WIRE) — Bayer announced today that detailed results from the Phase III FIGARO-DKD study demonstrated that compared with placebo, KERENDIA^® (finerenone) – a first-in-class nonsteroidal mineralocorticoid receptor antagonist (MRA)^3,4 – significantly reduced the risk of the composite primary endpoint of time to first occurrence of cardiovascular (CV) death or nonfatal CV events (myocardial infarction, stroke or heart failure hospitalization) by 13% (relative risk reduction, HR 0.87 [95% CI, 0.76-0.98; P=0.0264]) over a median duration of follow-up of 3.4 years when added to maximum tolerated labeled dose of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).¹ The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure. These data were presented today during a Hot Line session at the ESC Congress 2021 and simultaneously published in the New England Journal of Medicine.

FIGARO-DKD is the first contemporary Phase III cardiorenal trial with the majority of patients with stages 1-2 CKD (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73m²) to show CV benefit in CKD associated with T2D.¹ Patients were included in this study if they had urine albumin-to-creatinine ratio (UACR) levels 30–5000 mg/g.¹ KERENDIA^® was approved in the United States on July 9, 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, nonfatal myocardial infarction and hospitalization for heart failure in adult patients with CKD associated with T2D.⁴

 

The KERENDIA^® label contains a Warning and Precaution that KERENDIA^® can cause hyperkalemia.⁴ For more information, see “Important Safety Information” below.

 

“The unfortunate reality is that patients living with chronic kidney disease associated with type 2 diabetes are three times more likely to die from a cardiovascular event than those with type 2 diabetes alone.⁵ As chronic kidney disease progresses, the risk for cardiovascular events and heart failure hospitalization increases, so early diagnosis and treatment is critical,”⁶ said Bertram Pitt, professor of medicine emeritus at the University of Michigan School of Medicine in Ann Arbor and co-principal investigator of the FIGARO-DKD clinical trial. “The FIGARO-DKD study adds to the body of evidence that supports the benefits of finerenone for patients with chronic kidney disease associated with type 2 diabetes.”^1,3,7

 

FIGARO-DKD: Second Phase III Study for Finerenone to Meet Primary Endpoint

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,437 participants from 48 countries to finerenone 10 mg or 20 mg orally once daily or placebo when added to standard of care, including blood glucose-lowering therapies and a maximum tolerated labeled dose of ACEis or ARBs.¹ Patients had UACR ≥30–<300 mg/g and eGFR ≥25–≤90 mL/min/1.73m² or UACR ≥300–≤5000 mg/g and eGFR ≥60 mL/min/1.73m².¹

 

In this study, the incidence of the key secondary endpoint, a composite of time to kidney failure, a sustained decrease of eGFR ≥40% from baseline over a period of at least four weeks, or renal death was lower with finerenone than with placebo, affecting 350 (9.5%) and 395 (10.8%) patients, respectively.¹ However, the difference was not statistically significant (HR 0.87 [95% CI, 0.76-1.01; P=0.0689]) over a median duration of follow-up of 3.4 years.¹ In the FIDELIO-DKD study, finerenone reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥40%, kidney failure or renal death (HR 0.82 [95% CI, 0.73-0.93; P=0.001]).⁴ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure. There were few renal deaths during the trial.⁴

 

In FIGARO-DKD, safety and tolerability profile were generally consistent with that of previously reported FIDELIO-DKD results. Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).¹ Hospitalization due to hyperkalemia for the finerenone group was 0.6% versus <0.1% in the placebo group, and there was no hyperkalemia-related death in either treatment group.¹ Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.¹

 

FIDELITY: Prespecified Meta-analysis

Also presented within the ESC Hot Line session were select data from FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: combined FIDELIO-DKD and FIGARO-DKD Trial program analYsis), which is a prespecified meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies. FIDELITY is a meta-analysis of the largest Phase III program to evaluate the occurrence of progression of kidney disease as well as fatal and nonfatal CV events in >13,000 adult patients with CKD associated with T2D.^2,7

 

In this prespecified exploratory meta-analysis, finerenone reduced the risk of the composite CV outcome of time to CV death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure by 14% compared with placebo.² The composite CV outcome occurred in 825 (12.7%) patients receiving finerenone and 939 (14.4%) patients receiving placebo (HR 0.86 [95% CI, 0.78–0.95]), with a number needed to treat of 46 at 36 months.² The reduction in the CV composite outcome was primarily driven by hospitalization for heart failure. Cardiovascular death and nonfatal myocardial infarction were directionally consistent with the CV composite outcome.² The composite kidney outcome of time to first onset of kidney failure, sustained ≥57% decrease in eGFR from baseline over ≥4 weeks, or renal death occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving placebo (HR 0.77 [95% CI, 0.67–0.88]).²

 

In FIDELIO-DKD, this exploratory composite kidney outcome of kidney failure, sustained decrease in eGFR by 57% or more from baseline, or renal death occurred in 252 (8.9%) patients and 326 (11.5%) patients in the finerenone and placebo groups, respectively (HR 0.76 [95% CI, 0.65–0.90]).³ In FIGARO-DKD, this exploratory composite kidney outcome of kidney failure, sustained decrease in eGFR by 57% or more from baseline, or renal death occurred in 108 (2.9%) patients and 139 (3.8%) patients in the finerenone and placebo groups, respectively (HR 0.77 [95% CI, 0.60–0.99]).¹ KERENDIA^® is not indicated to reduce the risk of renal death.⁴

 

“With the results of the FIGARO-DKD study and FIDELITY analysis, we are very pleased to build on our growing body of evidence for finerenone in patients with chronic kidney disease associated with type 2 diabetes,” said Amit Sharma, M.D., Vice President of Cardiovascular and Renal, Bayer U.S. Medical Affairs. “Together, these findings reinforce our commitment to improving the lives of these patients.”

 

About Finerenone Phase III Clinical Trials Program

Having randomized more than 13,000 patients with CKD associated with T2D around the world, the Phase III program with finerenone in CKD associated with T2D comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes.⁷

 

The FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study was a randomized, double-blind, placebo-controlled, multicenter study in adult patients with CKD associated with T2D, defined as either having an UACR of 30 to 300 mg/g, eGFR 25 to 60 mL/min/1.73 m² and diabetic retinopathy, or as having an UACR of ≥300 mg/g and an eGFR of 25 to 75 mL/min/1.73 m.^3,4 The trial excluded patients with known significant non-diabetic kidney disease and a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (NYHA class II to IV).⁴ All patients were to have a serum potassium ≤4.8 mEq/L at screening and be receiving standard of care background therapy, including a maximum tolerated labeled dose of an ACEi or ARB.⁴ A total of 5,674 patients were randomized to receive finerenone (N=2833) or placebo (N=2841) and were followed for a median of 2.6 years.⁴ The mean age of the study population was 66 years, and 70% of patients were male.⁴ The trial population was 63% White, 25% Asian, and 5% Black.⁴

 

Finerenone reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥40%, kidney failure, or renal death (HR 0.82 [95% CI, 0.73-0.93; P=0.001]).⁴ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.⁴ There were few renal deaths during the trial.⁴

 

Finerenone also reduced the incidence of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure (HR 0.86 [95% CI, 0.75-0.99; P=0.034]).⁴ The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.⁴ Adverse reactions that occurred more commonly on finerenone than on placebo, and in at least 1% of patients treated with finerenone, were hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%) and hyponatremia (1.4% vs. 0.7%).⁴

 

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) investigated the efficacy and safety of finerenone versus placebo in addition to standard of care on the reduction of cardiovascular morbidity and mortality in approximately 7,400 patients with CKD associated with T2D across 48 countries including sites in Europe, Japan, China and the U.S.^7,8 Finerenone 10 mg or 20 mg, orally once daily, was added to standard of care, including blood glucose-lowering therapies and a maximum tolerated labeled dose of an ACEi or an ARB.^7,8

 

Bayer also recently announced the initiation of the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III study that will investigate finerenone compared to placebo in more than 5,500 symptomatic heart failure patients (New York Heart Association class II-IV) with a left ventricular ejection fraction of ≥40%.⁹ The primary objective of the study is to demonstrate superiority of finerenone over placebo in reducing the rate of the composite endpoint of cardiovascular death and total (first and recurrent) heart failure (HF) events (defined as hospitalizations for HF or urgent HF visits).⁹

 

About KERENDIA

INDICATION:

• KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D)⁴

 

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors⁴
• Patients with adrenal insufficiency⁴

 

WARNINGS AND PRECAUTIONS:

• Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L⁴ 

  Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium⁴

 

MOST COMMON ADVERSE REACTIONS:

• Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo: hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%), and hyponatremia (1.4% vs. 0.7%)⁴

 

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice⁴
• Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate⁴
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers⁴

 

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment⁴
• Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B)⁴

 

Please read the Prescribing Information for KERENDIA.

 

About Chronic Kidney Disease Associated with Type 2 Diabetes

Patients with CKD associated with T2D are three times more likely to die from a cardiovascular-related cause than those with T2D alone.⁵ CKD is a serious and progressive condition that is generally underrecognized.¹⁰ CKD is a frequent complication arising from T2D and is also an independent risk factor of cardiovascular disease.^11,12,13 Approximately 40% of all patients with T2D develop CKD.¹¹ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and cardiovascular events.^12,13,14,15 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^16,17,18

 

About Bayer’s Commitment in Cardiovascular and Kidney Diseases

Bayer is an innovation leader in the area of cardiovascular diseases, with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. The heart and the kidneys are closely linked in health and disease, and Bayer is working in a wide range of therapeutic areas on new treatment approaches for cardiovascular and kidney diseases with high unmet medical needs. The cardiology franchise at Bayer already includes a number of products and several other compounds in various stages of preclinical and clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cardiovascular diseases are treated.

 

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2020, the Group employed around 100,000 people and had sales of 41.4 billion euros. R&D expenses before special items amounted to 4.9 billion euros. For more information, go to www.bayer.com.

 

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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

 

References

1. Pitt B. FIGARO-DKD: finerenone in patients with chronic kidney disease and type 2 diabetes. Oral presentation at: ESC Congress 2021: The Digital Experience. August 28, 2021. Sophia Antipolis, France. https://digital-congress.escardio.org/ESC-Congress/sessions/2831-hot-line-figaro-dkd-fidelity-analysis
2. Filippatos G. FIDELITY Analysis: finerenone in mild-to-severe chronic kidney disease and type 2 diabetes. Oral presentation at: ESC Congress 2021: The Digital Experience. August 28, 2021. Sophia Antipolis, France. https://digital-congress.escardio.org/ESC-Congress/sessions/2831-hot-line-figaro-dkd-fidelity-analysis
3. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229. doi:10.1056/NEJMoa2025845
4. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021.
5. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308. doi:10.1681/ASN.2012070718
6. Bansal N, Zelnick L, Bhat Z, et al. Burden and outcomes of heart failure hospitalizations in adults with chronic kidney disease. J Am Coll Cardiol. 2019;73(21):2691-2700. doi:10.1016/j.jacc.2019.02.071
7. Ruilope LM, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):345-356. doi:10.1159/000503712
8. Efficacy and safety of finerenone in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease (FIGARO-DKD). ClinicalTrials.gov. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT02545049
9. Study to evaluate the efficacy (effect on disease) and safety of finerenone on morbidity & mortality in participants with heart failure and left ventricular ejection fraction greater or equal to 40% (FINEARTS-HF). ClinicalTrials.gov. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT04435626
10. Breyer MD, Susztak K. Developing treatments for chronic kidney disease in the 21st century. Semin Nephrol. 2016;36(6):436-447. doi:10.1016/j.semnephrol.2016.08.001
11. Bailey R, Wang Y, Zhu V, Rupnow MFT. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7(1):415. doi:10.1186/1756-0500-7-415
12. Anders HJ, Huber TB, Isermann B, Schiffer M. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14(6):361-377. doi:10.1038/s41581-018-0001-y
13. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:15018. doi:10.1038/nrdp.2015.18
14. American Diabetes Association standards of medical care in diabetes – 2021. Diabetes Care. 2021;44(1):1-244. https://care.diabetesjournals.org/content/diacare/suppl/2020/12/09/44.Supplement_1.DC1/DC_44_S1_final_copyright_stamped.pdf
15. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:5-14. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
16. National diabetes statistics report 2020: estimates of diabetes and its burden in the United States. Center for Disease Control and Prevention. Accessed July 9, 2021. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
17. Stages of CKD. American Kidney Fund. Accessed May 11, 2021. https://www.kidneyfund.org/kidney-disease/chronic-kidney-disease-ckd/stages-of-chronic-kidney-disease/
18. Incidence, prevalence, patient characteristics, and treatment modalities. United States Renal Data System. Accessed July 9, 2021. https://adr.usrds.org/2020/end-stage-renal-disease/1-incidence-prevalence-patient-characteristics-and-treatment-modalities

Contacts

Media Contact:
Patti Fernandez, Tel. +1 845.300.4091

E-Mail: patricia.fernandez.ext@bayer.com

U.S. Food and Drug Administration assigned an action date of December 23, 2021

The sBLA is supported by the Phase 2 ABA2 Trial evaluating Orencia in adults and children to prevent aGvHD

If approved, Orencia would become the first therapy for the prevention of aGvHD

 

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #ABA2—Bristol Myers Squibb (NYSE:BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Orencia (abatacept) for the prevention of moderate to severe acute graft versus host disease (aGvHD) in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation (HSCT). The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 23, 2021.

“While stem cell transplants are an effective treatment for aggressive leukemias and other hematological malignancies, patients who receive stem cell transplants from unrelated and human leukocyte antigens (HLA)-mismatched donors are at high risk for developing aGvHD,” said study lead investigator Leslie Kean, M.D., PhD, Director of the Pediatric Stem Cell Transplantation Program, Boston Children’s Hospital/Dana-Farber Cancer Institute. “There is a tremendous need to expand the stem cell donor pool by lowering the risk of aGvHD in both adults and children receiving unrelated donor stem cell transplants.”

Stem cell transplants include infusion of donor T-cells, a type of white blood cell that recognizes and destroys foreign invaders in the recipient’s body, including cancer cells. GvHD occurs when the donor T-cells also recognize the patient’s healthy cells as foreign and start attacking healthy tissues and organs. To initiate this attack, T-cells require activation through a signaling process called co-stimulation. Between 30 and 70 percent of transplant recipients develop aGvHD, depending on donor type, transplant technique, and other features. Orencia, a therapy currently approved to treat various arthritic conditions, binds to and inhibits protein targets involved in co-stimulation, thus inhibiting T-cell activation.

“For patients who receive unrelated donor stem cell transplants, in particular for racial and ethnic minority patient populations, there is a heightened risk of developing aGvHD, a potentially life-threatening medical complication for which there are no approved preventive therapies,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “We look forward to working with the FDA to bring Orencia to this new patient population and employ pathbreaking science in an effort to address unmet needs of underserved patients.”

The sBLA submitted to the FDA is based on results from the Phase 2 ABA2 trial and a registry trial based on real world evidence. The ABA2 trial assessed the impact of Orencia on the prevention of severe aGvHD, when added to a standard GvHD prophylactic regimen administered to patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. A mismatch in HLA increases the risk of GvHD. Results from ABA2 showed that treatment with Orencia resulted in a significant reduction in severe aGvHD and associated morbidity without an increase in disease relapse. The findings of the real-world analysis were consistent with those of ABA2.

Bristol Myers Squibb thanks the patients and investigators who participated in this clinical trial.

About ABA2
The ABA2 study was a multicenter, Phase 2 investigator sponsored trial conducted by Dr. Leslie Kean of Boston Children’s Hospital/Dana Farber Cancer Institute. ABA2 had two cohorts: a single arm cohort for patients receiving transplants from mismatched unrelated donors (MMUD) (“7/8” cohort), and a randomized, double blind, placebo-controlled cohort for patients receiving transplants from 8/8 matched unrelated donors (MUD) (“8/8” cohort). All subjects received a calcineurin inhibitor (CNI), with dosing starting on day -2 and continuing through at least Day 100 as tolerated, and methotrexate (MTX) on days one, three, six and 11 (transplant day is Day 0). Orencia-treated subjects received 10 mg/kg Orencia on days -1, 5, 14 and 28.

In the ABA2 clinical trial, addition of Orencia to SOC aGvHD prophylaxis of MTX+CNI resulted in a significantly higher aGvHD-free survival (GFS) rate compared to registry controls in the single-arm 7/8 HLA-matched cohort, and numerically higher severe GFS rate in the double-blind, placebo-controlled 8/8 HLA-matched cohort at 180 days post-transplant.

About Acute Graft Versus Host Disease and Impact on a Diverse Patient Population

Graft versus host disease (GvHD) after a hematopoietic stem cell transplant occurs when transplanted donor T-cells recognize antigenic differences between the donor and the recipient, and attack the recipient’s healthy tissue and organs. Acute graft versus-host disease (aGvHD) impacts between 30 and 70 percent of patients, depending on donor type, transplant technique, and other features, with racial and ethnic minority patient populations more likely to experience challenges following a hematopoietic stem cell transplantation. This may be due to several factors that impact overall outcome, including a lack of donor availability and related care. This activation of T-cells can result in severe immune-mediated tissue damage to the host, with the skin, liver and gastrointestinal tract being the most common targets. aGvHD-mediated damage to these vital organs has been associated with increased morbidity and death.

HSCT is an effective treatment for aggressive leukemias and other hematological malignancies, often representing the only option for cure. However, some of its benefit, especially in the case of unrelated donor transplantation, is offset by a high rate of transplant-related mortality (TRM) stemming largely from severe aGvHD and infection.

About ORENCIA^®

ORENCIA^® is an immunomodulator that disrupts the continuous cycle of T-cell activation.

U.S. Indications/Usage and Important Safety Information for ORENCIA^® (abatacept)

Indications and Usage

Adult Rheumatoid Arthritis: ORENCIA^® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).

Polyarticular Juvenile Idiopathic Arthritis: ORENCIA^® (abatacept) is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).

Adult Psoriatic Arthritis: ORENCIA^® (abatacept) is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).

Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.

Important Safety Information for ORENCIA^® (abatacept)

Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) and serious infections (4.4% vs 0.8%) compared to patients treated with only TNF antagonists, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In post marketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations.

Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): In Study V, adult COPD patients treated with ORENCIA for RA developed adverse events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.

Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).

Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients.

Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

Please click here for Full Prescribing Information.

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.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Cautionary Statement Regarding Forward-Looking Statements

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 historical performance and 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 Orencia (abatacept) may not receive regulatory approval for the additional indication described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. It should also be noted that a Priority Review designation does not change the standards for FDA approval. 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, 2020, 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.

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WELIREG Approved for Adult Patients With VHL Disease Who Require Therapy for Associated Renal Cell Carcinoma, Central Nervous System Hemangioblastomas, or Pancreatic Neuroendocrine Tumors, Not Requiring Immediate Surgery

WELIREG Expands Merck’s Oncology Portfolio as the First and Only Systemic Therapy Approved for These Patients With VHL Disease

 

KENILWORTH, N.J. — (BUSINESS WIRE) — $MRK #MERCK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved WELIREG, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The recommended dose of WELIREG (40 mg tablets) is 120 mg once daily until disease progression or unacceptance toxicity. The approval is based on results from the open-label Study 004 trial (N=61), where the major efficacy endpoint was overall response rate (ORR) in patients with VHL-associated RCC.

WELIREG is the first HIF-2α inhibitor therapy approved in the U.S. As an inhibitor of HIF-2α, WELIREG reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth.

 

The WELIREG label contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of WELIREG and periodically throughout treatment. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with WELIREG. For more information, see “Selected Safety Information” below.

 

“VHL disease is a rare and serious condition. Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors,” said Dr. Eric Jonasch, principal investigator of Study 004 and professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The approval of WELIREG, which is based on data showing an overall response rate across three different types of VHL-associated tumors, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease.”

 

“WELIREG is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “Today’s approval of WELIREG is a significant milestone and is a testament to Merck’s commitment to bring forward innovative new treatment options for more patients.”

 

“The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,” said Dr. Ramaprasad Srinivasan, head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, National Cancer Institute (NCI), and principal investigator on the Cooperative Research and Development Agreement (CRADA) under which the NCI served as a site in Study 004. “In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with WELIREG experienced a reduction of their respective tumor size. The FDA’s approval of WELIREG marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors.”

 

Merck is working to optimize production of WELIREG to allow for a sustainable supply to meet anticipated U.S. demand. Commercial supply is expected to be available by early September.

 

Data Supporting the Approval

The approval was based on data from Study 004 (ClinicalTrials.gov, NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) localized to the kidney. Enrolled patients had other VHL-associated tumors, including CNS hemangioblastomas and pNET. CNS hemangioblastomas and pNET in these patients were diagnosed based on the presence of at least one measurable solid tumor in the brain/spine or pancreas, respectively, as defined by RECIST v1.1 and identified by an independent review committee (IRC). The study excluded patients with metastatic disease. Patients received WELIREG at a dose of 120 mg once daily until progression of disease or unacceptable toxicity. In Study 004, the median duration of exposure to WELIREG was 68 weeks (range, 8.4 to 104.7).

 

The study population characteristics were: median age of 41 years (range, 19 to 66), 3.3% age 65 or older; 53% male; 90% white, 3.3% Black or African American, 1.6% Asian, and 1.6% Native Hawaiian or other Pacific Islander; 82% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 16% had an ECOG PS of 1, and 1.6% had an ECOG PS of 2; and 84% had VHL type I disease. The median diameter of RCC target lesions per central IRC was 2.2 centimeters (range, 1 to 6.1). Median time from initial radiographic diagnosis of VHL-associated RCC tumors that led to enrollment on Study 004 to the time of treatment with WELIREG was 17.9 months (range, 2.8 to 96.7). Seventy-seven percent of patients had prior surgical procedures for RCC.

 

The major efficacy endpoint for the treatment of VHL-associated RCC was ORR measured by radiology assessment using RECIST v1.1 as assessed by IRC. Additional efficacy endpoints included duration of response (DoR) and time to response (TTR).

 

In patients with VHL-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62); all responses were partial responses. Median DoR had not yet been reached (range, 2.8+ to 22.3+ months); among responders, 56% (n=17/30) were still responding after at least 12 months. Median TTR was eight months (range, 2.7 to 19).

 

In patients with VHL-associated CNS hemangioblastomas (n=24), WELIREG showed an ORR of 63% (95% CI, 41-81), with a complete response rate of 4% (n=1) and a partial response rate of 58% (n=14). Median DoR had not yet been reached (range, 3.7+ to 22.3+ months); among responders, 73% (n=11/15) were still responding after at least 12 months. Median TTR was three months (range, 3 to 11).

 

In patients with VHL-associated pNET (n=12), WELIREG showed an ORR of 83% (95% CI, 52-98), with a complete response rate of 17% (n=2) and a partial response rate of 67% (n=8). Median DoR had not yet been reached (range, 10.8+ to 19.4+ months); among responders, 50% (n=5/10) were still responding after at least 12 months. Median TTR was eight months (range, 3 to 11).

 

Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment and central retinal vein occlusion (1 patient each). Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions that resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each).

 

Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients. Adverse reactions that required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache and influenza-like illness. Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction that required dose reduction was fatigue (7%).

 

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients treated with WELIREG were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%) and nausea (31%).

 

About Von Hippel-Lindau Disease

The incidence of von Hippel-Lindau (VHL) syndrome is estimated to be one in 36,000 individuals. This is a rare genetic disease with an estimated incidence of 10,000 people in the U.S. Patients with VHL disease are at risk for benign blood vessel tumors as well as some cancerous ones, including renal cell carcinoma.

 

WELIREG™ (belzutifan) Indication in the U.S.

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

 

Selected Safety Information

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

 

Anemia

WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.

 

Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

 

Transfuse patients as clinically indicated. For patients with hemoglobin <9g/dL, withhold WELIREG until Hb≥9g/dL, then resume at reduced dose or permanently discontinue depending on the severity of anemia. For life threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥9g/dL, then resume at a reduced dose or permanently discontinue.

 

The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG.

 

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. In Study 004, hypoxia occurred in 1.6% of patients. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, hypoxia occurred in 29% of patients; 16% were Grade 3 hypoxia.

 

Monitor oxygen saturation before initiation of and periodically throughout treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

 

Embryo-Fetal Toxicity

 

Based on findings in animal studies, WELIREG may cause fetal harm when administered to a pregnant woman.

 

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

 

Adverse Reactions

In Study 004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

 

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

 

The most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

 

In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

 

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

 

Coadministration of WELIREG with CYP3A4 substrates, including hormonal contraceptives, decreases concentration of CYP3A4 substrates, which may reduce the efficacy of these substrates. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

 

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

 

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

 

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

 

Based on findings in animals, WELIREG may impair fertility in males of reproductive potential and the reversibility of this effect is unknown.

 

Pediatric Use

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

 

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

 

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

 

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

 

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

 

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

# # #

Please see Prescribing Information, including information for the Boxed Warning, for WELIREG (belzutifan) at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf and Medication Guide for WELIREG at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf.

Contacts

Media Contacts:

Melissa Moody

(215) 407-3536

Justine Moore

(908) 740-6449

Investor Contacts:

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(908) 740-1037

Raychel Kruper

(908) 740-2107

Results from this study support the safety profile of oral islatravir PrEP regimen through 24 weeks versus placebo

 

KENILWORTH, N.J. — (BUSINESS WIRE) — $MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from a Phase 2a clinical trial evaluating the safety, tolerability and pharmacokinetics (PK) of six monthly oral doses, over 24 weeks, of islatravir, the company’s investigational nucleoside reverse transcriptase translocation inhibitor, versus placebo for pre-exposure prophylaxis (PrEP) of HIV-1 infection in adults at low-risk of contracting HIV-1. After 24 weeks, once-monthly oral islatravir was generally well tolerated versus placebo. Most adverse events (AEs) were mild and there were no serious drug-related AEs in people who received islatravir. The levels of islatravir in peripheral blood mononuclear cells (PBMCs) also remained above the pre-specified efficacy PK threshold for PrEP at both doses studied (60 mg and 120 mg) eight weeks after the last study dose. These data were shared as a late-breaking oral presentation during the virtual 11^th International AIDS Society Conference on HIV Science (IAS 2021) and are a follow-up to the interim analysis that was presented earlier this year at the virtual 2021 HIV Research for Prevention Conference (HIVR4P 2021).

“The 24-week analysis of investigational, once-monthly oral islatravir not only builds upon the PK data we have already seen, but also provides encouraging support for the safety and tolerability profile of this HIV-1 PrEP regimen,” said Dr. Joan Butterton, vice president, global clinical development, infectious diseases, Merck Research Laboratories. “As part of our commitment to understanding the potential for our HIV medicines in a broad range of patients, we focused on the enrollment of diverse patient populations at risk for HIV, including women, who have one of the highest unmet needs in HIV prevention.”

 

Islatravir is currently being evaluated across a variety of dosing regimens, for both the treatment of HIV-1 infection in combination with other antiretroviral agents and for the prevention of HIV-1 infection as a monotherapy. An overview of the islatravir treatment and prevention development program is available here, which includes our two Phase 3 IMPOWER trials evaluating islatravir as once-monthly oral PrEP across diverse populations of people who may benefit from additional HIV-1 prevention options.

 

Phase 2a Oral Study Results for Investigational Islatravir

In the ongoing Phase 2a (NCT04003103) randomized, double-blind, parallel assignment, placebo-controlled, multicenter trial in adults at low-risk for acquiring HIV-1 infection, participants were randomly assigned (2:2:1) to one of three oral once-monthly therapy groups: islatravir 60 mg, islatravir 120 mg or placebo. Participants received once monthly oral doses of islatravir or placebo over a 24-week blinded therapy period, followed by a 12-week blinded follow-up in all groups and a 32-week unblinded follow-up in the islatravir groups to characterize the terminal elimination phase. Outcome measures for safety, tolerability and PK will be analyzed through week 68.

 

Of the 242 randomized participants at this 24-week analysis, which concludes the dosing portion of the study, 92% (n=222/242) completed dosing and 8% (n=20/242) discontinued the study intervention before week 24. Less than 1% (n=2) of participants discontinued due to an AE. Of the total participants, 67.4% (n=163/242) were female, 52.9% (n=128/242) were white, 41.7% (n=101/242) were Black or African American and 14.9% (n=36/242) were Hispanic or Latino. Unblinded safety data showed that both doses of islatravir were generally well tolerated versus placebo over 24 weeks and most AEs were mild (73.5%). The most common AEs (occurring in >5% of participants) in the islatravir 60 mg, islatravir 120 mg and placebo groups respectively were headache (10.3% [n=10/97], 9.3% [n=9/97] and 4.2% [n=2/48]), diarrhea (5.2% [n=5/97], 5.2% [n=5/97] and 8.3% [n=4/48]) and nausea (5.2% [n=5/97]), 7.2% [n=7/97] and 4.2% [n=2/48]). There were no serious drug-related AEs in people who received islatravir. The study enrolled a population at low-risk for HIV infection as evidenced by no confirmed HIV infections occurring during the treatment period.

 

The PK analysis showed that trough concentrations (the lowest level between doses) of islatravir triphosphate in PBMCs following either 60 mg or 120 mg monthly doses continue to remain above the pre-specified PK threshold for HIV-1 prophylaxis of 0.05 pmol/10⁶ PBMCs and were sustained through eight weeks after the last dose of islatravir.

 

About Islatravir (MK-8591)

Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation in clinical trials for the treatment of HIV-1 infection in combination with other antiretrovirals, including the ILLUMINATE clinical trials program for once-daily treatment. Islatravir is also being studied for pre-exposure prophylaxis (PrEP) of HIV-1 infection as a single agent across a variety of formulations, including the IMPOWER clinical trials evaluating an oral once-monthly regimen.

 

Our Commitment to HIV

For more than 35 years, Merck has been committed to scientific research and discovery (R&D) in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to working hand-in-hand with our partners in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.

 

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

 

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

 

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

 

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Contacts

Media Contacts:

Melissa Moody

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Sienna Choi

(908) 873-4311

Investor Contacts:

Peter Dannenbaum

(908) 740-1037

Raychel Kruper

(908) 740-2107