BeiGene Receives FDA Accelerated Approval for BRUKINSA in Relapsed/Refractory Follicular Lymphoma

BeiGene, Ltd., has declared that the FDA has provided accelerated approval for BRUKINSA® (zanubrutinib) to be used in treating adult patients with relapsed or refractory (R/R) follicular lymphoma (FL), when used alongside the anti-CD20 monoclonal antibody obinutuzumab, following two or more rounds of systemic therapy. This approval is granted under accelerated approval conditions, which consider the response rate and the lasting effectiveness of the response. This marks the fifth approved use of BRUKINSA for B-cell malignancies in the United States.

Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer for Hematology at BeiGene, highlighted the significance of the accelerated approval for BRUKINSA, marking a pivotal step forward. This approval offers the first and only BTK inhibitor therapy for individuals in the U.S. diagnosed with follicular lymphoma who have not responded to initial treatments or have faced relapses. Dr. Mobasher emphasized that BRUKINSA stands out as the sole BTK inhibitor demonstrating effectiveness against this particular type of cancer. Furthermore, it now holds the most extensive range of approved uses among medications in its class globally, encompassing five oncology indications. This achievement underscores the distinct clinical profile of BRUKINSA and BeiGene’s ongoing dedication to making this vital treatment option available to patients worldwide.

Through the accelerated approval program, BRUKINSA received FDA approval for treating Relapsed or Refractory (R/R) Follicular Lymphoma. This approval was based on the overall response rate (ORR) observed in the ROSEWOOD trial (NCT03332017), as evaluated by an independent review committee (IRC). Continued approval for this specific use will depend on confirming and describing the clinical benefits observed in the ongoing MAHOGANY trial (NCT05100862). Additionally, the FDA has granted Fast Track Designation and Orphan Drug Designation for the R/R Follicular Lymphoma application.

BRUKINSA has received approval in 70 markets, such as the U.S., EU, Great Britain, Canada, Australia, China, South Korea, and Switzerland, for specific uses. Additionally, it is undergoing expansion for further applications worldwide. The worldwide development plan for BRUKINSA involves over 5,000 participants enrolled in 29 countries and regions up to now.

GSK Reveals Encouraging Outcomes from DREAMM-8 Phase III Study for Blenrep in Relapsed/Refractory Multiple Myeloma

GSK plc has reported positive initial findings from the DREAMM-8 phase III comparative study, which examined Blenrep (belantamab mafodotin) alongside pomalidomide plus dexamethasone (PomDex) versus the standard treatment of bortezomib plus PomDex, for second-line and subsequent therapies in patients with relapsed or refractory multiple myeloma. The study successfully achieved its main goal of extending progression-free survival (PFS) as per the predetermined interim analysis and was prematurely unmasked following a recommendation by an Independent Data Monitoring Committee (IDMC).

The combination of belantamab mafodotin notably increased the duration before disease progression or death compared to the standard combination treatment. Additionally, there was a promising trend towards improved overall survival (OS) with the use of Blenrep in this analysis. The study is ongoing to monitor overall survival. The safety and how well the body tolerated the belantamab mafodotin regimen were generally in line with what is already known about the safety of the individual drugs involved.

Hesham Abdullah, GSK’s Senior Vice President and Global Head of Oncology Research and Development, commented that the findings from both the DREAMM-7 and DREAMM-8 trials present compelling clinical proof of belantamab mafodotin’s strong effectiveness when used alongside standard treatment regimens. The next step involves sharing these results with regulatory authorities. If granted approval, these combinations could potentially redefine how relapsed or refractory multiple myeloma is treated and elevate the standard of care. This development is particularly promising for patients, considering the significant need for treatments that are both effective and easy to administer, and that operate through diverse mechanisms of action.

DREAMM-8 marks the second phase III trial, comparing belantamab mafodotin combinations for second-line and later treatment of multiple myeloma, to announce positive outcomes. The favorable results of DREAMM-7, another phase III trial comparing belantamab mafodotin with bortezomib and dexamethasone (BorDex) against daratumumab plus BorDex in the same treatment setting, were revealed at the American Society of Clinical Oncology (ASCO) Plenary Series on February 6, 2024. Detailed findings from DREAMM-8 will be presented at an upcoming medical conference and shared with regulatory bodies.

FDA Approves Sandoz’s Groundbreaking Denosumab Biosimilars

Sandoz, the leading worldwide provider of generic and biosimilar medications, revealed that the FDA has approved Wyost® (denosumab-bbdz) and Jubbonti® (denosumab-bbdz). These are the initial FDA-approved biosimilars of denosumab, authorized to treat all conditions for which the original medications are used.

Keren Haruvi, President of Sandoz North America, expressed: “Sandoz has secured the initial FDA authorization for biosimilars designed for denosumab, a treatment addressing both primary and secondary bone loss, such as osteoporosis, alongside skeletal events related to cancer. These conditions significantly impact patients’ quality of life. I am pleased that Sandoz remains at the forefront of providing crucial medicines to those who require them the most.”

The FDA’s authorization is grounded in thorough clinical research and is supplemented by labeling containing safety precautions. Additionally, the approval of Jubbonti entails the endorsement of Sandoz’s Jubbonti® Risk Evaluation and Mitigation Strategy (REMS) initiative. This program is crafted to educate healthcare providers and patients about the potential risk of severe hypocalcemia linked with Jubbonti® in individuals with advanced chronic kidney disease, including those undergoing dialysis. Both Wyost® and Jubbonti® share identical characteristics with their respective reference medications, including dosage form, administration route, dosing schedule, and presentation. Consequently, they are sanctioned as interchangeable with the reference drugs for all prescribed uses.

Due to the continuing patent disputes regarding these items, Sandoz will refrain from discussing the expected release schedule or any other specifics of the launch at this moment.

Terns Pharmaceuticals Receives Orphan Drug Designation for TERN-701 in Chronic Myeloid Leukemia

March 11, 2024, marked a monumental day for Terns Pharmaceuticals, Inc. (“Terns”), as the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to its therapy, TERN-701 for the treatment of Chronic Myeloid Leukemia (CML). This designation not only underscores the significance of TERN-701 but also highlights the urgent need for innovative therapies in combating this challenging disease.

TERN-701, an allosteric BCR-ABL tyrosine kinase inhibitor (TKI), represents a groundbreaking advancement in the field of oncology. Developed internally by Terns, this promising compound has entered Phase 1 clinical development, positioning it at the forefront of cutting-edge research. The anticipation surrounding TERN-701 is palpable, with interim data from initial dose escalation cohorts slated for release in the latter half of 2024.

“Chronic Myeloid Leukemia is a serious leukemia that requires chronic, life-long treatment,” said Emil Kuriakose, MD, chief medical officer of Terns. “Allosteric TKIs are a novel class of inhibitors that are highly selective and have demonstrated significantly improved clinical efficacy, safety and tolerability compared to prior generation active-site TKIs. Orphan drug designation for TERN-701 underscores the FDA’s recognition of the unmet need for people living with Chronic Myeloid Leukemia and Terns’ commitment to developing new treatment options.”

The granting of Orphan Drug Designation by the FDA is a testament to the potential of TERN-701 to address the unmet medical needs of Chronic Myeloid Leukemia patients. By conferring this status, the FDA acknowledges the rarity and severity of Chronic Myeloid Leukemia, emphasizing the importance of accelerating the development of novel therapeutic interventions.

This significant milestone not only validates Terns’ dedication to pioneering research but also offers hope to individuals battling Chronic Myeloid Leukemia. The journey toward regulatory approval for TERN-701 represents a beacon of progress in the fight against hematologic malignancies, marking a significant step forward in improving patient outcomes and quality of life.

Overall, the FDA’s Orphan Drug Designation for TERN-701 heralds a new era in the treatment of Chronic Myeloid Leukemia, underscoring its potential to revolutionize the standard of care and cementing its status as a transformative breakthrough in oncology.

Wegovy® Approved in the US for Reducing Cardiovascular Risk in Overweight or Obese Individuals with Established Cardiovascular Disease

On 8 March 2024, Novo Nordisk announced the US Food and Drug Administration (FDA) approval of a label expansion for its therapy, Wegovy®. This milestone was achieved through a supplemental New Drug Application (sNDA), extending Wegovy®’s indication to encompass the mitigation of major adverse cardiovascular events (MACE) in adults grappling with overweight or obesity and diagnosed with established cardiovascular disease (CVD).

The FDA’s nod for this label expansion signifies a significant advancement in addressing the multifaceted challenges posed by cardiovascular health in individuals with overweight or obesity and concurrent CVD. This regulatory milestone underscores Novo Nordisk’s commitment to enhancing patient outcomes through innovative therapeutic solutions, offering renewed hope for those navigating the complexities of managing cardiovascular risk factors alongside their weight.

The green light for this approval stems from the findings of the SELECT cardiovascular outcomes trial. This landmark study showcased that Wegovy® achieved a noteworthy 20% reduction in the risk of major adverse cardiovascular events (MACE) when administered alongside standard of care, compared to a placebo. However, despite this compelling evidence, the precise mechanism through which Wegovy® mitigates cardiovascular risk remains to be fully elucidated. This underscores the complexity of cardiovascular health and highlights the ongoing need for further research to unravel the intricacies of Wegovy®’s impact on cardiovascular outcomes.

The SELECT data were presented at the American Heart Association (AHA) annual meeting in November 2023 and published in the New England Journal of Medicine (NEJM).

The results derived from the SELECT trial also unveiled that the risk reductions in major adverse cardiovascular events (MACE) persisted over a span of up to five years, irrespective of various baseline factors such as age, sex, race, ethnicity, body mass index (BMI), and the degree of renal function impairment. Moreover, the updated label incorporates compelling data from SELECT indicating a 15% reduction in the risk of cardiovascular death and a 19% reduction in the risk of all-cause mortality, both relative to the placebo group. Furthermore, the label now encompasses additional clinical insights gleaned from the SELECT trial, further enhancing the comprehensive understanding of Wegovy®’s cardiovascular effects and its potential benefits for patients.

“We are very pleased that Wegovy® is now approved in the US as the first therapy to help people manage their weight and reduce cardiovascular risks. This approval is an important milestone for people living with obesity and cardiovascular disease, as the SELECT data demonstrated that Wegovy® has the potential to prolong lives by addressing some of the leading causes of preventable deaths by reducing the risks of cardiovascular events.”

Martin Holst Lange, executive vice president and head of Development at Novo Nordisk

Novo Nordisk has initiated the process of seeking a label expansion for Wegovy® in the European Union (EU), marking a significant step towards broadening its availability to patients beyond the US market. Anticipation surrounds the decision, which is slated for 2024, as stakeholders eagerly await the potential approval and subsequent impact on the management of obesity-related cardiovascular risk in European populations. This expansion initiative underscores Novo Nordisk’s commitment to addressing global health challenges and advancing access to innovative therapeutic options for individuals affected with overweight or obesity and its associated complications.

Managing obesity is a complex and enduring endeavor, as it is classified as a chronic condition, necessitating ongoing care. The ramifications of obesity are profound, extending to various serious health implications and even a reduction in life expectancy. Among the myriad of complications linked to obesity are type 2 diabetes, chronic kidney disease, non-alcoholic fatty liver disease, cancer, and an elevated susceptibility to cardiovascular diseases (CVD), encompassing heart attacks and strokes. 

Additionally, individuals with obesity often contend with elevated levels of blood sugar, cholesterol, blood pressure, and inflammatory markers, further underscoring the multifaceted nature of this health challenge. Addressing obesity comprehensively requires a holistic approach that acknowledges its far-reaching impact on overall well-being and emphasizes the importance of sustained management strategies.

Travere Therapeutics Submits sNDA to FDA for Full Approval of FILSPARI® (sparsentan) in IgA Nephropathy (IgAN)

On March 11, 2024, Travere Therapeutics, Inc. (Nasdaq: TVTX) made a significant announcement, revealing the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA). This application aims to transition the current accelerated approval status of FILSPARI® (sparsentan) in IgA Nephropathy (IgAN) to full approval. Originally, in February 2023, FILSPARI received accelerated approval from the FDA, marking a milestone as the inaugural non-immunosuppressive treatment specifically designed to target glomerular injury in the kidney, thereby reducing proteinuria in adult patients with primary IgA Nephropathy who are susceptible to rapid disease progression.

The basis for this sNDA rests upon the comprehensive 2-year confirmatory findings from the Phase 3 PROTECT Study. This study stands out as the sole head-to-head investigation conducted in the context of IgAN, comparing FILSPARI against an active comparator. The culmination of these results provides robust evidence supporting the efficacy and safety of FILSPARI in treating IgAN, thereby bolstering the case for its transition to full FDA approval.

“Since being introduced under accelerated approval, FILSPARI has positively impacted the lives of many people living with IgAN. The submission of the sNDA is an important step toward potentially gaining full approval in IgAN in support of reaching more people living with this devastating rare kidney disease. FILSPARI is at the forefront of emerging new treatment options providing hope for a delay in kidney transplant or dialysis. The results from the pivotal Phase 3 PROTECT Study show that by directly targeting glomerular injury in the kidney with FILSPARI, patients can achieve sustained proteinuria reduction and long-term kidney function preservation. We look forward to working with the FDA throughout the upcoming review process.”

Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics.

FILSPARI represents a breakthrough in IgA Nephropathy treatment as a once-daily oral medication directly addressing glomerular injury in the kidney. It achieves this by inhibiting two pivotal pathways—endothelin-1 and angiotensin II—associated with IgA Nephropathy disease progression. Notably, FILSPARI stands out as the premier non-immunosuppressive therapy endorsed for managing this rare kidney ailment. The submission of the sNDA is underpinned by compelling data from the Phase 3 PROTECT Study, showcasing FILSPARI’s efficacy in preserving long-term kidney function. Furthermore, the study demonstrates FILSPARI’s ability to significantly reduce proteinuria and deliver a clinically significant difference in eGFR slope compared to an active comparator, marking a significant advancement in IgA Nephropathy treatment.

Upon submission, the FDA has a 60-day window to assess the application’s eligibility for review. Anticipating this process, the Company foresees receiving notification regarding the acceptance for review of the sNDA submission, along with the projected timeline for sNDA review, from the FDA during the second quarter of 2024. In tandem with the sNDA submission to the FDA, the Company, alongside its European commercial partner CSL Vifor, recently unveiled that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the conditional marketing authorization (CMA) for sparsentan in treating IgA Nephropathy (IgAN) within Europe. The decision from the European Commission is slated for the second quarter of 2024. If granted approval, sparsentan stands to receive CMA across all member states of the European Union, as well as in Iceland, Liechtenstein, and Norway.

IgA Nephropathy (IgAN), known colloquially as Berger’s disease, presents a significant challenge as a rare and progressive kidney disorder marked by the accumulation of immunoglobulin A (IgA) within the kidneys. This accumulation compromises kidney function over time. IgAN stands as the predominant form of primary glomerulonephritis globally and ranks as a primary contributor to kidney failure stemming from glomerular ailments. Its impact is profound, with estimates suggesting it afflicts up to 150,000 individuals in the U.S. alone. Furthermore, IgAN stands as one of the most prevalent glomerular diseases not only in Europe and Japan but also worldwide. The burden of IgAN on affected individuals, families, and healthcare systems is substantial. Given its chronic and progressive nature, managing IgAN demands continuous care, often involving a multidisciplinary approach and, in many cases, necessitating invasive treatments such as dialysis or kidney transplantation. 

The submission of the Supplemental New Drug Application (sNDA) for FILSPARI® (sparsentan) represents a pivotal step in mitigating the burden of IgAN. FILSPARI, with its unique mechanism of action targeting glomerular injury, offers a promising avenue for effectively managing IgAN and potentially slowing its progression. By providing patients with a non-immunosuppressive treatment option, FILSPARI has the potential to reduce the reliance on traditional therapies with significant side effects. If approved, FILSPARI could significantly enhance the treatment landscape for IgA Nephropathy, offering hope to patients and clinicians alike in the quest to alleviate the burden of this debilitating kidney disease.