Stephanie Fradette, head of Biogen’s neuromuscular development unit, commented, “While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of SPINRAZA established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety.” Biogen now plans to seek regulatory approval for this higher dose regimen. SPINRAZA, which generated $1.74 billion in sales for Biogen in 2023, is expected to see a decline in revenue, projected to reach $1.13 billion by 2030, due to shipment timing issues, increased competition, and pricing pressures outside the U.S.
Travere Secures FDA Approval for FILSPARI in IgAN After FSGS Setback
The FDA has granted full approval to Travere Therapeutics’ FILSPARI (sparsentan) for the treatment of primary IgA nephropathy (IgAN), upgrading its previous accelerated approval status. This decision broadens the drug’s use by eliminating the prior requirement of a urine protein-to-creatinine ratio (UPCR) above 1.5g/g, making it available to a wider range of patients at risk of disease progression.
The full approval comes with a boxed warning for potential hepatotoxicity and birth defects, leading to FILSPARI being distributed under a Risk Evaluation and Mitigation Strategies (REMS) program. The FDA requires kidney function monitoring before initiating treatment, with monthly tests during the first year and quarterly checks thereafter.
Stephanie Fradette, head of the neuromuscular development unit at Biogen, stated, “While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of SPINRAZA established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety.” In related news, Travere had previously sought approval for sparsentan for focal segmental glomerulosclerosis (FSGS) but faced additional data requests, leading the company to streamline its operations and focus on FILSPARI’s IgAN launch. Meanwhile, FILSPARI will compete with Novartis’s FABHALTA (iptacopan), atrasentan, and zigakibart, with recent advancements in these therapies adding to the dynamic treatment landscape for IgAN.
GSK’s NUCALA Achieves Success in COPD Phase III Trial
GSK’s asthma medication NUCALA (mepolizumab) has achieved its primary endpoint in a Phase III trial for chronic obstructive pulmonary disease (COPD). The MATINEE study demonstrated that adding NUCALA to inhaled maintenance therapy significantly reduced the annualized rate of moderate or severe COPD exacerbations compared to a placebo. While GSK has not released detailed data, they reported a “statistically significant and clinically meaningful reduction” in exacerbations over up to two years, with preliminary safety results aligning with NUCALA’s established profile.
The late-stage trial, involving 806 patients aged 40 and older, was conducted globally across the Americas, Europe, and Asia. NUCALA was administered as a subcutaneous injection every four weeks in addition to standard therapy. GSK plans to submit regulatory filings for NUCALA’s COPD indication in the EU and Canada by 2025, although a specific timeline was not confirmed.
GSK spokesperson said, “We are pleased with the results of the MATINEE study and are committed to advancing NUCALA as a treatment option for COPD. Our next steps include further data analysis to fully understand the benefits and safety of NUCALA in this new indication.” NUCALA, which generated £1.6 billion ($2.1 billion) in revenue in 2023, is forecasted to peak at $2.35 billion in sales by 2026. Meanwhile, Sanofi’s DUPIXENT (dupilumab) recently became the first targeted therapy approved for adults with uncontrolled COPD, underscoring the growing competition in this therapeutic area.
Summit’s NSCLC Success Against KEYTRUDA Draws Caution Over China-Only Data
Summit Therapeutics has unveiled promising data from its Phase III HARMONi-2 trial, indicating that its investigational bispecific antibody, ivonescimab, significantly outperforms Merck’s KEYTRUDA (pembrolizumab) in treating advanced non-small cell lung cancer (NSCLC). Ivonescimab showed a 49% reduction in the risk of disease progression or death compared to KEYTRUDA, with a median progression-free survival (PFS) of 11.14 months versus 5.82 months for KEYTRUDA. The results, presented at the International Association for the Study of Lung Cancer’s 2024 World Conference on Lung Cancer, are statistically significant with a p-value of less than 0.0001.
Despite these impressive results, analysts urge caution. BMO Capital Markets’ Evan Seigerman emphasized that while ivonescimab shows strong performance, it is “not yet the KEYTRUDA slayer.” He pointed out that the trial was conducted exclusively in China, which may limit the generalizability of the findings to other populations. Additionally, Summit has yet to release overall survival (OS) data, which is crucial for treatment decisions.
Summit CEO Maky Zanganeh expressed optimism, stating, “HARMONi-2 clearly demonstrates that ivonescimab has the potential to be the next generation in PD-1 directed immunotherapy.” Zanganeh also highlighted the potential for ivonescimab to extend beyond lung cancer to other tumors. Summit plans to advance ivonescimab into the multi-regional HARMONi-7 study, set to begin in early 2025, with the goal of securing broader regulatory approval. However, analysts like Truist Securities’ Srikripa Devarakonda caution that the current regional focus of the study may impact U.S. approval timelines, given the need for additional global data.
FDA Lifts Partial Hold on RZ358 for Congenital Hyperinsulinism, U.S. Phase III Study to Continue
Rezolute, Inc. announced a significant regulatory milestone: the FDA has lifted the partial clinical holds on RZ358 (ersodetug), a novel therapy for treating hypoglycemia associated with congenital hyperinsulinism (HI). This decision clears the way for Rezolute to move forward with the U.S. component of the global Phase III sunRIZE study, which is a multi-center, double-blind, randomized, placebo-controlled trial assessing the safety and efficacy of ersodetug.
With the partial holds removed, Rezolute will begin preparations to enroll U.S. participants in early 2025, aiming to include them in the ongoing sunRIZE study. The company expects to announce topline results from the study in the latter half of 2025. The FDA’s decision also allows the inclusion of participants as young as three months old and confirms that the liver toxicity observed in preclinical studies with Sprague Dawley rats is considered strain-specific and not applicable to humans.
Rezolute CEO and Founder Nevan Charles Elam expressed enthusiasm about the development, stating, “We are delighted that the FDA has completely removed the partial clinical holds and are allowing us to proceed in the U.S. at all doses and in participants as young as three months of age. The FDA’s conclusion that the liver toxicity observed in rats is likely strain-specific is particularly encouraging.” Elam also highlighted the recent FDA clearance for a separate Phase III study in tumor-associated HI, positioning Rezolute to advance ersodetug in two significant Phase III programs both in the U.S. and globally.
