Ensifentrine

With Europe's approval of Regeneron and Sanofi's Dupixent to treat chronic obstructive pulmonary disease, it becomes the first biologic option for the condition, which is the third-leading cause of death worldwide. After more than a decade with no treatment advances for chronic obstructive pulmonary disease (COPD), two have been approved by regulators on either side of the Atlantic within a week. Wednesday, the European Medicines Agency (EMA) signed off on Regeneron and Sanofi’s anti-inflammatory blockbuster Dupixent to treat COPD, which restricts airflow from the lungs and leaves patients struggling to breathe. This comes seven days after Verona Pharma earned a long-awaited nod from the FDA for Ohtuvayre, a dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes. “After more than a decade of limited treatment advancements for those living with uncontrolled COPD, we are now in a new era of disease management for patients and caregivers and welcome the addition of innovative, new treatments such as Dupixent to help manage this progressive and irreversible disease,” Tonya Winders, CEO of the Global Allergy & Airways Patient Platform, said in Sanofi and Regeneron's press release.  The nod for Dupixent—which becomes the first biologic and first targeted therapy to treat COPD—comes after U.S. regulators delayed their decision date on the drug by three months, from June 27 to Sept. 27. In doing so, the agency asked the companies to show more data from two trials. Regulators from the EMA have been satisfied with the phase 3 results, however. On the same day in May that the companies announced the delay in the U.S., Europe’s Committee for Medicinal Products for Human Use gave a thumbs-up to Dupixent. Dupixent has been approved as an add-on maintenance treatment with current therapies, which include inhaled corticosteroids, which reduce inflammation, and bronchodilators, which relax muscles in the lungs and widen the airways. Bronchodilators include long-acting beta agonists and long-acting muscarinic agonists. Meanwhile, the approval in the U.S. for Verona’s Ohtuvayre covers the treatment as an add-on drug or a monotherapy. Duxpixent was shown in the BOREAS and NOTUS trials to reduce moderate or severe exacerbations over 52 weeks of treatment by 30% and 34% respectively, compared to placebo. Those results compare to a 40% reduction in flare-ups in Verona’s two trials of after 24 weeks of treatment with Ohtuvayre. Analysts from GlobalData stressed the importance of Dupixent, as a biologic, ending the “current gap in the market for COPD." “Key opinion leaders (KOLs) interviewed by GlobalData have shared optimistic views on Dupixent, noting that its novel pathway presents anti-mucous effects, which is an additive value, supplementing its anti-eosinophil effects,” Asiyah Nawab, a pharma analyst at GlobalData, wrote. Three months ago, analysts at Evercore ISI projected that a COPD nod would add a potential sales boost of $3.5 billion annually for Dupixent, bringing its peak sales potential to $20 billion. Meanwhile, GlobalData pegs Dupixent’s sales to reach $23.6 billion by 2030.   Dupixent, which has been on the market for seven years, has garnered approvals to treat eczema and asthma along with rarer conditions such as rhinosinusitis, eosinophilic esophagitis and prurigo nodularis. Dupixent ranked No. 6 in worldwide sales last year with a global haul of $11.6 billion. The approval in Europe will open Dupixent’s use to more than 200,000 patients with COPD. The condition is the world’s third-leading cause of death.

Savara has announced positive late-stage results for its daily molgramostim nebuliser solution (molgramostim) treatment for a rare lung disease. The phase 3 IMPALA-2 clinical trial has been evaluating the efficacy and safety of molgramostim 300mcg administered once daily by inhalation versus placebo in adult patients living with autoimmune pulmonary alveolar proteinosis (aPAP). Chronic respiratory diseases were the third-leading cause of global deaths in 2019 and can be caused by infection, smoking tobacco, radon, asbestos or other forms of air pollution. Affecting around one in every 150,000 people in the US, aPAP is characterised by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation and innate immune deficiency. The trial met its primary endpoint after the therapy improved lung function in haemoglobin-adjusted percent predicted DLCO, a test that measures the diffusing capacity of the lung for carbon monoxide, achieving statistical significance compared to placebo at 24 weeks, which was maintained at 48 weeks. Bruce Trapnell, lead investigator of the trial, commented: “With convincing data from two large clinical trials, the evidence now clearly demonstrates molgramostim has the potential to be a safe and efficacious treatment option for [aPAP] patients.” Matt Pauls, chair and chief executive officer, Savara, said: “The strong efficacy data and favourable benefit-risk profile potentially positions molgramostim to be the first and only approved therapeutic for aPAP in the US and Europe.” The inhaled form of recombinant human granulocyte-macrophage colony-stimulating factor has already been granted Orphan Drug, Fast Track and Breakthrough Therapy designations by the US Food and Drug Administration (FDA), Orphan Drug Designation from the European Medicines Agency (EMA), as well as the Innovative Passport and Promising Innovative Medicine designations from the UK’s Medicines and Healthcare Products Regulatory Agency for the treatment of aPAP. Most recently, the FDA approved Verona Pharma’s Ohtuvayre (ensifentrine) as a maintenance treatment for adults living with chronic obstructive pulmonary disease (COPD), a common lung disease that affects more than 390 million people worldwide. Prior to this, in May, Sanofi and Regeneron’s Dupixent (dupilumab) was recommended by the EMA’s human medicines committee as an add-on maintenance treatment for COPD, following positive late-stage results from the NOTUS trial, which were presented at the 2024 American Thoracic Society International Conference.