Dupilumab

On Tuesday, GSK won approval for a drug the company predicts can reach up to $4 billion in peak annual sales.The Food and Drug Administration cleared GSKs depemokimab, which will have the brand name Exdensur, as an add-on maintenance treatment for those aged 12 years and older with severe eosinophilic asthma, becoming the first biologic approved with twice-yearly dosing.The approval follows the recent backing of Exdensur by the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency. The CHMP gave a positive recommendation to the drug across two indications: as an add-on maintenance treatment for severe asthma with type 2 inflammation, as well as for adults with chronic rhinosinusitis with nasal polyps that is inadequately controlled. The FDA has not approved Exdensur in the latter indication.The FDA clearance is supported by data from two late-stage studies, titled SWIFT-1 and SWIFT-2, which found that Exdensur, when added to standard treatment and compared to a placebo, demonstrated a reduction in asthma attacks and hospitalizations. The drug is an ultra-long-acting biologic that targets IL-5, a protein thought to drive Type 2 inflammation.GSK is entering a market already stacked with several competitors, including Sanofi and Regenerons Dupixent, AstraZenecas Fasenra, and the more recently approved Tezspire from AstraZeneca and Amgen. Yet GSK has maintained that its IL-5 inhibitor could become a blockbuster, as well as a new standard of care for those with severe asthma.About 2 million Americans live with severe asthma, with half experiencing attacks that could lead to hospitalizations. Despite the availability of effective biologic drugs, less than 30% of eligible patients can receive these treatments. And according to GSK, 65% of new biologic patients discontinue therapy within the first year.Approved medicines to treat severe asthma often come with long, multiple dosing schedules that could be difficult to adhere to and could lead to severe outcomes if not maintained.Physicians in the US now have the option to provide sustained protection from exacerbations for patients living with severe asthma with an eosinophilic phenotype in just two doses a year, said Kaivan Khavandi, global head of respiratory, immunology & inflammation R&D, in a statement. Exdensur could redefine patient care and further establish the use of biologics for those who continue to experience exacerbations despite treatment.In an email to BioPharma Dive, a GSK spokesperson said that the company will disclose the drug's price once it launches in January. The company is in “active dialogue“ with the FDA regarding a future clearance in rhinusitis.Editor's note: This story has been updated with comments from a GSK spokesperson. '

Nektar Therapeutics blamed the missed endpoint on four patients who were enrolled in the trial in error, all of whom “did not meet major study eligibility criteria at baseline.” \n Nektar Therapeutics is planning to bring its interleukin-2-targeting drug candidate into a phase 3 trial for severe alopecia areata, even after the asset narrowly missed the main goal of a midstage trial.The biotech said the miss occurred because four of the patients were enrolled erroneously, all of whom “did not meet major study eligibility criteria at baseline,” according to a Dec. 16 company release.When those patients were excluded, Nektar’s candidate rezpegaldesleukin did meet the study’s goal, significantly reducing the severity of scalp hair loss by about 30% compared to 6% for placebo, the biotech said.“These four cases were adjudicated by three medical monitors that were blinded to this study, who all determined in unison that these four patients should never have been enrolled to the trial,” Mary Tagliaferri, M.D., Nektar’s chief medical officer, said in a Dec. 16 conference call about the results. “We then did this analysis and clearly demonstrated a very clear efficacy meeting our target product profile.”The phase 2 Rezolve AA trial enrolled a total of 92 patients, including the four who were later excluded, and randomized them to receive 18 milligrams per kilogram of rezpeg, 24 mg per kg of rezpeg or placebo. One of the inappropriately enrolled patients was in the placebo arm and had been diagnosed with alopecia areata less than six months before entering the study, a period when the autoimmune disease is usually unstable.“When patients don\'t have stable disease, you can have a higher placebo rate” and spontaneous regrowth of hair, David Rosmarin, M.D., a dermatologist at the Indiana University School of Medicine, said on the conference call. Excluding such patients “is routine in all alopecia areata studies” to ensure that hair regrowth seen in the trial is being caused by treatment.In a larger phase 3 trial, Rosmarin added, a patient with an abnormally large placebo effect “would be a blip on the screen.”Analysts from William Blair agreed that rezpeg “exhibits clinical activity in alopecia areata,” according to a Dec. 16 note, while adding the efficacy seen so far is lower than that seen in low-dose JAK inhibitors, three of which are approved for severe alopecia areata.However, Rosmarin and two other dermatologists on the call noted that patients can be uncomfortable with JAK inhibitors due to their black box warnings and requirements for consistent monitoring.“There are a lot of dermatologists and patients who are scared to use JAK inhibitors,” Jonathan Silverberg, M.D., Ph.D., a dermatologist at the George Washington University School of Medicine and Health Sciences, said on the call. “The field sorely needs a clean biologic without the laboratory monitoring or boxed warnings.” Rezpeg commonly caused injection-site reactions like redness or swelling, 87% of which were mild and none of which led to a discontinuation, Nektar CMO Tagliaferri said during the call. One patient who received rezpeg discontinued treatment due to an adverse event, and, overall, rezpeg led to no increased risk of major cardiovascular events, thrombosis, acne or oral herpes, she added.Rezpeg is designed to target interleukin-2 receptors in order to boost the activity of regulatory T cells (Tregs), a rare population of immune cells that calm the self-destructive immune response typical of autoimmune diseases like alopecia. The discoverers of Tregs were awarded the Nobel Prize in Physiology or Medicine this October, and numerous biotechs are striving to turn the potent cells into new therapies.Nektar is also testing rezpeg in phase 2 trials in atopic dermatitis and Type 1 diabetes. The biotech announced in June that the molecule had notched a win in the atopic dermatitis trial, though with lower efficacy than Regeneron and Sanofi’s blockbuster Dupixent.Rezpeg has a dramatic history—it used to be part of a collaboration with Eli Lilly before the pharma handed it back to Nektar in 2023 after growing unimpressed with the candidate’s efficacy. However, Nektar accused the drugmaker of botching its analysis of the phase 1b data from patients with atopic dermatitis and psoriasis in a manner that misrepresented rezpeg’s potential.Nektar chose to sue Lilly in August 2023, and Lilly countersued in March 2024. As of now, the case is still making its way through the district court of Northern California.