Anifrolumab-FNIA

While AZ has undergone an audit of its Saphnelo datasets to regain the agency’s trust, GSK faces a more daunting challenge: proving that Exdensur actually works in CRSwNP. The FDA is providing more insight into the rejections it recently handed two pharma giants, publishing the complete response letters (CRLs) sent to AstraZeneca and GSK that highlight shortfalls in the data included in their application packages.In a scathing rebuke (PDF) to AstraZeneca, the FDA cited “critical data quality issues that affect key analyses, including the primary endpoint” within a dataset for Saphnelo (anifrolumab) for the drug’s proposed use in systemic lupus erythematosus (SLE). Separately, the agency rejected (PDF) GSK’s Exdensur (depemokimab) for chronic rhinosinusitis with nasal polyps (CRSwNP), ruling that the clinical data failed to provide “adequate evidence” of efficacy, casting doubts on the drug’s potential expansion in that use.The publication of the rejection letters underscores the FDA’s promise of “radical transparency” regarding its drug review process. While AZ has undergone an audit of its Saphnelo datasets to regain the agency’s trust, GSK faces a more daunting challenge: proving that Exdensur actually works in CRSwNP.For AZ, the CRL was issued on Oct. 10, 2025, according to the FDA’s database. But the company didn’t disclose it until Feb. 3, 2026. At that time, the company said it had submitted the information requested by the FDA in the CRL, and that a decision on the updated application was expected in the first half of this year. AZ’s initial submission was based on an interim analysis of the phase 3 Tulip-SC trial, which showed a reduction in disease activity for subcutaneous Saphnelo versus placebo as measured using the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at week 52. However, in the CRL, the FDA flagged that AZ had submitted a “corrected” dataset for the study late in the review cycle after initially making “errors” in the application.As a result, the FDA asked AZ to provide, among other things, a “corrected interim clinical study report” and corrected raw datasets for both the interim and final analyses, presented in formats standard for regulatory reviews. Additionally, the FDA asked the company to “provide a detailed discussion of what led to the errors in the locked database being found,” as well as “a subject-level listing of all the changes in all the datasets along with the reason for each change.”Two months following the FDA’s rejection, European regulators authorized subcutaneous Saphnelo in SLE. This is not the first time that AZ has found itself dealing with data quality issues in a drug application for a kidney disease treatment. Back in 2021, AZ’s then-partner FibroGen filed for an FDA approval but then admitted to manipulating the safety data of roxadustat in chronic kidney disease-related anemia, data that the two firms unveiled to much fanfare in 2019.Roxadustat has since been rejected by the FDA, and AZ exited the collaboration in the U.S. in 2024. Efficacy questions for GSK Meanwhile, GSK faces a different hurdle for Exdensur, as the FDA has asked for “new evidence” that can demonstrate a treatment effect of greater magnitude to prove that the antibody drug provides a “statistically persuasive and clinically meaningful” benefit to CRSwNP patients. In its CRL to GSK, the FDA acknowledged that the co-primary endpoints of the Anchor-1 and -2 trials were met, showing statistically significant improvements for Exdensur versus placebo on nasal polyp scores and nasal obstruction scores. However, on the nasal obstruction score measure, the FDA found the outcomes were “not robust to sensitivity analyses for missing data and handling of intercurrent events.” The FDA views results from the patient-reported endpoint “especially important for assessing benefit-risk because they are a direct reflection of the clinically meaningful effects for patients.”The magnitude of the effects for both primary endpoints was “numerically small,” so the FDA questioned their clinical meaningfulness.The agency’s review team also looked at secondary endpoints, including additional patient-reported symptom scores, the need for nasal sinus or polyp surgery, and oral corticosteroid use. However, because of the statistical design of the studies, none of those endpoints met statistical significance, despite trends favoring Exdensur.The FDA went on further to suggest that a higher dose than the 100 mg selected by GSK “may provide a greater treatment effect,” faulting GSK for not running phase 2 dose-ranging trials specifically in CRSwNP.To tip the review balance further against GSK, the FDA said the every-half-year dosing—a long-acting feature that GSK has touted—means that non-responders would either have to wait a long time to switch to another drug, or risk any issues from taking two biologic therapies while Exdensur is still present in their bodies. “Given the small effect size for depemokimab with lack of robustness on tipping point analysis, the benefit-risk in the setting of a six-month duration of action is not favorable,” the FDA concluded. While the FDA declined to approve Exdensur in CRSwNP, the agency approved the long-acting IL-5 agent as an add-on maintenance treatment for severe asthma with an eosinophilic phenotype. The drug is approved in the EU for both indications.“We remain confident in the benefit Exdensur could bring for patients with CRSwNP and are continuing discussions with the FDA,” a GSK spokesperson told Fierce Pharma. GSK’s focus in the U.S. is on severe asthma, which affects about two million Americans with more than half uncontrolled on current therapy, as well as chronic obstructive pulmonary disease (COPD), the spokesperson added.Exdensur is a key element of GSK's plan to reach more than 40 billion pounds sterling in annual revenue by 2031, a task that has recently fallen on the shoulders of new CEO Luke Miels. In a more important indication than CRSwNP, GSK is testing Exdensur in three phase 3 trials in COPD.

Johnson & Johnson (J&J; NYSE: JNJ) announced receipt of Fast Track designation from the US FDA for nipocalimab, an investigational anti-neonatal Fc receptor (FcRn) monoclonal antibody, for the treatment of adults with systemic lupus erythematosus (SLE). This is the fifth FDA Fast Track designation for nipocalimab, which Johnson & Johnson acquired through its USD 6.5 billion purchase of Momenta Pharmaceuticals in October 2020. FDA Fast Track designation is available to therapies intended to treat serious conditions where evidence suggests the drug may address an unmet medical need. The procedural benefits include more frequent interactions with the agency during development, eligibility for rolling submission of a Biologics License Application (BLA), and potential qualification for Accelerated Approval or Priority Review at the time of filing. The designation rests on data from the Phase II JASMINE study (NCT04882878), a 52-week, randomized, double-blind, placebo-controlled, dose-ranging trial enrolling 228 adults with active SLE. According to Johnson & Johnson, the study met its primary endpoint and multiple secondary and exploratory endpoints, demonstrating reduction in lupus disease activity and steroid-sparing potential. Nipocalimab is the only FcRn blocker to have shown reduction in SLE disease activity in a controlled Phase II setting. Following these results, Johnson & Johnson initiated enrollment in the Phase III GARDENIA study (NCT07438496) of adults with active SLE. Nipocalimab functions by binding FcRn with high affinity, blocking IgG recycling and thereby reducing circulating pathogenic immunoglobulin G (IgG) autoantibodies while preserving other immune functions. J&J is developing the molecule across rheumatologic, rare autoantibody, and maternal-fetal indications. Active or completed trials include Phase III studies in generalized myasthenia gravis (gMG), where FDA granted Priority Review in Q4 2024, and in fetal and neonatal alloimmune thrombocytopenia (FNAIT). Nipocalimab also holds Breakthrough Therapy designations for hemolytic disease of the fetus and newborn (HDFN) and Sjögren’s disease. SLE is a chronic autoimmune disease affecting an estimated 3 to 5 million people worldwide, with disproportionate prevalence among women of reproductive age. The disease drives inflammation across multiple organ systems, including the kidneys, skin, joints, and central nervous system, and carries a risk of irreversible organ damage compounded by long-term glucocorticoid dependence. Only two biologic therapies have received FDA approval for SLE: belimumab (GSK, approved 2011), a B-lymphocyte stimulator inhibitor, and anifrolumab (AstraZeneca, branded Saphnelo, approved 2021), a type I interferon receptor antibody. No novel molecular entity for SLE has been approved since anifrolumab. The FcRn target class is crowded. Argenx markets efgartigimod (Vyvgart) for gMG and is studying it in lupus nephritis in the Phase II/III ALKIVIA trial (NCT05523570). UCB’s rozanolixizumab and Immunovant’s batoclimab are both in Phase III for gMG and other IgG-mediated conditions, though neither has disclosed an active SLE program. Nipocalimab differs from efgartigimod in modality: it is a full-length monoclonal antibody rather than an engineered Fc fragment, and J&J characterizes it as “immunoselective”, a term denoting its design to lower pathogenic IgG without broadly suppressing other immunoglobulin classes or complement-dependent functions. Whether this translates into a differentiated clinical profile in SLE remains to be established in Phase III data.