July immunology roundup: new therapies, trial insights, and regulatory milestones

Approvals

• FDA approves new low-IgA immunoglobulin therapy for primary immunodeficiency

The FDA approved a new ready-to-use liquid immunoglobulin therapy for individuals aged two and older with primary immunodeficiency (PI).¹ This treatment is the only liquid formulation available with low immunoglobulin A (IgA) content; less than or equal to 2 µg/mL in a 10% solution, making it a suitable option for patients with anti-IgA antibodies who are at higher risk of adverse reactions. Its ready-to-infuse format eliminates the need for reconstitution, offering greater convenience for both patients and healthcare providers.

Distribution in the US is expected to begin in 2026, followed by availability in the EU in 2027. At the same time, the manufacturer plans to discontinue an older, freeze-dried immunoglobulin product by the end of 2027 due to manufacturing limitations. This shift reflects a broader move toward more efficient, scalable therapies that address evolving patient needs and supply considerations.

• FDA approves belimumab autoinjector for children with active lupus nephritis

The FDA approved a 200 mg/mL autoinjector formulation of belimumab for subcutaneous use in children aged five and older with active lupus nephritis receiving standard therapy.² Belimumab was initially approved by the FDA in 2022 in this indication. This marks the first at-home subcutaneous treatment option for paediatric lupus nephritis, aiming to reduce the burden of frequent clinic visits and support continuity of care.

Belimumab, a B-lymphocyte stimulator-specific monoclonal antibody, is the only approved biologic for both systemic lupus erythematosus and lupus nephritis. It is not recommended for patients with severe active central nervous system involvement. The approval provides a more flexible treatment option for paediatric patients, who often experience more severe disease than adults, and supports home administration as a means to improve quality of life and adherence.

• FDA and MHRA approval of sebetralstat for acute hereditary angioedema attacks

The FDA and MHRA have approved sebetralstat, the first and only oral on-demand treatment for acute hereditary angioedema (HAE) attacks in patients aged 12 and older.^3,4 Prior to this, all approved on-demand treatments required intravenous or subcutaneous administration, posing barriers to timely self-treatment. Sebetralstat is a plasma kallikrein inhibitor designed to provide rapid relief when taken at the onset of HAE symptoms.

Approval was based on results from the KONFIDENT phase III trial (NCT05259917), which demonstrated faster symptom relief, reduced attack severity, and a similar safety profile, when compared to placebo.⁵ Real-world data from the KONFIDENT-S extension trial further confirmed its rapid onset of action and consistent safety profile across over 1,700 treated attacks.

Sebetralstat empowers patients with greater independence and aligns with treatment guidelines recommending early intervention. With its dual approvals in the US and UK, sebetralstat is poised to become a foundational therapy in HAE management.

• FDA 510(k) clearance received for HyHub and HyHub Duo devices

The FDA granted 510(k) clearance for HyHub and HyHub Duo devices, designed to simplify home or clinical administration of immune globulin infusion with recombinant human hyaluronidase in patients aged 17 and older.⁶ These docking systems allow for needle-free transfer from vials and reduce the number of steps required to prepare dual vial units, which include separate vials of immunoglobulin and hyaluronidase.

• New Drug Application submitted to the FDA for investigational plaque psoriasis treatment, icotrokinra

A New Drug Application was submitted to the FDA for icotrokinra, an investigational oral peptide that selectively blocks the IL-23 receptor, for the treatment of moderate-to-severe plaque psoriasis in adults and adolescents aged 12 and older.⁷ The application included data from the ICONIC program, which included four phase III studies; ICONIC-LEAD (NCT06095115), ICONIC-TOTAL (NCT06095102), ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604). Data from the phase III trials demonstrated that once-daily icotrokinra met all primary and secondary endpoints, including significant skin clearance and a favourable safety profile.

Across studies, icotrokinra showed efficacy in difficult-to-treat areas and achieved superiority over deucravacitinib. Adverse event rates were comparable between icotrokinra (49.1%) and placebo (51.9%), with no new safety signals. Long-term data and results from a head-to-head trial comparing icotrokinra to an injectable biologic are forthcoming. If approved, icotrokinra would represent the first IL-23 receptor blocker and a potential shift in oral treatment options for plaque psoriasis.

Trial results

• Secukinumab did not meet its primary endpoints in the phase III GCAptAIN study

Top-line results from the phase III GCAptAIN study (NCT04930094) showed that secukinumab did not meet its primary endpoint of sustained remission at Week 52 in patients with newly diagnosed or relapsing giant cell arteritis (GCA).⁸ The GCAptAIN trial was a randomized, double-blind, placebo-controlled study involving three treatment arms, conducted across 27 countries. The trial compared secukinumab plus a 26-week steroid taper to placebo plus a 52-week taper. No statistically significant difference was observed in sustained remission between the groups.

The secondary endpoints did not show statistical superiority; however, secukinumab was associated with numerically lower cumulative steroid use and reduced steroid-related toxicity. The safety profile of secukinumab in GCA was consistent with existing data from its approved uses. A full analysis of the study is planned for future presentation.

• Positive topline findings from the phase III ABTECT 8-week induction trials investigating obefazimod

Positive topline results were announced from the phase III ABTECT-1 (NCT05507203) and ABTECT-2 (NCT05507216) induction trials investigating obefazimod, a first-in-class, oral miR-124 enhancer, in adults with moderately-to-severely active ulcerative colitis.⁹ Conducted across 36 countries and over 600 sites, the ABTECT trials included 1,275 participants and represent one of the largest phase III ulcerative colitis programs to date. Both 8-week trials met their primary FDA endpoint of clinical remission at the 50mg once-daily dose, with statistically significant placebo-adjusted remission rates of 19.3% (p<0.0001) in ABTECT-1 and 13.4% (p=0.0001) in ABTECT-2. All key secondary endpoints were also met.

The 25mg dose of obefazimod met the primary endpoint with statistical significance in ABTECT-1, with a placebo-adjusted remission rate of 21.4%. Significance was not achieved in ABTECT-2 for the primary endpoint; however, pooled data showed a placebo-adjusted clinical response rate of 28.6%. The safety profile was consistent with previous studies, and obefazimod was generally well tolerated. Results from the ongoing 44-week maintenance trial are expected in Q2 2026 and will inform planned regulatory submissions.

• Positive topline findings from the phase III UP-AA trial of upadacitinib

Positive topline results were reported from the phase III Up-AA trial (NCT06012240) evaluating upadacitinib in adults and adolescents with severe alopecia areata.¹⁰ At week 24 of the study, 44.6% and 54.3% of patients receiving 15mg and 30mg upadacitinib, respectively, achieved at least 80% scalp hair coverage (SALT score ≤ 20), compared to 3.4% with placebo (p<0.001).

In terms of secondary endpoints, 36.0% and 47.1% of patients receiving 15mg and 30mg upadacitinib, respectively, achieved 90% or more scalp hair coverage (SALT ≤ 10), vs 1.4% of patients receiving placebo (p<0.001). Furthermore, both doses improved eyebrow and eyelash regrowth. Complete scalp regrowth (SALT = 0) was also observed in a subset of patients with both doses of upadacitinib. The safety profile was consistent with known data, with low rates of serious adverse events and no major safety signals reported. The most common side effects included acne, nasopharyngitis, and upper respiratory tract infection.

• Endpoints not met in phase IIb trial of repibresib gel in nonsegmental vitiligo 

Topline results from a phase IIb trial evaluating repibresib gel in nonsegmental vitiligo showed the study did not meet its primary endpoint.¹¹ The randomized, double-blind trial assessed once-daily doses of 1%, 2%, and 3% repibresib gel versus vehicle in 177 participants over 24 weeks. The proportion of patients receiving 1%, 2%, and 3% repibresib, who achieved at least 50% improvement in facial Vitiligo Area Scoring Index from baseline (F-VASI50) did not differ significantly from vehicle (19.5%, 16.3% and 17.4%, respectively vs 23.4%).

The trial did not meet the key secondary endpoint of F-VASI75. Whereas, the 3% dose showed nominally significant improvements in percent change from baseline in both F-VASI and total Vitiligo Area Scoring Index (T-VASI) compared to vehicle. High vehicle response rates and elevated dropout rates in active treatment arms were noted. Based on these results, the extension phase of the trial has been discontinued.

Other updates

• The CHMP have adopted a positive opinion, recommending marketing authorisation for a ustekinumab biosimilar for the treatment of adults and children with plaque psoriasis and adults with psoriatic arthritis or Crohn’s disease.¹²