Efzimfotase Alfa Achieves 17.05-Metre Numerical Improvement Over Placebo in Six-Minute Walk Test; Asahi Kasei Therapeutics Announces First Patient Dosed in Phase 2a Study of AIC468 for BK Virus; Teva’s WELTRUZA Gains FDA Approval for Once-Monthly Treatment of Adult Schizophrenia; Innovent’s SYCUME Meets Primary Endpoint in Phase 3 Inactive Thyroid Eye Disease Trial; Zealand Pharma’s Petrelintide Delivers Positive Topline Results in Phase 2 ZUPREME-2 Trial

Efzimfotase Alfa Shows Numerical Improvement in Six-Minute Walk Distance Versus Placebo in HICKORY Phase III Trial

Results from the HICKORY Phase III trial indicated that efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy, did not achieve statistical significance for the primary endpoint but showed a numerical improvement in the Six-Minute Walk Test (6MWT) among adolescents and adults aged ≥12 years with hypophosphatasia (HPP) who had not previously received Strensiq (asfotase alfa). At week 25, the treatment group demonstrated improvement in 6MWT compared with placebo.

In the overall study population, efzimfotase alfa achieved a least squares (LS) mean difference of 17.05 metres in the change from baseline in 6MWT at week 25 versus placebo (p=0.1675). The primary endpoint did not reach statistical significance, primarily due to better-than-anticipated outcomes in the placebo group of patients with adult-onset HPP.

A post hoc analysis revealed that 45.2% of patients receiving efzimfotase alfa achieved the minimum clinically important difference (MCID) in 6MWT from baseline at week 25, defined as 43 metres for adolescents and 31.1 metres for adults, compared with 30.0% of patients receiving placebo. The odds ratio was 2.50 (95% CI: 1.06–5.91; nominal p=0.0363), indicating that patients treated with efzimfotase alfa had 2.5 times the odds of achieving a clinically meaningful improvement in walking capacity.

At week 25, efzimfotase alfa also demonstrated a nominally significant improvement in the key secondary endpoint of Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), with an LS mean difference of 5.74 versus placebo (nominal p=0.0016). Other key secondary endpoints, including the 30-second Sit-to-Stand test (30s-STS), Lower Extremity Functional Scale (LEFS) and Brief Pain Inventory–Short Form (BPI-SF) Pain Severity score, also numerically favoured efzimfotase alfa.

Findings from the open-label extension showed that improvements were sustained or continued through week 49 among patients receiving efzimfotase alfa across the primary and key secondary endpoints, including 6MWT, 30s-STS, LEFS, BPI-SF Pain Severity and FACIT-Fatigue. Patients who switched from placebo to efzimfotase alfa after completing the randomised treatment period at week 25 also experienced similar improvements in mobility, physical function, pain and fatigue.

In a combined analysis of prespecified subgroups comprising adolescents and adults with paediatric-onset HPP, efzimfotase alfa demonstrated nominally significant and clinically meaningful improvements in the primary endpoint of 6MWT at week 25, with an LS mean difference of 35.6 metres versus placebo (nominal p=0.0386). Improvements were also observed in the key secondary endpoints of 30s-STS, with an LS mean difference of 1.3 (nominal p=0.0384), and BPI-SF Pain Severity, with an LS mean difference of −1.0 (nominal p=0.0260).

Among the prespecified subgroup of adults with adult-onset HPP, efzimfotase alfa showed a clinically meaningful improvement in LEFS, with an LS mean difference of 3.5 versus placebo (nominal p=0.2376), although the result was not statistically significant. The treatment also demonstrated a nominally significant and clinically meaningful improvement in FACIT-Fatigue, with an LS mean difference of 7.41 versus placebo (nominal p=0.0021).

AIC468 Enters Phase 2a Clinical Evaluation for BK Virus Infection

Asahi Kasei Therapeutics, Inc., the global specialty pharmaceutical business of Tokyo-based Asahi Kasei, announced that the first patient has been dosed in a randomized Phase 2a clinical trial (NCT07503561) investigating AIC468, a novel antiviral antisense oligonucleotide (ASO), in adults with BK virus (BKV) infection following kidney transplantation. The investigational program was developed by Aicuris Anti-infective Cures AG (Aicuris), which is now part of Asahi Kasei Therapeutics.

“Although BK virus reactivation is generally harmless in immunocompetent individuals, it remains a significant complication for kidney transplant recipients, potentially causing graft dysfunction and BK virus-associated nephropathy,” said Carl Kraus, MD, Chief Medical Officer of Asahi Kasei Therapeutics. “For transplant recipients and their families, this complication carries a substantial risk of losing the transplanted kidney. Building on encouraging Phase 1 results in healthy volunteers, dosing the first patient in this study marks a significant milestone in the development of a targeted antiviral therapy for a patient population with no approved treatment options. Our goal is to help preserve transplanted organs and improve long-term patient outcomes.”

The randomized, double-blind, placebo-controlled Phase 2a trial forms part of a broader Phase 2/3 development program evaluating AIC468 at multiple dose levels in adult kidney transplant recipients with BKV infection. The study is designed to assess the candidate’s safety, tolerability, and pharmacokinetic profile, with safety evaluations including the frequency and severity of treatment-emergent adverse events (TEAEs). Advancement into Phase 2a was supported by favorable Phase 1 findings demonstrating an encouraging safety, tolerability, and pharmacokinetic profile.

Teva Expands Schizophrenia Treatment Options with FDA Approval of WELTRUZA

Teva Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved WELTRUZA (olanzapine) extended-release injectable suspension, a novel once-monthly, subcutaneous long-acting injectable (LAI) treatment for adults with schizophrenia. Clinical trial findings showed that WELTRUZA improved symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), significantly reduced illness severity according to the Clinical Global Impression–Severity (CGI-S) scale, and enhanced personal and social functioning, as assessed by the Personal and Social Performance (PSP) scale. WELTRUZA is expected to become available in the coming weeks in three dosage strengths, 318 mg, 425 mg, and 531 mg, without requiring loading doses, oral supplementation, or post-injection monitoring.

“WELTRUZA delivers the established efficacy of olanzapine through an innovative long-acting subcutaneous injectable formulation, helping address a significant and longstanding gap in schizophrenia treatment,” said Chris Fox, Executive Vice President, U.S. Commercial and Head of Innovative Franchise at Teva. He added that WELTRUZA was designed with patients’ needs at the forefront of its development, demonstrating the potential of patient-focused innovation to deliver meaningful advances in treatment. He also noted that the approval represents an important milestone in advancing Teva’s Pivot to Growth strategy.

Olanzapine is the most widely prescribed atypical antipsychotic for schizophrenia in its daily oral formulation. However, maintaining long-term symptom control with daily medications can be challenging because of adherence difficulties, which may increase the likelihood of clinical instability and relapse. WELTRUZA was developed to address this unmet need by providing the proven therapeutic benefits of olanzapine in a convenient once-monthly subcutaneous injectable formulation.

“This approval highlights Teva’s commitment to patient-centered innovation and the capabilities of our R&D organization,” said Eric Hughes, MD, PhD, Executive Vice President, Global R&D and Chief Medical Officer at Teva. He explained that WELTRUZA combines established scientific evidence with innovative formulation technology, removing the requirement for post-injection monitoring and helping overcome a major barrier to treatment while improving care for individuals living with schizophrenia.

WELTRUZA will be offered as a once-monthly subcutaneous injection in three strengths: 318 mg, 425 mg, and 531 mg. These doses correspond to approved daily oral olanzapine doses of 10 mg, 15 mg, and 20 mg, respectively.

Innovent Reports Phase 3 Success for SYCUME in Inactive Thyroid Eye Disease

Innovent Biologics, Inc. announced that SYCUME® (Teprotumumab N01 Injection; R&D code: IBI311), its internally developed recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, has met the primary endpoint at Week 24 in RESTORE-3, a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial involving Chinese patients with inactive thyroid eye disease (TED). The study demonstrated that SYCUME® effectively reduced proptosis in patients with inactive TED while maintaining a favorable safety profile.

SYCUME® is the first IGF-1R antibody drug approved in China and the second to receive approval worldwide, addressing a treatment gap of approximately 70 years in China’s domestic TED treatment landscape. The drug was officially added to China’s National Reimbursement Drug List on January 1, 2026, helping reduce the financial burden on patients compared with the high cost of overseas alternatives and improving treatment accessibility. Approximately two-thirds of the overall TED population has inactive disease. Therefore, the positive Phase 3 results in patients with inactive TED represent another significant milestone for SYCUME® in advancing comprehensive disease management and precision treatment across the full course of TED. These findings also provide new clinical evidence supporting the treatment of inactive TED in China.

RESTORE-3 was designed to assess the efficacy and safety of IBI311 in Chinese patients with inactive TED. The trial randomized 116 eligible participants in an approximately 2:1 ratio to receive either IBI311 or placebo. The primary efficacy endpoint was the proptosis response rate in the study eye at Week 24, while the key secondary endpoint measured the change from baseline in proptosis distance in the study eye at the same time point.

The study included 116 patients with inactive TED, defined by a Clinical Activity Score (CAS) of ≤2 in both eyes. The mean disease duration was 4.3 years, and the mean baseline proptosis distance in the study eye was 22.16 mm. Approximately 74.1% of participants had a baseline CAS of 0 or 1. Against this clinical background, IBI311 demonstrated clinically meaningful efficacy and achieved both the primary and key secondary endpoints.

• Primary endpoint achieved: At Week 24, the proptosis response rate in the study eye was significantly higher among patients receiving IBI311 than among those receiving placebo, at 60.4% versus 23.5%, respectively. The treatment difference was 36.9 percentage points (p = 0.0003).
• Key secondary endpoint achieved: At Week 24, the least squares mean (LS Mean) change from baseline in proptosis distance in the study eye was −1.88 mm in the IBI311 group, compared with −0.88 mm in the placebo group. The between-group treatment difference was −1.00 mm, demonstrating statistically significant superiority for IBI311 (p < 0.0001).
• Additional benefits across both eyes: At Week 24, the proptosis response rate in the non-study eye was also higher with IBI311 than with placebo, reaching 46.0% versus 19.8%, respectively (p = 0.0071). The LS Mean change from baseline in proptosis distance in the non-study eye was −1.77 mm in the IBI311 group, compared with −0.91 mm in the placebo group (p < 0.0001). These findings were consistent with the efficacy trend observed in the study eye.
• Favorable safety and tolerability: Throughout the double-blind treatment and follow-up periods, IBI311 demonstrated a favorable safety and tolerability profile. Most treatment-emergent adverse events were mild to moderate in severity, and no new safety signals were identified.

Follow-up in RESTORE-3 remains ongoing, with the complete study findings expected to be presented at future academic conferences or published in peer-reviewed journals. Although the mean baseline proptosis distance in RESTORE-3 was lower than that reported in the TEPEZZA® study, an indirect comparison indicated that IBI311’s proptosis response rate and degree of proptosis reduction were generally consistent with the results reported for TEPEZZA® in patients with inactive TED.

Zealand Pharma Announces Encouraging Topline Results from Phase 2 ZUPREME-2 Trial of Petrelintide

Zealand Pharma A/S announced positive topline results from the Phase 2 ZUPREME-2 trial, which assessed the efficacy and safety of petrelintide compared with placebo in 220 adults living with overweight or obesity and type 2 diabetes. Participants had a mean baseline body mass index (BMI) of 36.3 kg/m² and a mean baseline glycated hemoglobin (HbA1c) level of 8.0%.

The study achieved its primary endpoint, showing that once-weekly subcutaneous administration of petrelintide, with dose escalation every four weeks, produced statistically significant and clinically meaningful weight reductions from baseline at Week 28 across all three treatment arms compared with placebo. Under the efficacy estimand, participants receiving petrelintide experienced mean body weight reductions of up to 9.2%, ranging from 7.4% to 9.2% across the treatment groups, compared with 2.0% in the placebo group. The results were largely consistent under the treatment regimen estimand. Petrelintide also demonstrated clinically meaningful improvements in glycemic control across all three treatment arms, with placebo-adjusted HbA1c reductions ranging from 0.61% to 0.88%.

According to David Kendall, MD, Chief Medical Officer at Zealand Pharma, the findings further strengthen petrelintide’s potential as a treatment for chronic weight management and, for the first time, demonstrate its promise as a standalone therapy for individuals with overweight or obesity and type 2 diabetes. He highlighted the clinically meaningful weight loss achieved alongside a favorable tolerability profile and improvements in glycemic control, noting that both outcomes are important for delivering sustained, long-term benefits in this patient population. Zealand Pharma and its partner Roche plan to further evaluate petrelintide through their recently initiated Phase 3 registrational program to address significant unmet needs in chronic weight management.

Petrelintide’s safety profile revealed no unexpected safety signals, and its tolerability was generally favorable and comparable to placebo. Discontinuations due to gastrointestinal adverse events (AEs) occurred in 1.9% of participants receiving petrelintide, compared with 1.7% of those receiving placebo. Gastrointestinal events were the most commonly reported AEs, with the vast majority being mild and occurring during the dose-escalation period.

The safety and tolerability findings from ZUPREME-2 are consistent with those observed in the 42-week Phase 2 ZUPREME-1 trial, which evaluated petrelintide in individuals with overweight or obesity without type 2 diabetes. Full results from ZUPREME-2 are expected to be presented at an upcoming scientific conference.

Zealand Pharma and Roche have initiated a Phase 3a clinical development program for petrelintide comprising three trials: ZUPREME-3, ZUPREME-4, and ZUPREME-5. These studies will evaluate the efficacy and safety of once-weekly petrelintide compared with placebo in three distinct populations: individuals with obesity or overweight without type 2 diabetes, individuals with obesity or overweight and type 2 diabetes, and individuals with obesity or overweight and established cardiovascular disease, respectively. Collectively, the trials are expected to enroll approximately 7,000 participants, with the first participants having already begun treatment.