AstraZeneca Discontinues Phase III eVOLVE-Lung02 Trial of Volrustomig in Metastatic NSCLC; argenx Announces Favorable Topline Results from Phase 3 ALKIVIA Study of Efgartigimod; Bristol Myers Squibb’s ZENBEXUS Receives U.S. FDA Accelerated Approval in Combination with Daratumumab and Dexamethasone for Multiple Myeloma; Zealand Pharma Secures USD 100 Million in Royalty Financing Through Agreement with Royalty Pharma for Rusfertide; PTC Advances Rare Disease Strategy with Acquisition of ST-920 Fabry Disease Program

AstraZeneca Ends eVOLVE-Lung02 Phase III Trial Evaluating Volrustomig Plus Chemotherapy

AstraZeneca has decided to discontinue the Phase III eVOLVE-Lung02 trial, which was assessing volrustomig in combination with chemotherapy as a first-line treatment for patients with metastatic non-small cell lung cancer (mNSCLC) and tumors expressing PD-L1 at less than 50%. The study compared this combination with pembrolizumab plus chemotherapy.

The decision follows a planned review of the trial data by the Independent Data Monitoring Committee (IDMC). Based on its assessment, the committee determined that the volrustomig-based regimen was unlikely to achieve either of the study’s dual primary endpoints, progression-free survival (PFS) and overall survival (OS), in the primary analysis population comprising patients with PD-L1-negative tumors (<1%), compared with the control arm. The safety and tolerability profile of volrustomig combined with chemotherapy remained consistent with the established safety profiles of the individual treatments, with no new safety concerns reported.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said the eVOLVE-Lung02 study was initiated to address the unmet need among patients with lung cancer characterized by lower PD-L1 expression, who may experience less durable responses to existing immunotherapy approaches. Although the company is disappointed with the outcome, it intends to apply the learnings from the study to its ongoing efforts to develop innovative treatments through its oncology pipeline.

AstraZeneca will collaborate with investigators to maintain continuity of care and ensure appropriate follow-up for patients participating in the trial. Meanwhile, other Phase III studies of volrustomig in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma will proceed as planned.

argenx Announces Positive Phase 3 ALKIVIA Results for Efgartigimod in Autoimmune Myositis

argenx SE reported positive topline results from the Phase III ALKIVIA trial evaluating VYVGART® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) in adults with autoimmune myositis. The study met its primary endpoint (p=0.0011), with efgartigimod demonstrating a statistically significant and clinically meaningful 15.4-point greater improvement in mean Total Improvement Score (TIS) at Week 52 compared with placebo in the combined immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM) population (47.95 vs. 32.56). 

Treatment benefits emerged as early as Week 4 and remained statistically significant and sustained through Week 52, including during steroid tapering. Efficacy was consistent across disease subtypes, with the prespecified IMNM analysis meeting the primary endpoint (p=0.0048) and showing a 14.8-point greater improvement in mean TIS versus placebo at Week 52 (45.05 vs. 30.24). In patients with dermatomyositis, efgartigimod delivered a clinically meaningful 14.5-point improvement over placebo (51.51 vs. 36.96), although statistical significance was not reached in the smaller patient cohort (p=0.1093). 

All six core set measures contributing to the TIS favored efgartigimod across both IMNM and DM, reflecting improvements in muscle strength, physical functioning, and disease activity beyond muscle involvement, while patients with DM also experienced improvements in skin disease activity. Efgartigimod was generally well tolerated, with a safety profile consistent with previous studies and its established safety profile.

Bristol Myers Squibb’s First CELMoD Therapy ZENBEXUS™ Wins FDA Accelerated Approval for Multiple Myeloma

Bristol Myers Squibb announced that the FDA has approved ZENBEXUS™ (iberdomide) in combination with daratumumab and hyaluronidase-fihj plus dexamethasone (ZDd) for adults with multiple myeloma who have received at least one prior line of therapy that included both a proteasome inhibitor and an immunomodulatory agent. Full approval of the indication is subject to confirmation and characterization of clinical benefit in one or more confirmatory trials. ZENBEXUS represents the first FDA-approved cereblon E3 ligase modulator (CELMoD), a novel class of cereblon-modulating protein degraders developed for multiple myeloma. The product carries Boxed WARNINGS for embryo-fetal toxicity and venous and arterial thromboembolism and is contraindicated in pregnant women.

The approval was supported by findings from the Phase III EXCALIBER-RRMM trial, which compared ZDd (n=207) with daratumumab, bortezomib, and dexamethasone (DVd; n=213) in patients with relapsed or refractory multiple myeloma (RRMM). At a median follow-up of 16 months, ZDd achieved a statistically significant improvement in one of the trial’s dual primary endpoints, with 41% of patients (n=85; 95% CI: 34–48) achieving minimal residual disease (MRD)-negative complete response (CR), compared with 21% (n=44; 95% CI: 15–27) in the DVd arm (p<0.0001). MRD negativity is considered one of the deepest measures of treatment response in multiple myeloma and is associated with improved progression-free survival (PFS). The decision marks the first FDA approval for RRMM supported by MRD-negative CR as the basis of the regulatory decision.

ZENBEXUS previously received Breakthrough Therapy designation and accelerated approval based on achievement of MRD-negative CR at any point during the EXCALIBER-RRMM study. The application was reviewed through the FDA’s Project Orbis initiative, which facilitates coordinated regulatory reviews among participating international health authorities.

Although ZENBEXUS is the first CELMoD therapy to receive FDA approval, mezigdomide, another investigational CELMoD, is also being evaluated by the agency. Its New Drug Application for use in combination with carfilzomib and dexamethasone is currently under FDA review, with a Prescription Drug User Fee Act (PDUFA) target action date of May 13, 2027.

Zealand Pharma Signs USD 100 Million Royalty Sale Agreement with Royalty Pharma Related to Rusfertide

Zealand Pharma A/S has entered into a royalty purchase and sale agreement with Royalty Pharma plc, under which Royalty Pharma will acquire Zealand Pharma’s economic interests in rusfertide (PTG-300), a potential first-in-class treatment for polycythemia vera, a rare and chronic blood disorder.

Under the agreement, Zealand Pharma will receive a total of USD 100 million in consideration for its economic interests in rusfertide, which include a 1% royalty on potential future worldwide net sales as well as certain regulatory and commercial milestones. The transaction includes an upfront payment of USD 50 million upon closing, with the remaining USD 50 million payable on the first anniversary of the transaction’s completion.

Zealand Pharma will continue to be entitled to a 0.25% royalty on annual global net sales of rusfertide exceeding USD 1.5 billion, while Royalty Pharma will receive a 0.75% royalty on sales above this threshold.

Henriette Wennicke, Chief Financial Officer at Zealand Pharma, said the company was pleased to partner with Royalty Pharma in the strategic financing transaction. She noted that the agreement enables Zealand Pharma to convert a potential future royalty stream into near-term capital, which will be allocated toward future growth opportunities in accordance with the company’s strategic priorities under its Metabolic Frontier 2030 strategy.

The U.S. FDA has established a Prescription Drug User Fee Act (PDUFA) target action date in the third quarter of 2026 for the NDA seeking approval of rusfertide for adults with polycythemia vera. Takeda is responsible for the therapy’s global commercialization.

PTC Bolsters Rare Disease Portfolio with Acquisition of Fabry Disease Therapy ST-920

PTC Therapeutics, Inc. announced that it had been named the winning bidder for ST-920, a BLA-stage, one-time AAV gene therapy for Fabry disease, following a competitive bankruptcy auction conducted by Sangamo Therapeutics. Under the agreement, PTC will pay $111 million upfront, with the potential for an additional $100 million in contingent milestone payments tied to specified regulatory approvals. A rolling Biologics License Application (BLA) submission to the U.S. FDA seeking accelerated approval of ST-920 is expected to be completed in the fourth quarter of 2026. The application is supported by clinical data from the Phase 1/2 STAAR study demonstrating a meaningful beneficial effect on renal function, along with a favorable safety and tolerability profile through 52 weeks.

ST-920 is a single-dose AAV gene therapy intended to provide sustained production of the deficient α-Gal A enzyme, resulting in substantial reductions in globotriaosylceramide (Gb3) levels. Clinical findings have shown durable benefits while potentially reducing the treatment burden associated with lifelong enzyme replacement therapy (ERT). The therapy has received several FDA designations, including Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug, and Fast Track designations.

Data from the Phase 1/2 STAAR trial showed a positive mean annualized estimated glomerular filtration rate (eGFR) slope at Week 52 following treatment with ST-920, together with favorable effects on other manifestations of Fabry disease, including cardiac function and quality of life. The improvement in eGFR over 52 weeks represents a notable distinction from certain existing Fabry therapies, which have demonstrated renal benefits but continued to show a negative eGFR slope from baseline. Importantly, all participants who were receiving ERT at the beginning of the study were subsequently discontinued from ERT.

ST-920 has also demonstrated sustained biological activity, with elevated α-Gal A activity maintained for as long as 4.5 years in the earliest treated participant, alongside evidence of continued renal function improvements across the study population. The therapy has additionally shown an encouraging safety and tolerability profile, without the need for routine prophylactic or post-infusion systemic immunosuppression.

The accelerated-approval BLA is being supported by the intermediate clinical endpoint of annualized eGFR at Week 52, in alignment with discussions with the FDA. Results from the STAAR study at 104 weeks are planned to serve as confirmatory evidence for a potential traditional approval. PTC has already submitted the nonclinical and clinical components of the BLA through a rolling submission, while the chemistry, manufacturing, and controls (CMC) module is expected to be filed in Q4 2026. Beyond the United States, PTC intends to seek regulatory approvals in international markets by leveraging its established rare-disease regulatory and commercial infrastructure.