Ultomiris Phase III Trial Update Highlights Progress in Post-Transplant TMA; argenx Acquires Forte Biosciences; Otsuka’s SIMTRIYO Receives FDA Nod as a First-in-Class ADHD Treatment; Outlook Therapeutics Secures FDA Approval for LYTENAVA to Treat Wet AMD; Merck Reveals Future Access Strategy for Once-Monthly Oral HIV Prevention Therapy Alimatravir

Phase III Ultomiris Trial Reports Progress in Adults and Adolescents with HSCT-Related TMA

Topline findings from the Phase III ALXN1210-TMA-313 trial indicated that Ultomiris (ravulizumab) did not meet the primary endpoint of event-free survival over 26 weeks versus placebo in adults and adolescents (12 years and older) with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). The primary endpoint measured the time from randomization to either TMA-related clinical deterioration or death, whichever occurred first.

In contrast, the open-label Phase III ALXN1210-TMA-314 study in pediatric patients demonstrated encouraging survival outcomes, with overall survival rates of 87.2% at 26 weeks and 73.4% at 52 weeks, consistent with previously reported data. Supported by these findings and evidence from the external control study ALX-TMA-502, Alexion and AstraZeneca Rare Disease are advancing regulatory submissions for Ultomiris in pediatric HSCT-TMA, citing meaningful improvements in overall survival.

Although the adult and adolescent study failed to achieve statistical significance for its primary endpoint, Ultomiris showed a favorable trend toward clinical benefit at 26 weeks compared with placebo. Alexion continues discussions with regulatory authorities to evaluate these findings alongside emerging real-world evidence.

HSCT-TMA is a rare but severe complication that can develop following hematopoietic stem cell transplantation, a procedure increasingly used to treat various cancers and other serious diseases. The condition is characterized by damage to small blood vessels and the formation of blood clots, which can lead to multiple organ failure and death. In the United States, fewer than 6,000 individuals are estimated to develop HSCT-TMA.

Commenting on the pediatric findings, Christopher Dvorak, MD, Professor and Chief of the Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation at UCSF Benioff Children’s Hospitals, emphasized that children with HSCT-TMA face a poor prognosis without targeted therapies. He noted that the survival outcomes observed in the Phase III pediatric study represent a clinically meaningful advancement and may pave the way for a much-needed treatment option for this life-threatening post-transplant complication.

Vincent Ho, MD, Director of Clinical Operations for Adult Hematopoietic Stem Cell Transplantation at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, highlighted the complexity of conducting randomized global trials in HSCT-TMA. While acknowledging that the adult and adolescent study did not reach its primary endpoint, he stated that the results contribute valuable insights that, together with real-world evidence, could improve understanding and management of this challenging condition.

Marc Dunoyer, Chief Executive Officer of Alexion, described the program as the largest global registrational effort in HSCT-TMA and the only placebo-controlled study conducted in adults with the disease. He reaffirmed the company’s commitment to pursuing regulatory approval for pediatric HSCT-TMA based on the positive survival data while continuing to engage with global health authorities regarding potential pathways for the adult indication and further analyses incorporating real-world evidence.

Across both the ALXN1210-TMA-313 and ALXN1210-TMA-314 studies, Ultomiris demonstrated a safety profile consistent with its established clinical experience and with the safety outcomes typically observed in patients undergoing hematopoietic stem cell transplantation.

argenx Completes Forte Biosciences Acquisition, Expanding Immunology Pipeline

argenx has entered into a definitive agreement to acquire Forte Biosciences in an all-cash transaction valued at approximately $2.2 billion, with shareholders set to receive $77 per share. The acquisition strengthens argenx’s immunology pipeline by adding FB102, a first-in-class anti-CD122 antibody that has demonstrated encouraging clinical proof-of-concept in vitiligo and celiac disease, with broader potential across multiple autoimmune disorders. The deal aligns with argenx’s long-term strategy of expanding its portfolio through innovative therapies that address significant unmet medical needs and have the potential to transform treatment standards.

Karen Massey, Chief Executive Officer of argenx, stated that the acquisition reinforces the company’s Vision 2030 strategy and its commitment to becoming a leading innovator in immunology. She highlighted that FB102 fits well within argenx’s development approach due to its compelling biological rationale, promising clinical validation, and broad therapeutic potential. Massey also acknowledged Forte Biosciences’ contributions and expressed confidence in advancing the program to benefit patients worldwide.

Paul A. Wagner, Ph.D., Chief Executive Officer and Chairperson of Forte Biosciences, noted that the agreement positions FB102 for accelerated global development under argenx’s leadership. He emphasized that combining the antibody’s favorable clinical profile with argenx’s development expertise and commercial capabilities could expand treatment opportunities for patients with vitiligo, celiac disease, alopecia areata, and other autoimmune conditions.

The acquisition follows encouraging clinical progress for FB102. Forte Biosciences recently reported positive Phase 1b results in vitiligo, demonstrating statistically significant treatment benefits, while earlier Phase 1b findings in celiac disease also showed promising outcomes. With Phase 2 celiac disease data anticipated later this year, these positive clinical results were key factors influencing argenx’s decision to transition from a strategic investment to a full acquisition. In addition to its lead indications, FB102 is being explored for its potential in alopecia areata and several other autoimmune diseases, positioning it as a potential multi-indication asset.

FB102 further expands argenx’s antibody-based immunology portfolio, complementing programs such as efgartigimod, empasiprubart, adimanebart, and ARGX-121. By targeting pathogenic T-cell and natural killer (NK)-cell activity, the therapy introduces a differentiated mechanism of action that enhances argenx’s ability to develop treatments for a broader range of immune-mediated diseases.

Otsuka Wins FDA Approval for Innovative SIMTRIYO to Treat ADHD

Otsuka Pharmaceutical Co., Ltd. has received U.S. FDA approval for SIMTRIYO® (centanafadine), a once-daily extended-release capsule indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and children aged 6 years and older weighing at least 20 kg. Approved on July 24, SIMTRIYO is the first and only norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) authorized for ADHD, offering a novel therapeutic option for patients and healthcare providers. By preventing the reuptake of these three neurotransmitters, the therapy enhances their availability in neural pathways associated with attention and behavioral control. As a central nervous system (CNS) stimulant, SIMTRIYO is anticipated to become commercially available later this year following scheduling by the U.S. Drug Enforcement Administration (DEA).

The FDA approval was based on data from four pivotal Phase III clinical trials assessing the efficacy and safety of SIMTRIYO in pediatric, adolescent, and adult patients with ADHD. Across these studies, the treatment achieved statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo. Efficacy was evaluated using the ADHD Rating Scale-5 (ADHD-RS-5) in children and adolescents and the Adult ADHD Investigator Symptom Rating Scale (AISRS) in adults. Symptom improvements were observed as early as the first week of treatment in both pediatric and adult populations. The most frequently reported adverse events included decreased appetite, nausea, rash, headache, and abdominal pain in children and adolescents, while adults commonly experienced headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea.

Commenting on the approval, John Kraus, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Otsuka Pharmaceutical Development & Commercialization (OPDC), stated that SIMTRIYO represents a significant advancement for individuals living with ADHD by introducing an innovative mechanism of action. He emphasized that ADHD is a complex condition affecting patients from childhood through adulthood and noted that the approval reflects the company’s commitment to developing therapies that address the diverse needs of patients and their families. He also acknowledged the contributions of patients, caregivers, investigators, and clinical research teams who participated in the development program.

Otsuka continues to strengthen the clinical evidence supporting centanafadine through ongoing research. A recently completed Phase IIIb trial involving adults with ADHD and coexisting anxiety demonstrated statistically significant improvements in ADHD symptoms compared with placebo, further expanding understanding of the drug’s clinical potential. Detailed findings from this study are expected to be presented at an upcoming scientific conference.

Outlook Therapeutics’ LYTENAVA Becomes the First FDA-Approved Ophthalmic Bevacizumab for Wet AMD

Outlook Therapeutics, Inc. has received U.S. FDA approval for LYTENAVA™ (bevacizumab-vikg) for the treatment of neovascular age-related macular degeneration (nAMD), also known as wet AMD. This milestone makes LYTENAVA™ the first and only FDA-approved ophthalmic formulation of bevacizumab specifically indicated for wet AMD in the United States.

Unlike compounded alternatives, LYTENAVA is specifically developed for ophthalmic use and is supported by robust clinical data, validated manufacturing processes, FDA-approved labeling, comprehensive quality standards, and continuous regulatory oversight. The company also expects the therapy to receive 12 years of Reference Product Exclusivity under the Biologics Price Competition and Innovation Act (BPCIA).

With this approval, Outlook Therapeutics aims to establish a new benchmark for ophthalmic bevacizumab therapy, positioning LYTENAVA as the FDA-approved standard of care for patients with wet AMD. Bevacizumab is already widely used as a first-line anti-VEGF treatment for the condition, highlighting its critical role in retinal disease management. Given that wet AMD is a progressive retinal disorder and a leading cause of vision loss in older adults, long-term treatment consistency, product quality, and manufacturing reliability remain essential for patient care.

LYTENAVA is entering the U.S. anti-VEGF retinal therapeutics market, which is valued at approximately USD 8.5 billion annually and supports millions of intravitreal injections each year. Outlook Therapeutics is now advancing the product’s commercial rollout by expanding reimbursement and patient support programs, strengthening its specialized retina-focused commercial team, assisting healthcare providers nationwide, and positioning LYTENAVA as the trusted FDA-approved ophthalmic bevacizumab across the U.S.

Merck Unveils Initial Access Strategy for Investigational Once-Monthly HIV PrEP Candidate Alimatravir

Merck has unveiled the initial elements of a comprehensive strategy designed to accelerate broad and sustainable access to alimatravir (MK-8527), its investigational once-monthly oral HIV-1 pre-exposure prophylaxis (PrEP), across low- and middle-income countries (LMICs), pending regulatory approval. The strategy includes plans to establish early voluntary generic licensing covering 129 LMICs, strengthen regional manufacturing capacity in Africa and Latin America, and invest in advanced manufacturing to ensure timely product availability in areas with significant unmet need. These initiatives were announced ahead of the 26th International AIDS Conference in Rio de Janeiro, Brazil.

Key Highlights:

• Early access planning for LMICs: Merck is implementing its access strategy during the ongoing Phase III clinical program, even before trial enrollment is complete, with the objective of enabling rapid, widespread, and equitable access to alimatravir in LMICs if it receives regulatory approval.
• Community-informed approach: The company’s access framework has been developed through extensive collaboration with HIV advocacy groups, community organizations, and global health stakeholders, with continued engagement planned throughout the Phase III development process.
• A promising new PrEP alternative: If approved, alimatravir could become a convenient once-monthly oral PrEP option, offering up to one month of HIV-1 protection with a single pill and an anticipated onset of protection within one hour after administration.

Despite the availability of multiple HIV prevention strategies, including daily oral PrEP, long-acting injectable PrEP, and other evidence-based interventions, HIV remains a major global health challenge. Approximately 1.2 million people acquired HIV in 2025, averaging nearly 3,300 new infections each day. According to the 2024 UNAIDS report, only 3.5 million individuals were using oral PrEP in 2023, underscoring the need to significantly expand access to achieve the global target of 20 million people receiving PrEP by 2030. Merck’s proposed access initiatives aim to support large-scale PrEP adoption while addressing longstanding barriers such as affordability, limited availability, and stigma associated with HIV prevention.