Zachary Zubulake

FDA granted priority review for the supplemental Biologics License Application (sBLA) for marstacimab, marketed as HYMPAVZI.¹ This medicine is intended for the 

treatment of patients with hemophilia A or B

, and the application seeks to expand the current indication to include patients aged 6 and older with inhibitors, as well as pediatric patients aged 6 to 11 without inhibitors. This review comes as the landscape of hemophilia treatment is shifting toward non-factor prophylactic options that simplify administration and address biological resistance.

Marstacimab is notable as the first anti-tissue factor pathway inhibitor (TFPI) approved in the United States and the 

. Unlike traditional factor replacement therapies that replace missing factor VIII or factor IX, marstacimab targets the Kunitz 2 domain of TFPI.¹ This mechanism is intended to re-establish the balance between bleeding and clot formation. The product's use of a pre-filled, once-weekly subcutaneous auto-injector pen is a critical design element, as it eliminates the need for the routine treatment-related lab monitoring and complex preparation often associated with intravenous infusions.

How Do Recent Clinical Trial Outcomes Address the Challenges of Pediatric Patients?

The clinical evidence supporting these expanded indications stems from the BASIS and BASIS KIDS Phase 3 trials. These studies address populations with a high degree of unmet medical need, particularly those who have developed inhibitors, referring to antibodies that neutralize factor replacement therapies and render them ineffective. Michael Vincent, MD, PhD, chief inflammation & immunology officer at Pfizer, emphasized the importance of these developments in a press release:¹ “There is a significant medical need for younger patients with hemophilia and for those who have developed inhibitors, which neutralize factor replacement therapies and render them ineffective.” He further noted, “Based on the findings in the BASIS clinical trial program and if approved, we believe HYMPAVZI has the potential to become a transformative option for these patients that have limited or burdensome treatment options today. We look forward to progressing discussions with regulators to make this medicine available for patients.”

Repeated bleeding episodes in children can lead to permanent joint damage due to the vulnerability of growing cartilage and bone. Guy Young, MD, director of the Hemostasis and Thrombosis Center at Children's Hospital, Los Angeles, explained the necessity of preventative care for this demographic,¹ “for children living with hemophilia A or B between ages 6 and 11, treatment approaches that prevent bleeds are particularly important to protect growing joints.” He added that “HYMPAVZI would address a critical unmet medical need for these patients and those with inhibitors if approved, particularly patients ages 6 to 11 with hemophilia B who do not have non-factor treatment options available today.”¹

The BASIS trial evaluated the efficacy and safety of marstacimab by measuring the treated annualized bleeding rate over a 12-month active treatment period. In the BASIS KIDS study, 68 patients aged 6-11 were treated with a regimen consisting of a 150 mg loading dose followed by 75 mg once weekly.¹ These trials are essential to understanding the safety profile of anti-TFPI therapies, which may include risks such as thromboembolic events or allergic reactions. Beyond the United States, the use of marstacimab for patients 12 years and older with inhibitors is also under review by the EMA. This global regulatory activity underscores the industry's drive to provide stable, subcutaneous alternatives for more than 800,000 people living with hemophilia worldwide.

How Are Other Pfizer Biologics Progressing?

Beyond advancements in hematology, the pharmaceutical industry is witnessing a parallel evolution in long-acting metabolic therapies. Topline results from the Phase 2b VESPER-3 

 receptor agonist PF-08653944 demonstrated that switching from weekly titration to monthly maintenance dosing achieved significant weight loss, reaching 12.3% at 28 weeks.²

Why Does the Transition to Monthly Maintenance Dosing Matter for Metabolic Therapy?

A four-fold reduction in dosing frequency addresses significant barriers to patient adherence and simplifies supply logistics. Jim List, MD, PhD, stated in a press release,² “These topline results from the Phase 2b VESPER-3 study reinforce the potential of PF’3944 as a monthly treatment with competitive efficacy.” Dr. List noted that PF-08653944 serves as a key anchor in addressing critical care gaps.

How Does the Expansion of Long-Acting Injectable Pipelines Influence Development Strategies?

Advancing 10 Phase 3 trials in 2026 highlights a strategic push to address the global obesity epidemic and its associated comorbidities.² This shift toward monthly subcutaneous options within 

 agonist class reflects a developmental priority to provide less burdensome treatment alternatives for chronic metabolic conditions.

FDA Grants Priority Review for HYMPAVZI® (marstacimab) sBLA for the Treatment of Two Hemophilia A or B Patient Populations with Significant Medical Need

Pfizer’s Ultra-Long-Acting Injectable GLP-1 RA Shows Robust and Continued Weight Loss with Monthly Dosing in Phase 2b Trial. Press Release

Articles

FDA priority review is underway for marstacimab (HYMPAVZI) sBLA to extend use to patients ≥6 years with inhibitors and children 6–11 without inhibitors, reflecting momentum toward non-factor prophylaxis. As the first approved anti-TFPI therapy in the US/EU, marstacimab targets TFPI’s Kunitz 2 domain and is delivered via once-weekly subcutaneous auto-injector, reducing infusion burden and monitoring. Phase 3 BASIS/BASIS KIDS data support pediatric relevance amid inhibitor-driven resistance and joint-protective prophylaxis needs. Pfizer also reported Phase 2b monthly GLP-1 RA maintenance dosing with 12.3% weight loss.

FDA granted priority review for Pfizer’s Marstacimab, a weekly subcutaneous anti-TFPI to treat pediatric and inhibitor hemophilia.

FDA Grants Priority Review For Pfizer’s Marstacimab for Hemophilia A or B

Marcio Temtem, vice president, Strategic Business Management, Hovione, addresses molecule complexity, speed, and regionalization via integrated manufacturing.

Hovione’s Strategy for Complexity, Speed, and Regional Supply Chains

The landscape of small molecule manufacturing is rapidly evolving, according to Marcio Temtem, vice president, Strategic Business Development, Hovione, who provides an expert look into how his firm is evolving their approach as the industry changes. With 17 years of experience at Hovione, a family-owned CDMO with a 66-year legacy, Temtem identifies three pivotal trends currently shaping the industry: increased complexity, accelerated development speed, and the regionalization of supply chains.

Temtem observes that small molecules have grown significantly in size and complexity, often requiring multiple chemical steps and high-potency handling. This shift necessitates a specialized "toolbox" to overcome modern bioavailability challenges. Highlighting Hovione's technical approach to these hurdles, Temtem states, "We use a platform called amorphous solid dispersions, produced by spray drying to address this challenge of bioavailability.” This platform represents a core area in which Hovione maintains global leadership, utilizing innovative tools to scale processes efficiently while minimizing the use of APIs.

Temtem also mentions the increased influence of AI in drug discovery and deployment, which requires CDMOs to bridge the gap from grams to tons at a much faster pace than in previous years. He further addresses the trend of regionalization, noting the rise of countries such as the US and China prioritizing regional supply chain strategies. He explains that Hovione is uniquely positioned to navigate these new challenges with supply chains through its FDA-inspected sites across three continents.

Central to Hovione’s competitive advantage is their integrated manufacturing offer, which combines drug substance and drug product expertise at a single location. Temtem emphasizes the value of this model, stating, “The company… has been investing in an integrated offer, bridging the problems of chemists and formulators all at the same shop.” To support this integration, the company continues to pioneer advanced manufacturing avenues, including continuous flow for drug substances and continuous tableting for drug products.

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

I’m Marcio Temtem. I'm currently vice president for strategic business management at Hovione. I've been in the company for 17 years. Hovione is a CDMO for pharmathat has been in the business for 66 years. Still a family-owned business that supports small molecule synthesis, production of drug product intermediates, and drug product, for pharma clients. First, and my answer will focus on the small molecule side, and I will try to cover three big trends. One of the trends that we see today is the increased complexity. Small molecules, they are not so small anymore. These days, they have come to a size and to a complexity, that require multiple chemical steps and that very often require high potency. They also require, on the formulation side of things, not just on the chemistry, but on the formulation side of things they also require a new toolbox. A new toolbox to address some of the challenges related with bioavailability. In our case at Hovione, we use a platform called amorphous solid dispersions, produced by spray drying to address this challenge of bioavailability. One other trend that we see happening as we speak relates with acceleration speed. I think it reach a different definition in 2025. There's a need to develop new molecules, new candidates at a faster pace. AI, it's booming all over the place, in the deployment of new molecules. And with this, new way of synthesizing molecules also comes complexity, bridging to what I said before. But it also requires companies like Hovione to develop the CMC section, to develop the process that will take the program from grams to tons at a much faster pace. So that's the second trend. The third trend is that there is an increased concern with the regionalization of the supply chains. You see a big trend in US for US, China for China. In our case, we look at this as an opportunity. Hovione has sites in three continents. In Asia, China, Macau, in Europe, Portugal, and Ireland, and the US. And we believe that, all these sites, they are FDA-inspected, I could say. And we believe that this is also an opportunity for Hovione to continue serving as it has been doing so far, all these markets. I would like to highlight two of our platforms. One of the platforms, I already touched before, that relates with the addressing solubility, bioavailability challenges through the making of amorphous solid dispersions. This is an area where Hovione has, today, the global leadership. And not just over 2025, but over the last years, we have been developing a number of tools, that allow to scale up the process, to develop the formulation with minimum use of API, and with a high probability of success. This is one element where innovation has played an important role to us in 2025. One other aspect to it is that the company, Hovione, has been investing in an integrated offer, bridging the problems of chemists and formulators all at the same shop. And when I say at the same shop, at the same site, which is something very, very unique in the CDMO environment. And in order to do so, we have also been developing new ways of manufacturing. I can tell you that, for instance, in the drug substance space, we have been exploring new avenues, such as, continuous flow, or on the drug product manufacturing, we have been exploring new ways of manufacturing, such as continuous targeting, in order to accelerate, in order to address some of these needs that clients today, bring to our shop.

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ACG Global Lighthouse Site | Image Credit: © CURIOS - stock.adobe.com

The designation of ACG’s Shirwal manufacturing facility as a global lighthouse by 

 marks a significant milestone in the pharmaceutical supply chain,¹ as it is the first time a pharmaceutical packaging company has been admitted into the Global Lighthouse Network. This recognition highlights a shift toward using smart manufacturing to improve the safety, sustainability, and affordability of medicines on a global scale. The designation marks the second accolade of this type for ACG, following the 2023 recognition of its Pithampur capsules manufacturing facility, reflecting the organization's sixty-year history as an integrated provider of oral dosage products and services, including barrier packaging and manufacturing machinery.

Karan Singh, managing director of ACG, stated in a press release,¹ “ACG has always believed that true leadership in the packaging sector comes from building smarter – not competing harder. Our Shirwal facility is now our second site to be recognised by the WEF’s Global Lighthouse Network, making ACG the world’s first pharmaceutical packaging company to receive this honour.” He added that “this achievement reflects the structures and frameworks we are putting in place across the Group. All ACG business entities are converging to optimise packaging so that medicines are safer, more sustainable, and more affordable. Repetition is the test of proof – in line with our ‘Make it Better’ commitment, we are replicating this Lighthouse excellence across our facilities and pioneering Sustainability Lighthouses for responsible, resilient manufacturing from India.”

How Does Digital Integration in Packaging Enhance Pharmaceutical Supply Chain Resilience?

In light of an increasing competitive and commoditized pharmaceutical packaging market, the digital transformation at the Shirwal facility was designed to improve productivity and quality while simultaneously reducing energy consumption.¹ The site integrates advanced technologies such as generative AI machine learning, deep learning, the industrial internet of things, and digital twin models.¹ By utilizing AI and these connected technologies, the facility has gained greater visibility into end-to-end manufacturing operations, which allows for more consistent responses to variations in production processes.

The operational impact of these digital initiatives is substantial, resulting in a 71% reduction in defects and a 40% reduction in lead times.¹ Furthermore, the facility recorded a 34% improvement in on-time delivery in full, as well as a 31% reduction in energy consumption. “This recognition reflects the commitment of our teams at Shirwal and their ability to integrate advanced digital technologies into everyday manufacturing operations. It strengthens our focus on delivering consistent quality, productivity and sustainability for customers worldwide,” claimed S R Shivshankar, CEO of ACG Packaging Materials, in an ACG press release.¹

Why Is the Adoption of Intelligence-Led Manufacturing Critical for the Future of Global Health?

The Global Lighthouse Network, a WEF initiative co-founded with McKinsey & Company, recognizes production sites that lead the way in productivity, sustainability, and customer centricity.¹ By driving technology-led transformation across the value chain, manufacturers can develop new business models and connected services that address modern industrial challenges. Balajikasiram Sundararajan, Chief Digital Officer of ACG Group, said in a press release,¹ “through our Build the Future programme, ACG is driving technology-led transformation across the manufacturing value chain, enabling smart manufacturing, connected products and services, and new business models. This prestigious Global Lighthouse recognition inspires us to continue scaling innovation across our businesses.”

As the industry moves continues to evolve, competitiveness is being redefined by a firm’s ability to predict and react to market trends. Kiva Allgood, head of the centre for advanced manufacturing and supply chains at the WEF, noted in the press release,¹ “competitiveness today is no longer defined by efficiency alone, but by the ability to sense, adapt and respond at speed. The Global Lighthouse Network showcases how intelligence-led operations are placing resilience and sustainability at the core of industrial performance.” For pharmaceutical companies operating across 138 countries, such advancements in packaging and production are essential for solving major health challenges and ensuring the reliable delivery of high-quality treatments.

How Else Is ACG Making Innovative Moves in 2026?

ACG recently announced their SuperPod system

, marking an important advancement in cold-form blister technology.² It addresses long-standing manufacturing limitations by enabling cavities to be up to 39% smaller while preventing aluminum rupture. This reduction optimizes material consumption and lowers logistics costs across the product lifecycle. Specialized multi-layer laminates now allow for deep-draw formations that can triple the number of blisters produced per shot, significantly increasing overall production capacity. Dr. Akbar Ali, general manager and head of development and technology at ACG Packaging Materials, commented in a press release,² “the technology effectively makes cold-form blisters lighter by reducing material usage per dosage. We see significant opportunities, particularly for high-count formats such as 20-count vitamins and B-complex capsules, where traditional cold-form blisters become impractically large.” Jochen Scheil, Vice President of Global Sales and Business Development, added in a press release.² “the launch of SuperPod™ encourages the industry to rethink decades-old design conventions and embrace smaller, smarter, and more sustainable blister formats.” These intelligence-led formats ensure that primary packaging remains an efficient and sustainable component of modern drug delivery.

ACG. ACG Packaging Materials Joins World Economic Forum’s Global Lighthouse Network as World’s First Pharmaceutical Packaging Company. Press Release. Feb 5, 2026.

ACG Packaging Materials Launches SuperPod™

ACG’s Shirwal site is the first pharmaceutical packaging site in the WEF Lighthouse Network, using digital tools to cut defects and boost sustainability.

WEF Welcomes ACG Shirwal as First Pharma Packaging Site in Global Lighthouse Network

FDA Approves New Breast Cancer Treatment | Created with Canva

FDA has accepted the supplemental Biologics License Application (sBLA) for AstraZeneca’s Datroway (datopotamab deruxtecan), granting it priority review for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for programmed death-ligand 1 (PD-L1) inhibitor therapy. Datroway could become the standard of care for a patient population where chemotherapy has long been the only approved option, according to the company.¹ FDA 

 for medicines that demonstrate the potential for significant improvements in safety or efficacy over existing treatments.

How Does this Regulatory Milestone Impact the Clinical Development Landscape?

Approximately 70% of patients with metastatic TNBC are ineligible for immunotherapy due to 

 or other limiting clinical factors. The sBLA is being reviewed under 

, an international framework that allows for the concurrent submission and review of oncology medicines among participating global partners. This collaborative regulatory path is intended to expedite the delivery of effective cancer treatments to patients by streamlining the review process across multiple jurisdictions.

Susan Galbraith, executive vice president, Oncology Haematology R&D, AstraZeneca, stated in a press release,¹ “Datroway is the only medicine to significantly improve overall survival compared to chemotherapy in this patient population as demonstrated in the TROPION-Breast02 trial–the results of which are even more striking considering the trial enrolled a subset of patients with highly aggressive disease. The Priority Review of our submission underscores the impact of these results and its review under Project Orbis signals a widely shared commitment to bringing Datroway to patients around the world as quickly as possible.”

A final regulatory decision under the Prescription Drug User Fee Act is anticipated during the second quarter of 2026.

What Clinical and Technical Advancements Support the Potential Approval of this Antibody Drug Conjugate?

Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) jointly 

 and Daiichi Sankyo. The drug consists of a humanized anti-TROP2 

 attached to topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers. In the TROPION-Breast02 Phase III trial,¹ Datroway demonstrated a statistically significant five-month improvement in median overall survival and a 43% reduction in the risk of disease progression or death compared to chemotherapy.

Daiichi Sankyo remains responsible for the global manufacturing and supply of the drug, which utilizes its proprietary DXd ADC technology.

Ken Takeshita, global head, R&D, Daiichi Sankyo, noted in a AstraZeneca press release that,¹ “Datroway potentially could be the first medicine approved in the 1st-line setting to significantly extend overall survival and nearly double the time without disease progression or death compared to chemotherapy in patients with metastatic triple-negative breast cancer for whom immunotherapy was not an option. We are eager to work with the FDA to bring this much needed treatment option to patients with metastatic triple-negative breast cancer.”

Beyond this specific indication, the clinical development program for this ADC now includes more than 20 trials across various solid tumors, reflecting a robust effort to expand the reach of this specialized delivery platform.

How Are Other AstraZeneca Medicines Progressing Through Approval Processes?

In Europe, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended durvalumab for adult patients with resectable, 

early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers

. This milestone highlights the expansion of immunotherapy into curative-intent settings where recurrence rates have historically remained high.² If approved, this would be the first immunotherapy-based perioperative regimen for this patient population in the EU.

How Does the Perioperative Regimen Alter the Current Clinical Path?

The regimen utilizes neoadjuvant durvalumab combined with FLOT chemotherapy, followed by adjuvant durvalumab with chemotherapy and subsequent monotherapy.

“Imfinzi plus FLOT demonstrated a durable, increasing long-term survival benefit in the MATTERHORN trial, with more than two-thirds of patients alive at three years. The CHMP recommendation marks further progress toward our goal to offer novel approaches in early-stage cancers where there is the greatest chance for cure and brings us closer to providing the third perioperative Imfinzi EU," Galbraith said in a press release.²

What Clinical Evidence Supports this Regulatory Advancement?

Data from the MATTERHORN Phase III trial indicated a 29% reduction in the risk of disease progression, recurrence, or death.

Josep Tabernero, MD, PhD, head of the Medical Oncology Department at Vall d'Hebron University Hospital, noted in a press release,² “This recommendation signals a major step forward for patients in the EU with early gastric and gastroesophageal junction cancers, who have historically faced high rates of recurrence and poor long-term outcomes despite curative-intent surgery and chemotherapy. This durvalumab-based perioperative regimen is the first immunotherapy approach to significantly extend survival in this setting, and if approved, should set a new standard of care.”

The safety profile of the combination remained consistent with known data for each medicine, and surgical completion rates were comparable to chemotherapy alone.

Datroway Granted Priority Review in the US As 1st-Line Treatment For Patients With Wetastatic Triple-Negative Breast Cancer Who Are Not Candidates For Immunotherapy

Imfinzi Perioperative Regimen Recommended For Approval in the EU By CHMP For Patients With Early Gastric and Gastroesophageal Cancers.

The FDA has accepted the supplemental Biologics License Application for Datroway, granting it Priority Review for first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) ineligible for PD-L1 inhibitor therapy. Datroway, a TROP2-directed DXd antibody drug conjugate, demonstrated significant improvements in overall survival in the TROPION-Breast02 trial. The application is reviewed under Project Orbis, expediting global regulatory processes. Concurrently, the European Medicines Agency recommended durvalumab for early-stage gastric cancers, marking a significant advancement in immunotherapy for curative-intent settings.

FDA has granted priority review to AstraZeneca's Datroway for the first-line treatment of metastatic TNBC treatment.

FDA Grants Priority Review to AZ's Datroway for Metastatic Triple Negative Breast Cancer

EMA recommends Kygevvi | Created with Canva

The first treatment for rare thymidine kinase 2 deficiency (TK2d), Kygevvi, a combination of doxecitine and doxribtimine, has been recommended by the European Medicines Agency (EMA) for marketing authorization. This represents a pivotal milestone in addressing a condition where there is no authorized treatment. This recommendation specifically applies to patients whose disease onset occurred at or before 12 years of age.¹ The clinical data indicate that Kygevvi improves motor function of patients that encounter symptoms in that age group.¹ To this point, clinical management for this population has been limited to supportive measures such as physiotherapy, enteral nutrition, and mechanical ventilation.

How Does the Therapeutic Mechanism Address the Underlying Genetic Pathology?

The pathology of thymidine kinase 2 deficiency, or TK2d, originates from mutations in the thymidine kinase 2 (TK2) gene, which prevent the TK2 enzyme from maintaining mitochondrial DNA. This enzymatic failure leads to progressive myopathy and significant loss of motor function. The EMA’s press release on the drug states,¹ “The way Kygevvi works in patients has not been confirmed, but studies in animal models suggest that its active substances, the pyrimidine nucleosides doxecitine and doxribtimine, are modified and incorporated into mitochondrial DNA in muscle cells, improving the production and maintenance of mitochondrial DNA.” By addressing this enzymatic shortfall, the treatment is expected to slow the progression of the disease. Common side effects observed during development include vomiting, abdominal pain, and diarrhea.

What Regulatory Pathways and Clinical Evidence Supported this Recommendation?

The EMA based its recommendation on a retrospective chart review alongside a phase 2 single arm clinical study involving 39 patients.¹ The results were significant for this small population, as 84% of patients regained at least one motor function. The authorization was recommended under exceptional circumstances because the rarity of the disease precludes the provision of full efficacy and safety data. This highlights the flexibility within the EU regulatory framework for orphan products. Consequently, the EMA has requested that the company perform a new study to further validate safety and efficacy post-authorization.

Development was further facilitated through the PRIority MEdicines scheme, which provides enhanced scientific support for medicines that address unmet needs. Having already received an orphan designation in 2017, the therapy will now be assessed by the Committee for Orphan Medicinal Products to determine if this status should be maintained.¹ Now that the Committee for Medicinal Products for Human Use has adopted this positive opinion, it moves to the European Commission for a final EU-wide decision. Subsequent steps for the manufacturer will involve member state-level negotiations regarding pricing and the medicine’s integration into individual national health systems.

How Does the Molecular Bypass Strategy Stabilize Mitochondrial Function?

The efficacy of this treatment strategy stems from its ability to bypass the genetic enzymatic defect by supplementing the deoxypyrimidine monophosphates that the body fails to produce. In a thymidine kinase 2 deficiency (TK2d) environment, the resulting imbalance in deoxynucleotide triphosphate pools leads to depleted mitochondrial DNA.² Research has demonstrated that oral supplementation effectively raises deoxythymidine triphosphate concentrations and restores mitochondrial DNA levels in various tissues. This biochemical directly ameliorates defects in mitochondrial respiratory chain enzymes, which are responsible for the severe neuromuscular manifestations associated with TK2d.

What Manufacturing and Metabolic Challenges Remain for Oral bypass Therapies?

While the treatment successfully crosses biological barriers, its longevity can be limited by metabolic catabolism. Evidence indicates that intestinal thymidine phosphorylase activity can increase over time, rapidly degrading the active substances before they reach systemic circulation.² This degradation reduces treatment efficacy, suggesting that future development may require formulation strategies to inhibit enzymatic breakdown or optimize delivery. Furthermore, the dose-related response observed in studies suggests that achieving precise, therapeutic concentrations is vital for maintaining mitochondrial DNA copy numbers.

First Treatment for Rare Thymidine Kinase 2 Deficiency

Garone, C., Garcia‐Diaz, B., Emmanuele, V. et al. 

Deoxypyrimidine Monophosphate Bypass Therapy for Thymidine Kinase 2 Deficiency

2014 6, 1016–1027. https://doi.org/10.15252/emmm.201404092

Kygevvi, a combination of doxecitine and doxribtimine, has been recommended by the EMA for treating thymidine kinase 2 deficiency (TK2d) in patients with disease onset at or before 12 years of age. This marks a significant advancement for a condition previously managed only with supportive care. The treatment aims to address the genetic pathology by supplementing deoxypyrimidine monophosphates, thereby stabilizing mitochondrial DNA. The EMA's recommendation is based on limited clinical data due to the disease's rarity, and further studies are required to confirm safety and efficacy.

EMA recommends Kygevvi for rare thymidine kinase 2 deficiency. It is the first authorized treatment for this disease.

EMA Recommends Kygevvi for Rare Thymidine Kinase 2 Deficiency Treatment

 has issued a recommendation for a conditional marketing authorization for Sanofi Winthrop Industrie’s Rezurock, also known as belumosudil, to treat chronic graft-versus-host disease. Chronic graft-versus-host disease is a long-term, life-threatening condition in which donor cells from stem cell or bone marrow transplants attack the recipient's body. The condition can affect 30% to 70% of adults and 6% to 33% of children receiving transplants for immunodeficiency syndromes or blood cancers.¹ The recommendation for Rezurock applies to adult and pediatric patients aged 12 and older who weigh at least 40 kilograms and have not found success with other therapies.

The current therapeutic landscape relies heavily on corticosteroids and other immune-suppressing agents, which often provide limited long-term benefit and carry the risk of severe side effects, such as low blood cell count, infection, and secondary cancer. Statistics show that approximately 50% to 75% of patients require multiple lines of therapy, yet second-and third-line options remain insufficient.¹ In the long term, roughly one-third of patients remain on treatment, while another one-third either die or experience a relapse of their original disease.

How Do the Regulatory and Clinical Requirements for Rezurock Influence the Pharmaceutical Development Pathway?

Rezurock functions as a protein kinase inhibitor that targets ROCK2, a protein involved in the immune reactions driving the disease. The product is formulated as a tablet for once-daily oral administration with food. The clinical data supporting this recommendation stem from an open-label study involving patients whose condition was inadequately controlled by 

 and at least two prior systemic therapies. In this study, 73% of patients responded to treatment within six months, with 44% maintaining that response at the six-month mark.¹ Specifically, 5% of patients achieved a complete response, meaning all symptoms in all affected organs resolved, while 68% achieved a partial, response meaning at least one organ improved and no other organ worsened or was affected.

The recommendation for a conditional marketing authorization is one of the EU regulatory mechanisms to facilitate early access to medicines that fulfill an unmet medical need. This pathway allows the agency to recommend a medicine with less complete data than is typically required if the benefit of immediate availability outweighs the inherent risks of incomplete data. Consequently, Sanofi Winthrop Industrie has committed to a confirmatory randomized controlled study to further validate efficacy.¹ Following the designation of Rezurock as an orphan medicine in 2019, the Committee for Orphan Medicinal Products will now evaluate whether this status should be maintained.

While common side effects such as nausea, diarrhea, fatigue, and elevated liver enzymes were reported,¹ the recommendation by 

the Committee for Medicinal Products for Human Use

 marks a critical intermediary step toward patient access. The final decision now rests with the European Commission, after which individual member states will determine pricing and reimbursement based on the medicine's role within their specific national health systems.

How else are Researchers Treating Graft-Versus-Host Disease?

While new treatments for established chronic graft-versus-host disease are emerging, researchers are also exploring prophylactic strategies to prevent the condition from developing initially.² Traditionally, prevention involves a medication regimen started immediately after hematopoietic stem cell transplantation. However, standard protocols often fail to prevent the chronic form of the disease, which significantly impairs long-term quality of life and return to work for survivors.

Recent clinical data suggest that a drug combination consisting of sirolimus, cyclosporine, and cyclophosphamide significantly reduces the incidence of moderate to severe chronic graft-versus-host disease compared with standard regimens.² This shift toward prevention addresses the disease before donor cells attack the recipient's body and cause potentially life-threatening organ damage. In phase II trials, only 3% of patients receiving this new combination developed the chronic condition, a significant reduction from the 33% seen with older drug combinations.

What Manufacturing and Clinical Considerations Arise From Multi-drug Prophylactic Regimens?

Managing these complex combinations requires careful consideration of immune balance. While the new regimen effectively prevented disease without increasing cancer relapse, it did increase the frequency of certain infections.² This highlights a manufacturing and clinical development challenge, balancing the immunosuppressive potency of agents like mammalian target of rapamycin inhibitors with the need to maintain infection-fighting capability. Future development will likely focus on large-scale, multicenter trials to ensure these results remain consistent across diverse patient groups.

New Medicine to Treat Chronic Graft-Versus-Host Disease

Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation

Sanofi Winthrop Industrie's Rezurock, a protein kinase inhibitor targeting ROCK2, has received a conditional marketing authorization recommendation from the EMA for treating chronic graft-versus-host disease in patients aged 12 and older. This condition affects a significant percentage of transplant recipients and is inadequately managed by current therapies. Rezurock showed promising results in an open-label study, with a 73% response rate. The recommendation allows early access to the drug, pending further validation. Additionally, new prophylactic strategies, including a sirolimus, cyclosporine, and cyclophosphamide combination, show promise in reducing disease incidence.

EMA recommends Rezurock (belumosudil) for chronic graft-versus-host disease, with the drug. Meetings unmet needs via conditional authorization.