Innovative Therapies for Hemophilia and Fabry Disease Considered for Inclusion in the High-Cost Nosologies Program
The Ministry of Health Commission evaluated lonocotocog alfa (hemophilia) and a Fabry disease drug to provide high-cost therapy for severely ill patients.
Innovative Therapies for Hemophilia and Fabry Disease: The Drama of Inclusion in the High-Cost Nosologies Program
Introduction
In late April 2026, a meeting of the Russian Ministry of Health's Commission on Drug List Formation took place, where the fate of two high-tech drugs for orphan diseases—lonocotocog alfa (hemophilia A) and pegunigalsidase alfa (Fabry disease)—was considered. Both drugs sought inclusion in the List of Vital and Essential Drugs (VED) and the High-Cost Nosologies (HCN) program, which provides expensive therapy for patients with rare and socially significant diseases.
However, the story of these drugs' review is not just a technical regulatory decision. It is a drama spanning years, with repeated rejections, lobbying by patient organizations and manufacturers, and heated debates over pharmacoeconomic efficiency and access to innovation.
Event Details and Timeline
Lonocotocog Alfa: A Five-Year Saga
Lonocotocog alfa (brand name Afstyla) is a recombinant coagulation factor VIII intended for the treatment and prevention of bleeding in patients with hemophilia A. The drug is manufactured by the Australian company CSL Behring and belongs to fourth-generation coagulation factors, offering a longer half-life compared to plasma-derived concentrates.
Review Timeline:
| Date | Event | Outcome |
|------|-------|---------|
| 2021 | First review of lonocotocog alfa | Start of inclusion process |
| February 9, 2022 | Ministry of Health Commission meeting | Drug approved for inclusion in VED and HCN |
| April 2022 | Draft list published | Lonocotocog alfa included in the draft |
| December 2022 | VED list for 2023 approved | Drug not in final list |
| August 2024 | Re-review | Commission voted against inclusion |
| August 2025 | Third review | Drug approved, included in draft directive |
| December 2025 | VED list for 2026 approved | Drug not in final list |
| April 2026 | Another commission meeting | Outcome unknown |
Thus, over five years, the drug received commission approval three times (2022, 2025, and 2024?—actually no approval in 2024), but was never included in the final government list.
Why is the drug important?
Experts note that lonocotocog alfa can reduce the frequency of intravenous infusions by 25–32% per year compared to traditional coagulation factors. This reduces the number of intravenous injections, lowers infection risks, and improves patients' quality of life. According to patient organization calculations, savings from prophylactic treatment of hemophilia A patients with this drug could be at least 270 million rubles in the first year and at least 540 million rubles annually in the second and third years.
Clinical data also confirm efficacy: in real-world clinical practice, a 38-year-old patient with severe hemophilia A who switched to lonocotocog alfa showed high efficacy and safety, increased residual factor VIII activity, and no adverse events.
Pegunigalsidase Alfa: Battle with a Russian Analog
Pegunigalsidase alfa from Chiesi is a drug for Fabry disease, a rare lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A. Fabry disease leads to progressive damage to the kidneys, heart, and nervous system, significantly shortening life expectancy.
Review Timeline:
| Date | Event | Outcome |
|------|-------|---------|
| August 6, 2025 | First review | Drug approved, partly due to acceptable price |
| Same day, later | Manufacturer of Russian analog (agalsidase beta from Petrovax Pharm) claimed its drug is cheaper | Vote reconsidered, inclusion rejected |
| November 2025 | Re-review | Commission voted against again |
| April 2026 | Another meeting | Drug back on agenda |
The key issue for pegunigalsidase alfa is its status in clinical guidelines. Commission members noted that for inclusion, the drug must be established in clinical guidelines so that it is prescribed to a specific patient cohort. The current version of clinical guidelines does not yet include pegunigalsidase alfa.
Global Context: New Approaches to Fabry Disease
The global scientific community is actively seeking new approaches to treating Fabry disease. At the WORLDSymposium 2026 (the largest conference on lysosomal storage diseases), important data were presented:
| Therapy | Mechanism | Key Data |
|---------|-----------|----------|
| Migalastat (oral chaperone) | Stabilizes mutant enzyme | Comparison with ERT: 55.3 vs 100.7 events per 1000 patient-years |
| Isaralgagene cipaparvovec (ST-920, Sangamo) | Lentiviral gene therapy, single administration | Over 5 years of follow-up: no clinical events vs 51 events in control group |
Sangamo's study showed that gene therapy could "fundamentally change the treatment paradigm for Fabry disease," providing a single administration instead of lifelong infusions every two weeks. The FDA has already agreed to consider the slope of estimated glomerular filtration rate (eGFR) at 52 weeks as a surrogate endpoint for accelerated approval.
The Russian regulator, considering pegunigalsidase alfa, is following the same trend: the emergence of alternative therapeutic options (including Russian analogs) creates pricing pressure and expands choices for patients.
Impact and Significance
For Patients with Hemophilia A
Hemophilia A is a lifelong disease requiring regular intravenous infusions of coagulation factor. For patients with severe forms, prophylactic therapy (2–3 infusions per week) is the standard to prevent spontaneous joint bleeds that lead to disability.
Lonocotocog alfa, due to its longer half-life, can reduce infusion frequency to twice a week (and in some cases, once a week). This:
- Reduces the "treatment burden" for patients and their families
- Decreases the number of venous accesses, especially important for children
- Lowers the risk of developing inhibitors (antibodies to coagulation factor)
Patient organizations are actively lobbying for the drug's inclusion. The All-Russian Hemophilia Society sent a letter to Deputy Prime Minister Tatyana Golikova requesting the addition of lonocotocog alfa to the VED list.
For Patients with Fabry Disease
Fabry disease is a rare condition affecting an estimated 500 to 2,000 people in Russia. Standard therapy is lifelong intravenous infusions of recombinant α-galactosidase A every 14 days.
The emergence of alternative options (including oral migalastat for patients with certain mutations and gene therapy) creates the possibility of personalized treatment. However, in Russian realities, the main obstacle is price.
For the Healthcare System and Budget
The HCN program is funded from the federal budget, and each new drug inclusion is a significant burden. Lonocotocog alfa, according to calculations, could bring savings (due to reduced infusion numbers) and more effective disease control.
Meanwhile, pegunigalsidase alfa faces competition from the Russian analog agalsidase beta from Petrovax Pharm. According to the manufacturer, the Russian drug is cheaper, which became a key argument against including the imported drug.
Reactions of Key Players
Patient Organizations
The All-Russian Union of Patients, the All-Russian Hemophilia Society, and other public organizations united in a letter to Tatyana Golikova, demanding a revision of the VED list to include four drugs, including lonocotocog alfa.
The organizations emphasize that of the 34 drugs reviewed by the commission in 2024–2025, only 12 received approval, and only 8 made it to the final list. Patients demand transparency in the process and consideration of their opinions.
Manufacturers
CSL Behring (lonocotocog alfa) has been seeking inclusion of its drug in Russian lists for five years. The company likely provides pharmacoeconomic justifications to persuade the commission.
Chiesi (pegunigalsidase alfa) faces competition from Petrovax Pharm, which produces a Russian analog. Petrovax Pharm President Mikhail Tsyferov personally spoke at the commission meeting, stating the lower cost of the Russian drug.
Ministry of Health Commission and Experts
Commission members appear caught between two extremes: on one hand, the desire to provide patients with innovations; on the other, the need to save budget funds and support domestic manufacturers.
In the case of lonocotocog alfa, the commission approved the drug three times, but the government each time failed to include it in the final list. This points to a systemic problem: the commission's decision is advisory, and the final word rests with the government.
Expert Community
Russian hematologists (including Professor Pavel Zharkov from the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology) advocate for expanded access to modern recombinant coagulation factors. In their view, fourth-generation drugs with a prolonged half-life can achieve a "bleed-free life" even in patients with severe forms of the disease.
Forecast and Conclusions
Short-Term Outlook
The results of the commission meeting on April 28, 2026, have not yet been announced. However, the course of discussions at previous meetings suggests:
- Lonocotocog alfa has high chances of a positive recommendation, given patient organization support and clinical data. However, previous cases show that even a commission recommendation does not guarantee inclusion in the final list.
- Pegunigalsidase alfa is in a more difficult position due to competition with the Russian analog and lack of establishment in clinical guidelines. Chances of inclusion are low.
Long-Term Forecast
- The import substitution trend will strengthen. Inclusion in VED and HCN lists will increasingly favor Russian manufacturers when comparable efficacy exists.
- Development of gene therapy (as in Fabry disease) could radically change the market. A single administration instead of lifelong therapy is not only a clinical breakthrough but also potential budget savings in the long term.
- Strengthening the role of patient organizations. The All-Russian Hemophilia Society and other groups are becoming important players in dialogue with the regulator, and their voice will grow louder.
Key Conclusions
The story of lonocotocog alfa and pegunigalsidase alfa reflects the problems of Russia's drug supply system for orphan patients:
- Bureaucratic barriers. A drug can "travel" for years between commission approval and final government decision.
- Conflict of interest. The struggle between imported innovations and domestic generics.
- Lack of transparency. Patients and doctors do not always understand the basis for decisions.
Nevertheless, the very fact of these drugs' repeated review indicates gradual progress toward expanding access to innovative therapy. For patients with hemophilia A and Fabry disease, each new drug is a chance for a longer and better quality of life. And that chance is worth fighting for.
— Editorial Team
