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Knowledge
Gene therapy for hemophilia: documentation and collaboration between centers

Which therapies are approved, how hub and spoke work together, what the G-BA requires and why follow-up lasts 15 years.

Two gene therapies for hemophilia have been conditionally approved in the EU: Roctavian for hemophilia A in August 2022 and Hemgenix for hemophilia B in February 2023. Since February 2026 the manufacturer BioMarin has been voluntarily withdrawing Roctavian from the market, with continued follow-up for patients already treated; Hemgenix remains available. In Germany, only centers that meet the requirements of the G-BA’s ATMP quality assurance directive may treat; treatment with Hemgenix is additionally tied to documentation in the German Hemophilia Registry. Care follows the hub-and-spoke model: a specialized center administers the single infusion, the home center counsels the patient and provides follow-up care, which lasts at least 15 years. Shared, structured documentation across center boundaries thus becomes the core task.

Legal status: September 2026

What gene therapy changes

The approved gene therapies use an adeno-associated virus vector (AAV) to deliver a functional copy of the factor VIII or factor IX gene into liver cells. A single infusion replaces regular factor administration; how high the achieved factor activity is and how long it lasts varies from patient to patient. Two products are conditionally approved in the EU: Roctavian (valoctocogene roxaparvovec) since August 24, 2022 for adults with severe hemophilia A without a history of factor VIII inhibitors and without detectable antibodies to AAV51, and Hemgenix (etranacogene dezaparvovec) since February 20, 2023 for adults with severe or moderately severe hemophilia B without a history of factor IX inhibitors.2 A third product for hemophilia B, Beqvez (fidanacogene elaparvovec), was approved in July 2024 and withdrawn in May 2025 at the manufacturer’s request for commercial reasons, without ever having been marketed.3 Roctavian, too, is no longer available: on February 23, 2026, BioMarin announced it would voluntarily remove the product from the market after failing to find a buyer – expressly not for reasons of efficacy or safety. Patients already treated are to receive continued monitoring and follow-up care.13 Of three approved gene therapies in Europe, one remains.

For documentation, the task changes. Factor therapy is a chain of similar administrations, each documented individually; gene therapy is a one-time intervention with a history of eligibility assessments, a closely monitored early phase and follow-up over decades. Liver values must be checked closely in the first months, corticosteroids are often needed, and factor activity is measured continuously to decide whether and when prophylaxis is resumed. At least two centers are involved, and the same data are needed for clinical care, the registry, the benefit assessment and the obligations of the marketing authorization.

Who does what: roles in the hub-and-spoke model

In 2020, EAHAD and EHC recommended that all first-generation gene therapies be managed using a hub-and-spoke model; in 2023 the GTH elaborated the model for Germany, Austria and Switzerland, and the G-BA made the requirements for treating facilities binding. The table summarizes the roles.

WhoWhatBasisPeriod
Gene therapy center (“hub”) Prescribes and administers the gene therapy: eligibility assessment (inhibitor history, for Roctavian antibodies to AAV5, liver health, psychosocial suitability for lifelong follow-up), counseling together with the home center, infusion, management of the early phase with liver values and corticosteroids. Requirements under the G-BA: at least 30 cases of severe hemophilia treated in the previous year, specialist qualification in hemostaseology, access to gastroenterology, standardized procedures for selection, consent, treatment and documentation. EAHAD/EHC 20204, GTH 20235, G-BA ATMP quality directive6 Preparation through the end of the early phase, then contact person around the clock
Home center (“spoke”) Counsels the patient as part of informed decision-making, refers to the hub, provides local follow-up care with regular checks of factor activity, liver values and bleeds, and reports findings back to the hub. EAHAD/EHC 20204, GTH 20235 Follow-up for at least 15 years
Patient Carries an identity card naming the supervising gene therapy center and a contact person reachable around the clock, continues to document bleeds and any factor administrations, and answers quality-of-life questionnaires for registries and studies. EAHAD/EHC 20204; for factor administrations still Section 14 TFG ongoing
Treating physicians towards the registry Document the gene therapy in the German Hemophilia Registry. For Hemgenix, the G-BA’s mandatory data collection has been running there as a registry study since August 30, 2024; only physicians who document there may treat. For Roctavian, the same requirement applied from August 30, 2024 to April 2, 2026. Section 35a (3b) SGB V, G-BA decisions7, 8; Section 21a TFG11 Hemgenix: interim reviews until 2029, final report 2029
Manufacturers Provide the EMA, as a condition of the conditional approval, with long-term safety and efficacy data from ongoing studies and from registries of treated patients, for example the GENEr8-COAS registry study for Roctavian. Follow-up of patients already treated continues even after a market withdrawal; BioMarin has committed to this for Roctavian. Obligations of the conditional marketing authorization1, 2; BioMarin 202613 until the obligations are fulfilled, regardless of marketing

The treatment pathway in seven steps

This is how a gene therapy proceeds in the hub-and-spoke model. Each step generates data that more than one center needs.

  1. Counseling at the home center: is gene therapy an option, what are the alternatives, what does the patient expect?
  2. Eligibility assessment at the gene therapy center: inhibitor history, for Roctavian antibodies to AAV5, liver health without advanced fibrosis, cirrhosis or uncontrolled infection, psychosocial suitability for lifelong follow-up.
  3. Joint decision by patient, home center and gene therapy center, counseling and consent; the basis for the decision is documented.
  4. Single infusion at the gene therapy center; report to the German Hemophilia Registry, for Hemgenix as part of the registry study.
  5. Early phase: close monitoring of liver values, corticosteroids if needed, measurement of factor activity; decision whether prophylaxis is continued or stopped (for Hemgenix at least three months of observation).
  6. Follow-up at the home center: factor activity, bleeds, liver values, quality of life; feedback to the gene therapy center.
  7. Long-term follow-up over at least 15 years with reports to the registry, manufacturers’ data deliveries to the EMA and contributions to international registries.

Two centers share one patient record – and without a shared platform that means fax, physician letters and binders. The GTH therefore explicitly recommends an electronic platform for secure and timely data exchange between the centers and the patients, which also serves as the primary data source for pharmacovigilance, studies, national and international registries and for the early benefit assessment.5

The benefit assessment is the second reason for complete documentation. The G-BA could not quantify an added benefit for either gene therapy and therefore ordered mandatory data collection, which has been running as a registry study in the German Hemophilia Registry since August 30, 2024. For Roctavian, the G-BA terminated it on April 2, 2026 because the manufacturer submitted neither a revised study protocol nor interim analyses; the restriction on who may prescribe was lifted as a result. For Hemgenix, the data collection continues with interim reviews until 2029.7, 8

Registries and follow-up

Since its relaunch in 2019, the German Hemophilia Registry has also captured innovative therapies including gene therapy; centers report on the basis of Section 21a TFG.11 Internationally, the World Federation of Hemophilia’s Gene Therapy Registry collects long-term data on the safety, efficacy and durability of gene therapies, supported by ISTH, EAHAD, EHC and the US patient organization; centers report directly or via national registries, and patients report their quality of life through the myGTR tool, quarterly at first and then twice a year.10

How long follow-up lasts is governed at two levels. In its guideline on the follow-up of patients administered gene therapy, the EMA requires, for vectors without genomic integration, checks at 3, 6 and 12 months and then annually for at least five years, longer if there are indications of risk.9 The G-BA goes further: treating facilities in Germany must ensure structured follow-up care over at least 15 years.6 Added to this are the obligations of the conditional approvals, which commit the manufacturers to long-term data from studies and registries.1, 2

What this means for documentation

The same treatment is needed in five places: in the gene therapy center’s record, in the home center’s record, in the German Hemophilia Registry, in the G-BA’s registry study and in the manufacturers’ data deliveries to the EMA. Anyone who serves each place separately records the same liver value several times and risks the versions drifting apart. Documentation must therefore be created once and be exportable many times.

The scope is larger than in factor therapy: checklists for eligibility criteria and tasks per treatment phase, cooperation agreements and contracts between the centers, consents, physician letters, laboratory histories over years, bleeds and factor administrations from the patient diary, quality-of-life questionnaires. And it must remain readable and attributable for 15 years, even when physicians change, centers are restructured or a product leaves the market.

As the examples show, registry obligations, prescribing authorizations and product availability change within a few years: Beqvez returned its authorization after ten months; for Roctavian, first the G-BA’s registry study ended and then its marketing. The treated patients remain, and with them 15 years of follow-up. A documentation system for gene therapy must be able to reflect such changes without rendering the histories already recorded unusable – and it must not be tied to a manufacturer that leaves the market.

What digital tools must deliver

  • A structured treatment process in sections, from eligibility assessment through decision, infusion and early phase to follow-up, with checklists that reflect the requirements of the G-BA, GTH, EMA and registries.
  • A shared record for hub and spoke with clear roles and rights, encrypted transfer between the centers and secure communication within the application instead of fax and e-mail.
  • Laboratory histories and follow-up data over years, with factor activity, liver values and bleeds over time.
  • Outputs for registries and studies: German Hemophilia Registry, G-BA registry studies, manufacturer registries, international registries – from one data set.
  • An interface to the patient’s electronic diary, so that bleeds and factor administrations from home treatment reach the record without re-entry.
  • Materials for patient counseling such as brochures, checklists and videos at the point in the process where they are needed.
  • Manufacturer independence, because several products coexist and approvals change.
  • Availability for at least 15 years with data storage in Germany and exportability.

How smart medication maps gene therapy

smart medication Gene is a collaboration platform with an electronic patient record for gene therapy in hemophilia A and B that implements the hub-and-spoke model in software: the treatment process is laid out in sections with checklists, developed together with hemostaseologists, pharmaceutical manufacturers and pharmacists; hub and spoke work in a shared record with encrypted transfer and secure in-app communication; laboratory results, follow-up data, contracts, consents and physician letters are stored in structured center and patient records. The application is manufacturer-independent and sponsored by BioMarin and CSL Behring.12

Via an interface, the treatment history from smart medication eDiary flows into the record, so that bleeds and factor administrations from home treatment do not have to be entered again. The documentation duties of factor therapy, which continue alongside gene therapy, are described on the knowledge page Digital documentation in hemophilia care.

Frequently asked questions

Which gene therapies for hemophilia are approved and available in the EU?
Conditionally approved were Roctavian (valoctocogene roxaparvovec) on August 24, 2022 for adults with severe hemophilia A without a history of factor VIII inhibitors and without antibodies to AAV5, and Hemgenix (etranacogene dezaparvovec) on February 20, 2023 for adults with severe or moderately severe hemophilia B without a history of factor IX inhibitors. As of September 2026 only Hemgenix is available: BioMarin has been voluntarily withdrawing Roctavian from the market since February 2026, and Beqvez (fidanacogene elaparvovec) was approved in 2024 and withdrawn in 2025 at the manufacturer’s request.
Who may perform gene therapy for hemophilia in Germany?
Only facilities that meet the requirements of the G-BA’s ATMP quality assurance directive of December 21, 2023: at least 30 cases of severe hemophilia treated in the previous year, responsible physicians with a qualification in hemostaseology, access to gastroenterology, standardized procedures and structured follow-up care over at least 15 years. Authorization is granted by the regional association of statutory health insurance physicians or the Medical Service. For Hemgenix, in addition: only physicians who document the treatment in the German Hemophilia Registry.
What is the hub-and-spoke model?
A care model proposed by EAHAD and EHC in 2020: specialized centers with experience in gene therapy (“hubs”) prescribe and administer the treatment; the patients’ home centers (“spokes”) counsel, refer and provide follow-up care in close coordination with the hub. In 2023, the GTH specified the model in its recommendation for Germany, Austria and Switzerland.
How long does follow-up last after gene therapy?
In Germany at least 15 years; the G-BA requires this of the treating facilities. The EMA guideline on follow-up provides, for vectors without genomic integration, for checks at 3, 6 and 12 months and then annually for at least five years, longer if there are indications of risk. In addition, the conditional approvals impose long-term obligations on the manufacturers.
What is the mandatory data collection, and does it still apply?
A registry study ordered by the G-BA under Section 35a (3b) SGB V to reassess the added benefit. It has been running in the German Hemophilia Registry since August 30, 2024. For Hemgenix it continues, with interim reviews until 2029; only documenting physicians may treat. For Roctavian, the G-BA terminated the collection on April 2, 2026 because the manufacturer did not deliver the protocol and interim analyses; the prescribing restriction has thus lapsed.
Does a patient have to keep documenting after gene therapy?
Yes. Bleeds remain the central measure of success and belong in the follow-up; if factor products are administered, for example for procedures or when factor activity declines, the documentation duty under Section 14 TFG applies unchanged. Quality-of-life questionnaires for registries and studies are added. EAHAD and EHC also recommend an identity card naming the supervising gene therapy center and a contact person reachable around the clock.
Which data does the gene therapy center need from the home center and vice versa?
Before treatment: medical history, inhibitor status, bleeding history and factor consumption from the diary, liver findings. Afterwards: laboratory histories with factor activity and liver values, bleeds, medication including corticosteroids, adverse events, quality of life. Both centers need the same status at all times, which is why the GTH recommends a shared electronic platform.
Why are Beqvez and Roctavian off the market, and what does that mean for documentation?
Pfizer had the authorization for Beqvez withdrawn in May 2025 for commercial reasons; the product was never marketed in the EU. On February 23, 2026, BioMarin announced it would voluntarily withdraw Roctavian from the market because no buyer could be found for the product – not for reasons of efficacy or safety. For patients already treated, nothing changes in follow-up care and long-term observation; BioMarin has committed to continued support, and the G-BA’s 15 years continue to run. For documentation, both cases show that products come and go while patients’ histories remain. A documentation system must be manufacturer-independent and reflect changes without rendering recorded histories unusable.

Glossary

AAV
Adeno-associated virus; as a vector it carries the therapeutic gene into the liver cells. Roctavian and Hemgenix use serotype AAV5. Pre-existing antibodies to AAV5 exclude treatment with Roctavian.
Vector
The delivery vehicle for the gene, here a virus that does not integrate into the genome. This determines how long the EMA requires follow-up.
Factor activity
The activity of factor VIII or IX measured in blood as a percentage of normal; after gene therapy the most important measure of effect and durability.
Hub
Gene therapy center: specialized hemophilia center that prescribes and administers the gene therapy and manages the early phase.
Spoke
The patient’s home center, which counsels, refers and provides long-term follow-up care.
ATMP
Advanced therapy medicinal products, including gene therapies.
ATMP quality directive (ATMP-QS-RL)
G-BA directive on quality assurance in the use of ATMPs; the annex for gene therapy in hemophilia has applied since the decision of December 21, 2023.
Mandatory data collection (AbD)
Data collection in routine care ordered by the G-BA under Section 35a (3b) SGB V, here as a registry study in the German Hemophilia Registry; basis for a renewed benefit assessment.
Conditional marketing authorization
EMA approval in the case of unmet medical need on the basis of still incomplete data, combined with the obligation to provide further data.
EAHAD, EHC
European Association for Haemophilia and Allied Disorders (professional society) and European Haemophilia Consortium (patient organization); authors of the hub-and-spoke statement.
GTH
Society of Thrombosis and Haemostasis Research; its recommendation on gene therapy for hemophilia appeared in Hämostaseologie in 2023.
WFH GTR
Gene Therapy Registry of the World Federation of Hemophilia, an international long-term registry; myGTR is the part in which patients report themselves.
Inhibitor
Antibodies against the administered clotting factor. A history of inhibitors excludes the approved gene therapies.

Sources (largely in German)

  1. European Medicines Agency (EMA): Roctavian (valoctocogene roxaparvovec), product information and authorization overview – conditional approval August 24, 2022, indication, exclusion criteria, obligations including the GENEr8-COAS registry study. www.ema.europa.eu/en/medicines/human/EPAR/roctavian, opens in a new tab
  2. EMA: Hemgenix (etranacogene dezaparvovec) – conditional approval February 20, 2023, indication, observation for at least three months, obligations including a patient registry. www.ema.europa.eu/en/medicines/human/EPAR/hemgenix, opens in a new tab
  3. EMA: Beqvez (fidanacogene elaparvovec) – approval July 24, 2024, withdrawal of the authorization by the European Commission on May 15, 2025 at the manufacturer’s request. www.ema.europa.eu/en/medicines/human/EPAR/durveqtix, opens in a new tab
  4. EAHAD and EHC: Statement on promoting the hub-and-spoke model when using gene therapies, May 2020. eahad.org/eahad-ehc-statement-on-promoting-hub-and-spoke-model-using-gene-therapies/, opens in a new tab
  5. Miesbach W., Oldenburg J., Klamroth R., Eichler H. et al.: Gene therapy of hemophilia: recommendations of the Society of Thrombosis and Haemostasis Research (GTH). Hämostaseologie 2023; 43(3): 196–207 (in German). doi.org/10.1055/a-1957-4477, opens in a new tab
  6. Federal Joint Committee (G-BA): ATMP – quality rules for gene therapies in the treatment of hemophilia, decision of December 21, 2023 (at least 30 cases of severe hemophilia in the previous year, follow-up for at least 15 years). www.g-ba.de/service/fachnews/107/, opens in a new tab
  7. G-BA: Mandatory data collection for gene therapies in the treatment of hemophilia from August 30, 2024; procedure page for Hemgenix with interim reviews until 2029. www.g-ba.de/service/fachnews/139/, opens in a new tab · www.g-ba.de/studien/abd/hemgenix/, opens in a new tab
  8. G-BA: Valoctocogene roxaparvovec – mandatory data collection terminated, decision of April 2, 2026. www.g-ba.de/service/fachnews/241/, opens in a new tab
  9. EMA: Guideline on follow-up of patients administered with gene therapy medicinal products (EMEA/CHMP/GTWP/60436/2007), in force since May 1, 2010. www.ema.europa.eu/en/follow-patients-administered-gene-therapy-medicinal-products-scientific-guideline, opens in a new tab
  10. World Federation of Hemophilia: Gene Therapy Registry (GTR) and myGTR. wfh.org/research-and-data-collection/gene-therapy-registry/, opens in a new tab
  11. Paul-Ehrlich-Institut: German Hemophilia Registry (DHR), legal basis Section 21a TFG; press release on the 2019 relaunch with capture of innovative therapies including gene therapy. www.pei.de/DE/regulation/melden/dhr/dhr-node.html, opens in a new tab · www.pei.de/DE/newsroom/pm/jahr/2019/16-neues-deutsches-haemophilieregister-dhr-geht-online.html, opens in a new tab
  12. Grätzel von Grätz P.: Gentherapie startet, IT-Lösung hilft. E-HEALTH-COM, March 30, 2023. e-health-com.de/details-news/gentherapie-startet-it-loesung-hilft/, opens in a new tab
  13. BioMarin: BioMarin Voluntarily Withdraws ROCTAVIAN from the Market. Company statement of February 23, 2026 – withdrawal after an unsuccessful search for a buyer, not for reasons of efficacy or safety; commitment to continued follow-up of treated patients. www.biomarin.com/news/company-statements/biomarin-voluntarily-withdraws-roctavian-from-the-market/, opens in a new tab