Two gene therapies for hemophilia available: Now what?
Bibliographic record
Abstract
Hemophilia A and B (HemA, HemB) are X-linked recessive gene variants resulting in low or absent circulating active factor VIII (FVIII) or FIX, respectively. Their absence leads to delayed coagulation and attendant morbidity and mortality if bleeding episodes are untreated. Following two decades of development, the first gene therapies based on adeno-associated viral (AAV) vectors have recently received regulatory approval. The phase 3 data supporting conditional approval of valoctocogene roxaparvovec (Roctavian, for HemA) by the European Medicines Agency (EMA) and approval of etranacogene dezaparvovec (Hemgenix, for HemB) by the US Food and Drug Administration (FDA) have now been published. 1 Mahlangu J. Kaczmarek R. von Drygalski A. Shapiro S. Chou S.C. Ozelo M.C. Kenet G. Peyvandi F. Wang M. Madan B. et al. GENEr8-1 Trial GroupTwo-year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N. Engl. J. Med. 2023; 388: 694-705https://doi.org/10.1056/NEJMoa2211075 Crossref PubMed Scopus (26) Google Scholar ,2 Pipe S.W. Leebeek F.W.G. Recht M. Key N.S. Castaman G. Miesbach W. Lattimore S. Peerlinck K. Van der Valk P. Coppens M. et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N. Engl. J. Med. 2023; 388: 706-718https://doi.org/10.1056/NEJMoa2211644 Crossref PubMed Scopus (41) Google Scholar A closer look reveals not only new options but also complex new considerations for patients and providers making choices on their hemophilia therapies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.005 | 0.008 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.008 |
| Insufficient payload (model declined to judge) | 0.024 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".