Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Fc fusion protein, Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfa, BIIB031, Elocta, Recombinant Factor VIII fusion protein
rFVIIIFc · 6 trials · 2 indications
AUCinf is area under the concentration-time curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥50 EDs to rFVIIIFc. In addition, the incidence for all participants, regardless of their EDs to rFVIIIFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.
An inhibitor test result greater than or equal to (\>=) 0.6 Bethesda units per milliliter (BU/mL), identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and by age cohort (\<6 years and 6 to \<12 years old) and treatment regimen for participants from 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.
| Arm | Type | Description |
|---|---|---|
| rFVIIIFc (15K scale) 1000 IU vial | EXPERIMENTAL | Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc (15K scale) 1000 IU vial at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 1000 IU vial. |
| rFVIIIFc (15K scale) 6000 IU vial | EXPERIMENTAL | Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc high strength vial (15K scale) at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 6000 IU vial. |
| rFVIIIFc | EXPERIMENTAL | Participants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (\>=) 50 exposure days (ED: 24-hour period in which \>=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (\>=5.00 Bethesda Units per milliliter \[BU/mL\]) or positive low titer inhibitor (\>=0.60 and \<5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding. |
| All participants | EXPERIMENTAL | PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated. Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated. |
| On-Demand | EXPERIMENTAL | The individual dose of rFVIIIFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor VIII (FVIII) levels. |
| Prophylaxis | EXPERIMENTAL | Tailored prophylaxis, Weekly prophylaxis or Personalized prophylaxis available. |
| rFVIIIFc 1000 / 3000 PK Assessment | EXPERIMENTAL | A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
| rFVIIIFc 3000 / 1000 PK Assessment | EXPERIMENTAL | A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. |
| A | EXPERIMENTAL | Cohort to receive a single low dose intravenous injection of commercially available rFVIII with safety and PK assessments followed by a single low dose intravenous injection of rFVIIIFc with safety and PK assessments |
| B | EXPERIMENTAL | Cohort to receive a single high dose intravenous injection of commercially available rFVIII with safety and PK assessments followed by a single high dose intravenous injection of rFVIIIFc with safety and PK assessments |
| Name | Type | Description |
|---|---|---|
| rFVIIIFc | BIOLOGICAL | As per arm description |
| BIIB031 (rFVIIIFc) | DRUG | Vials of rFVIIIFc were combined as needed, based on the actual labeled potency to achieve the participant's calculated dose. Partial vial use was allowed, in order to achieve the calculated dose. |
| FVIII (PK subgroup only) | DRUG | Baseline prestudy FVIII dosing in participants who enter the PK subgroup. Vials of prestudy FVIII were combined as needed, based on the nominal labeled potency (e.g., 250 IU, 500 IU, and 1000 IU), to achieve the participant's calculated dose. |
Key Inclusion Criteria: * Have severe hemophilia A, defined as \<1 IU/dL (\<1%) endogenous FVIII as determined by one-stage clotting assay from the central laboratory at Screening. * Previously treated subject, defined as having at least 150 documented prior exposure days (EDs) to any recombinant a...
Top 8 of 9 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Novo Nordisk A/S Sponsored ADR Class B | NVO | 15 | PHASE3 | Concizumab, Mim8, Denecimig, NNC0442-0344 A, turoctocog alfa pegol |
| Sanofi SA Sponsored ADR | SNY | 5 | PHASE3 | Fitusiran, efanesoctocog alfa |
| Pfizer Inc. | PFE | 8 | PHASE3 | Fidanacogene elaparvovec, Marstacimab |
| BioMarin Pharmaceutical Inc. | BMRN | 2 | PHASE3 | Valoctocogene roxaparvovec |
| Hoffmann-La Roche | RHHBY | 8 | PHASE3 | Emicizumab, NXT007, SPK-8011QQ, SPK-8011, SPK-8016 |
| Regeneron Pharmaceuticals, Inc. | REGN | 2 | PHASE1 | REGV131, LNP1265 |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 2 | PHASE1 | AskBio009 |
| Bayer | BAYRY | 6 | - | Damoctocog-alfa-pegol |
rFVIIIFc is used to prevent and treat bleeding episodes in people with hemophilia A, including severe hemophilia A. It is a replacement factor VIII protein studied in previously treated and previously untreated males with the condition. Development has focused on hemophilia A across multiple Phase 3 studies.
rFVIIIFc is developed by Sanofi, which trades under the ticker SNY. Sanofi is the sponsor behind the clinical program evaluating rFVIIIFc in hemophilia A, including long-term safety and efficacy studies and pharmacokinetic comparisons of different manufacturing scales and vial strengths.
rFVIIIFc has been studied in Phase 3 clinical development for hemophilia A, with additional Phase 1 pharmacokinetic work. The Phase 3 program includes trials in severe hemophilia A and in previously untreated males. It is an investigational product in clinical development rather than a newly approved therapy.
rFVIIIFc has been evaluated in completed trials including NCT01454739, a long-term safety and efficacy study in previously treated participants with hemophilia A; NCT02234323, in previously untreated males with severe hemophilia A; NCT02502149, comparing 15,000 L scale manufacturing; and NCT02083965, a Phase 1 pharmacokinetic study of two vial strengths.
Across the reported rFVIIIFc studies, total enrollment was 348 participants. The largest was NCT01454739 with 240 participants, followed by NCT02234323 with 108, NCT02502149 with 24, and the Phase 1 study NCT02083965 with 19. All enrolled participants were male.
The rFVIIIFc trials enrolled participants across many countries, including the United States, United Kingdom, Germany, France, Italy, Spain, Canada, Brazil, Japan, Australia, and New Zealand. The long-term study NCT01454739 had the broadest geographic reach, spanning more than twenty countries across North America, Europe, Asia, and Africa.