Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Fitusiran · 8 trials · 3 indications
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
Characterize the AT activity at the optimal therapeutic dose
The number of participants experiencing any TEAEs, serious TEAEs, discontinuation due to TEAEs and death will be reported
Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period\*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model.
A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period \*365.25.
ABR for a participant during efficacy period (EP) was defined as annualized number of bleeding episodes during EP annualized to a 1-year interval of time. Treated Bleeding episode: any occurrence of hemorrhage that required administration of by-passing agents (BPA) or factor. It started from first sign of a bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location or injections less than or equal to (\<=) 72 hours apart were considered the same bleeding episode. EP was defined as time duration starting from Day 29 when antithrombin (AT) lowering capacity of fitusiran had achieved therapeutic target range to the earliest of Day 246 or last day of bleeding follow up (maximum duration of EP: from Day 29 to Day 246). This outcome measure (OM) presents estimated results (i.e., results received by applying negative binomial \[NB\] regression model on data collected during EP).
ABR for a participant during EP was defined as annualized number of bleeding episodes during EP annualized to a 1-year interval of time. ABR= number of bleeding episodes during EP divided by total number of days during EP\*365.25. A bleeding episode was defined as any occurrence of hemorrhage that required administration of BPA or factor. It started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections \<=72 hours apart were considered the same bleeding episode. EP was defined as time duration starting from Day 29 when the AT lowering capacity of fitusiran had achieved therapeutic target range to the earliest of Day 246 or the last day of bleeding follow up (maximum duration of EP: from Day 29 to Day 246). This OM presents observed results (i.e., descriptive statistics values based on the data collected during EP).
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations \>3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis.
Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black.
Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m\^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin.
Urine samples collected to determine the significant abnormalities in urine.
Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline.
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds.
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
| Arm | Type | Description |
|---|---|---|
| Fitusiran-naïve arm | EXPERIMENTAL | Participants will go through a 24-week standard of care (SOC) period before receiving a selected dose of fitusiran at regular interval. If a fitusiran dose adjustment is needed during the study, participants will follow a specific dosing regimen as per study protocol. |
| EFC15647 roll-over arm | EXPERIMENTAL | Participants will continue receiving their current fitusiran dose from EFC15467. If a fitusiran dose adjustment is needed during the study, participants will follow a specific dosing regimen as per study protocol. |
| All participants | EXPERIMENTAL | In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine. . |
| Fitusiran | EXPERIMENTAL | Participants will receive a selected dose of fitusiran at regular intervals, as per study protocol |
| Factor On-demand | EXPERIMENTAL | Participants received on-demand factor concentrates (as needed, for episodic bleeding episodes, and not on a regular regimen intended to prevent spontaneous bleeding) per Investigator discretion for the treatment of breakthrough bleeding episodes from Day 1 up to a total of 9 months. |
| Fitusiran 80 mg Prophylaxis | EXPERIMENTAL | Participants received open-label fitusiran 80 milligram (mg) administered subcutaneously (SC) as prophylaxis once monthly from Day 1 up to a total of 9 months. Participants received on-demand factor concentrates (per investigator's discretion and within bleeding dosing guidelines) for the treatment of breakthrough bleeding episodes. |
| Bypassing Agents (BPA) On-demand | ACTIVE_COMPARATOR | Participants received On-demand BPAs (use of these agents, as needed, for episodic bleeding episodes, and not on a regular regimen intended to prevent spontaneous bleeding) per Investigator discretion from Day 1 for treatment of breakthrough bleeding episodes, up to a total of 9 months. |
| Name | Type | Description |
|---|---|---|
| Fitusiran | DRUG | Pharmaceutical form: solution for injection in PBS Route of administration: subcutaneous |
| Clotting factor concentrates (CFC) or bypassing agents (BPA) | BIOLOGICAL | Pharmaceutical form: solution for injection Route of administration: intravenous injection |
| Antithrombin concentrate (ATIIIC) | BIOLOGICAL | Pharmaceutical form: solution for injection Route of administration: intravenous injection |
| BPA prophylaxis | DRUG | Pharmaceutical form: solution for injection Route of administration: Intravenous |
| Factor (FVIII or FIX) prophylaxis | DRUG | Pharmaceutical form: solution for injection Route of administration: Intravenous |
| factor concentrates | DRUG | by intravenous (IV) injection |
| Bypassing agents | DRUG | solution for injection; by intravenous (IV) injection |
| Fitusiran (SAR439774) | DRUG | Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc) |
Inclusion Criteria: Participants not previously exposed to fitusiran are eligible to be included in the study only if all of the following criteria apply: * Participant must be 1 to \<12 years of age at the time of enrollment. * Participants must have severe hemophilia A or B (FVIII \<1% or FIX ≤2...
Fitusiran is an investigational small molecule being developed for the treatment of hemophilia, including hemophilia A. It is designed to prevent bleeding episodes in patients with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX. The drug is administered as a subcutaneous injection.
Fitusiran targets SERPINC1, which encodes antithrombin, a protein that inhibits blood clotting. By reducing antithrombin production through RNA interference, Fitusiran aims to promote thrombin generation and restore hemostasis in patients with hemophilia. This mechanism is classified as an RNAi inhibitor approach.
Fitusiran is being developed by Sanofi, a global biopharmaceutical company listed on the stock exchange under the ticker symbol SNY. Sanofi is conducting clinical trials to evaluate the safety and efficacy of Fitusiran in patients with hemophilia.
Fitusiran is currently in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Several Phase 3 trials are ongoing or completed, including studies in severe hemophilia A and B patients and a long-term safety and efficacy study.
Fitusiran has been studied in multiple clinical trials, including NCT03549871 (Phase 3, completed), NCT03754790 (Phase 3, active), NCT03974113 (Phase 2, active), and NCT05662319 (Phase 3, active). These trials enroll male patients with hemophilia, ranging from pediatric to adult populations, across numerous countries.
Fitusiran is sometimes referred to by its chemical name, fitusiran sodium, which is the salt form of the drug. In clinical trial records and scientific literature, the drug is commonly listed as fitusiran. Both names refer to the same investigational compound being developed by Sanofi for hemophilia.