dm+d

Unassigned

New Medicines

Haemophilia B

Information

New molecular entity
Pfizer
Pfizer

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes
Jul 18PIII development starts [3].
Nov 17Spark Therapeutics entered into an agreement with Pfizer to transfer the responsibility for development of Fidanacogene elaparvovec. Under the terms of the agreement Spark will be responsible for conducting all phase I/II studies while Pfizer will assume responsibility for pivotal studies, any regulatory approvals and potential global commercialization of the product [5]
Mar 17Granted access by EMA to the PRIME programme [2].
Nov 16Granted orphan drug status in US [2].
Jul 16Granted breakthrough therapy designation in US [2].

Category

An in vivo gene therapy, given as a single dose, that uses adeno-associated virus 8 (AAV8) vector to deliver the highly functional Padua variant of the FIX gene to liver cells, where it stimulates production of FIX that is 8 times more active than normal
Haemophilia B has a prevalence of around 1 in 30,000 live births (about five times rarer than haemophilia A). There are usually carrier females and affected males. The reference level of factor IX is 5 μg/mL but the normal range is from half to twice that level. Severe disease occurs with a factor IX level below 1% of the reference and accounts for about 50% of cases. Moderate severity occurs with a level of 1-5% and accounts for around 30% of cases [1].
Haemophilia B
Intravenous infusion

Trial or other data

Nov 20Collection of primary outcome data in PIII trial (NCT03587116) now expected to finish Jul 22. The PIII BENEGENE-2 trial which is evaluating the efficacy and safety of PF 06838435 in adult male participants with moderately severe to severe haemophilia B (participants that have a Factor IX circulating activity of 2% or less) is recruiting and due to complete collection of primary outcome data in May 22 [8].
Dec 19UK trial sites: NCT03587116 (Newcastle, Glasgow).
Aug 19PIII trial (NCT03587116) to establish a minimum of 6 months of prospective efficacy data of current FIX prophylaxis replacement therapy in the usual care setting of hemophilia B subjects, who are negative for nAb to AAV-Spark100, prior to the PIII study. is still recruiting with an estimated primary completion date of October 2021 [6].
Jul 19PIII BENEGENE-2 trial (NCT03861273) started with completion due Jul 2021 [7]
Jul 18PIII trial to evaluate efficacy and safety of fidanacogene elaparvovec for treatment of haemophilia B starts (NCT03587116). It will enrol approximately 110 patients in the US & aims to establish a minimum of 6 months of prospective efficacy data of current FIX prophylaxis replacement therapy in the usual care setting of hemophilia B subjects, who are negative for NAb to AAV-Spark100, prior to the PIII gene therapy study. Collection of primary outcome data is due to complete Nov 20 [4].
Dec 17Cumulative follow-up data from more than 13 patient years of observation in the PI/II GOLD-B trial showed consistent and sustained factor IX activity level with no serious adverse events in 11 patients. Spark and Pfizer also reported that up to four additional patients will be enrolled who will receive AAV8-hFIX19 manufactured using an enhanced process to test its comparability to the AAV8-hFIX19 received by the first 10 patients enrolled in the ongoing trial [2].
Jun 17Observational FIX-LONG study to evaluate long-term safety and efficacy of AAV8-hFIX19 in patients with haemophilia B and previously treated in the SPK-9001-101 protocol starts (NCT03307980) [2].
Dec 16Data from the PI/II (NCT01620801) study shows that a single dose of AAV8-hFIX19 in patients produced near normal levels of factor IX (30%), and thus clotting factor infusions were stopped [2].
Aug 15Pfizer, in collaboration with Spark, start the PI/II GOLD-B trial of AAV8-hFIX19, administered as IV infusion, in patients with haemophilia B (SPK-9001-101; NCT02484092). The non-randomised, open-label, dose-escalation trial is designed to enrol approximately 15 patients in the US [2].
Oct 12PI/II trial of an intravenously injected AAV8-hFIX19 in 15 adults with severe haemophilia B starts in the US and Australia (NCT01620801). Primary outcome measure is treatment-related adverse events after one year [2].