dm+d

Unassigned

New Medicines

JiviHaemophilia A - prophylaxis and treatment

Information

Jivi
New formulation
Bayer
Bayer

Development and Regulatory status

Licensed but not launched
Launched
Licensed but not launched
Yes
Mar 20Company has no plans to launch in UK [18].
Aug 19Launched in Greece [17].
Nov 18Approved in the EU [16].
Sep 18Recommended for EU approval by CHMP - the full indication is "Treatment and prophylaxis of bleeding in previously treated patients ≥ 12 years of age with haemophilia A (congenital factor VIII deficiency).” It is proposed that it be prescribed by physicians experienced in the treatment of haemophilia [15].
Aug 18Approved by the FDA [14].
Oct 17Filed in EU via centralised procedure [13].
Aug 17Filed in US with data from the Protect VIII trial [12].
Oct 15PIII development continues [10].
Feb 14Plans to file in EU and US 2nd quarter of 2015 [7].
Feb 11Granted orphan drug status in the EU (EU/3/10/847) [3].

Category

BAY94-9027 has been designed to extend the circulating half-life of rFVIII through site specific attachment of a polyethylene glycol (PEG) polymer to the light chain of the rFVIII molecule, while preserving its full biologic activity.
haemophilia A affects ~0.6 in 10,000 people in the EU, equivalent to ~30,000 people [3].
Haemophilia A - prophylaxis and treatment
Intravenous infusion

Trial or other data

Nov 16Bayer plans an observational clinical trial for Haemophilia A in USA, France, Austria, Israel and Netherlands (NCT02971930) [11].
Jan 15Detailed results from the PIII PROTECT VIII trial (NCT01580293) available. The primary endpoint of the study was annualised total number of bleeds and 143 pts were allocated to one of four arms. Pts (n=43) in the 1st received infusion every five days and 44% experienced no bleeds with a median annualised bleeding rate (ABR) of 1.9. Pts in the 2nd arm (n = 43) received infusion every seven days, 37% experienced no bleeds with median ABR of 3.9. Pts in the 3rd arm (n = 13) received infusion twice a week which reduced their ABR from 17.4 to 1.4. Pts in the 4th arm (n=20) received on-demand treatment with median ABR of 23. In addition, Bayer reported that a subgroup analysis of the trial demonstrated improved bleeding protection in patients receiving damoctocog alfa pegol prophylaxis dosing based on bleeding phenotype compared to prestudy levels, highlighting the importance of phenotype-guided dosing.Damoctocog alfa pegol was generally well tolerated but hypersensitivity reactions were reported in two pts. One was reported as serious adverse event. The estimated study completion date is currently February 2017 [8,9].
Feb 14The PIII PROTECT VIII trial met its primary objective of protection from bleeds with fewer infusions. In the study, the site-specific PEGylated factor VIII provided protection from bleeds when used prophylactically every seven days, every five days, and twice per week. It was also effective for treatment of acute and breakthrough bleeds with 91% of events resolved with one or two infusions [7].
Jul 13Bayer has started to enrol children in an international PIII PROTECT VIII Kids trial to investigate whether BAY 94-9027, at different dosing frequencies, can be used prophylactically to prolong duration of protection from bleeding events for up to one week, while also being used to treat acute bleeds. The multicentre, multinational, partially randomized, open-label trial will enrol 50 previously treated patients (aged up to 12 years) worldwide, who have severe haemophilia A (<1% FVIIIc) and a documented history of at least 50 exposure days with any FVIII product. Subjects who are currently treated with primary or secondary prophylaxis or are not receiving a regularly prescribed infusion regimen (on-demand or intermittent prophylaxis) may be enrolled. The total duration of the individual treatment is 50 exposure days. An optional extension study will collect observations for at least 50 additional exposure days [6].
Jul 13Enrollment started in PII/III open-label, non-controlled study, PROTECT VIII (NCT01580293), to evaluate BAY94-9027 for treating haemophilia A in 50 male children <12yrs, when used as prophylaxis, dosed at least once weekly and on-demand for acute bleeding. Outcome measures to be evaluated include pharmacokinetics, annualised bleeding episodes, response of acute bleeding episodes to treatment and adverse events, including inhibitor formation. The total duration of the individual treatment with the study drug is the amount of time required to achieve at least 50 exposure days [5].
Apr 13NCT01775618 is a multi-centre, PIII, non-controlled, open-label trial of BAY94-9027 for prophylaxis and treatment of bleeding in 50 previously treated children (age <12 years) with severe haemophilia A. Primary outcomes are annualised numbers of bleeds and pharmacokinetic profile. The study starts May 13 and is due to complete Feb 16 (primary data available Mar 15) [4].
Jul 12Bayer has started to enroll patients 120-140 previously treated patients with haemophilia A in an international, partially randomised PII/III study (NCT01580293). The PROTECT VIII (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII) trial will investigate whether BAY94-9027 can prolong the duration of protection from bleeds and with less frequent Infusions when used prophylactically, while also having the ability to treat acute bleeding events. The study is due to complete Dec 13 [1,2].

Evidence based evaluations