Severe haemophilia A in males
Advanced therapy medicinal product (ATMP)
Development and Regulatory status
Feb 20 · The FDA has accepted for Priority Review the Biologics License Application (BLA) for AAV5 gene therapy valoctocogene roxaparvovec, for adults with hemophilia A. The PDUFA action date is August 21, 2020 .
Feb 20 · Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 .
Dec 19 · Filed in the US, with a decision expected Feb 20. In the EU, The EMA granted valocotogene access to its Priority Medicines (PRIME) regulatory initiative in 2017 and recently granted accelerated assessment of the MAA, potentially shortening the review period, with a decision expected in Jan 20 .
Nov 19 · BioMarin has submitted a MAA to the European Medicines Agency for its investigational gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A .
Aug 19 · BioMarin plans to submit an accelerated approval request to the FDA and to the EMA during Q4 2019 .
May 19 · BioMarin aims to meet with FDA and EMA to review the data with plans to submit marketing applications in Q3 2019.
Oct 17 · valoctocogene roxaparvovec (previously BMN270) granted Breakthrough Therapy designation by the FDA based on data from ongoing PI/II trials. Protocols for PIII studies have been submitted to and approved by both the FDA and the MHRA. US PIII studies are expected to start after approval from institutional review boards .
Apr 17 · Biomarin plans to commence PIII study in Q3 17 .
Feb 17 · Granted PRIME status in the EU. Has orphan drugs status in the EU & US .
A gene therapy, designated as BMN 270, to stimulate the production of factor VIII, a blood coagulation factor, for the treatment of haemophilia A.
It affects 1:4,000 to 1:5,000 live male births worldwide .
Severe haemophilia A in males
Has been prioritised
Trial or other data
Apr 20 · Valoctocogene has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise 
Jan 20 · PIII BMN 270-302 study (NCT03392974) is ongoing to confirm the safety and effectiveness of the 4E13 vg/kg dose of valoctocogene roxaparvovec. 40 adults will be recruited .
Jan 20 · PIII BMN 270-301 study (NCT03370913) is ongoing to confirm the safety and effectiveness of the 6E13 vg/kg dose of valoctocogene roxaparvovec. 134 adults have been recruited .
Jan 20 · NCT02576795 - UK trial sites (Hampshire, Birmingham, Bristol, Cambridge, Glasgow, Barts, Guy´s, Imperial, Southampton) 
Jan 20 · Follow up data published showed sustained, clinically relevant benefit, as measured by a substantial reduction in annualized rates of bleeding events and complete cessation of prophylactic factor VIII use in all participants who had received 4×1013 vg per kilogram or 6×1013 vg per kilogram of the gene therapy. 
May 19 · Positive PIII clinical trial results announced for valoctocogene roxaparvovec in adults with hemophilia A. Eight out of 20 pts in the GENEr8-1 study showed Factor VIII levels of 40 IU/dL or more at 23-26 wks (which was the pre-specified criteria for Factor VIII activity levels). Of the 16 pts who made it to week 26 by the April 30 cutoff, the estimated median Annual Bleed Rate (ABR) was zero and the estimated ABR was 1.5. This comes to a decrease of 85% from baseline levels where all pts were receiving standard of care prophylaxis. There was also an 84% decrease in annualized Factor VIII usage and a 94% decrease in mean FVIII usage annualized between week 5 and 26. In May 2018, BioMarin reported a 98% drop in mean Factor VIII usage the change from 98% to 94% suggests there may be a diminishing treatment effect.
Dec 18 · Two phase III studies (GENEr8-1 and GENEr8-2) ongoing, both with estimated primary completion date of Dec 2022. 
Dec 17 · Press reports claim this could be a cure for haemophilia, following results published in NEJM. A single infusion of the gene therapy drug showed improved levels of the essential blood clotting protein Factor VIII, with 85% of patients achieving normal or near-normal Factor VIII levels even many months after treatment. The transformational results have particular significance as the first successful gene therapy trial for haemophilia A .
Dec 17 · Results of PI/II study (NCT02576795) published in NEJM. A single intravenous dose of AAV5-hFVIII-SQ was infused in 9 men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected .
Oct 16 · MHRA, based on a review of data from nine enrolled subjects, approves continuation of enrolment in a PI/II study, designed to assess the safety and efficacy of BMN 270 in patients with severe haemophilia A; recruitment is expected to resume before end of 2016 (NCT02576795). The MHRA also approved increasing the additional enrolment to up to six patients, of whom three will be enrolled at the 4 x 1013 vg/kg dose and an additional three at the same dose or a previously tested 6 x 1013 vg/kg dose, as well as approved the removal of the requirement for prophylactic corticosteroid therapy for the additional subjects; threshold to initiate therapeutic corticosteroids has also been increased. Data from these subjects will support the design of the planned PIIb study. BioMarin, in June 2016, had suspended enrolment in the trial due to reports of elevated alanine aminotransferase (ALT) levels in some patients. Based on the results, prophylactic corticosteroid therapy was started and no abnormal levels of ALT were observed after that .