In November 2019, BioMarin, a biotechnology company specialising in developing therapies for rare diseases driven by genetic causes, submitted a marketing authorization application (MAA) to the European Medicines Association (EMA) for its investigational product valoctocogene roxaparvovec, a gene therapy targeted to patients with severe haemophilia A. The EMA validated the application in December 2019 and regulatory review is expected to start this month. If approved, BioMarin’s candidate will be the first gene therapy product to ever become marketed in the entire haemophilia market, including both haemophilia A and B.

Haemophilia A and B are congenital, genetic X-linked deficiencies in the blood clotting factor VIII (FVIII) and clotting factor IX (FIX), respectively. These two clotting factors have different half-life durations in the blood. While people with severe haemophilia A generally need prophylaxis (preventative) injections three times a week, people with severe haemophilia B need them twice a week. GlobalData’s primary research revealed that patients with severe forms of the disease are increasingly treated on a prophylactic basis rather than on-demand after bleeds, since this significantly reduces the occurrence of bleeding episodes. The frequent prophylactic infusions of recombinant FVIII (rFVIII) or recombinant FIX (rFIX) begin from the first one or two years of life, often continuing throughout adulthood. Gene therapies are anticipated to address the significant unmet need for therapies that can reduce the number of weekly prophylactic infusions and alleviate some of this treatment burden. US key opinion leaders (KOLs) interviewed by GlobalData find the greatest unmet need in haemophilia to be the need for a cure, and in their opinion gene therapy could potentially offer a cure in the future.

BioMarin’s recent submissions of an MAA in November 2019 to the EMA and of a biologics license application (BLA) in December 2019 to the FDA were based on results from a Phase I/II study (BioMarin Pharmaceutical, NCT02576795) alongside interim analysis results from the ongoing Phase III GENEr8-1 study (BioMarin Pharmaceutical, NCT03370913). The estimated primary completion date for the GENEr8-1 trial is December 2022. The three-year follow-up of the Phase I/II clinical trial showed positive results, with the median number of annualized treated bleeding events at zero and a reduction of the median use of exogenous factor VIII from 138.5 infusions to 0 infusions per year, in 7 out of 15 participants. These results were published in the New England Journal of Medicine in January 2020. Valoctocogene roxaparvovec has received breakthrough designation from the FDA and accelerated assessment status from the EMA. Additionally, the gene therapy has received Orphan Drug Designation from both regulatory authorities.

Given the great potential of gene therapy in the haemophilia market, more companies are developing gene therapies for both indications, A and B. Spark Therapeutics, Pfizer, and UniQure all have gene therapy products in Phase III development. Pfizer and UniQure are testing their drugs, fidanacogene elaparvovec and AMT-061 respectively, in haemophilia B, while Spark is chasing after BioMarin in haemophilia A with its pipeline therapy SPK-8011.

The haemophilia market was valued at $4.3 billion in the US and $2 billion in the 5EU (France, Germany, Italy, Spain, UK) in 2018. According to GlobalData’s ten-year forecast, haemophilia total sales are expected to reach $5.1 billion in the US by 2028 with a compound annual growth rate (CAGR) of 1.6%, and $3.3 billion in the 5EU with a CAGR of 5.3%. Gene therapies are expected to capture 7.5% of the market in the US and 18.6% of the market in the 5EU by 2028.

US KOLs interviewed by GlobalData consider the time to market a deciding factor for the success of a product and agree that a first-in-market drug can achieve higher market shares than its contenders. Following the MAA submission to the EMA on November 21, 2019, BioMarin’s stock price grew an impressive 12.13% over the past two months. The approval of valoctocogene roxaparvovec will greatly contribute to BioMarin’s profits and further growth.