A one-off gene therapy infusion costing more than $5 million that is purported to be the world most expensive medicine has received provisional approval from the TGA  for use in Australians with haemophilia B.

Etranacogene dezaparvovec (Hemgenix), marketed by CSL Behring, is a single-infusion gene therapy designed to introduce a copy of the Factor IX (FIX) gene to address the lack of functional FIX protein expression in a haemophilia B patient.

The medicine was listed on the Australian Register of Therapeutic Goods (ARTG) on 19 March by the TGA, following its previous granting of Orphan drug status.

The listed indication is for treatment of adults with haemophilia B (congenital factor IX deficiency), without a history of factor IX inhibitors, who:,- currently use factor IX prophylaxis therapy, or,- have current or historical life-threatening haemorrhage, or repeated, serious spontaneous bleeding episodes.

Hemgenix has been available in the US since 2022, where it is priced at US$3.5 million (AU$5.3 million).

The company says the costs of the drug reflects its “groundbreaking” status as a single, durable therapy for haemophilia B compared to the current regime of regular prophylactic infusions of Factor IX, which temporarily replace low levels of the clotting factor.

The question of whether Hemgenix receives public funding for Australians with haemophilia B now depends on an application (link) to the Medicare Services Advisory Committee (MSAC) made on behalf of the National Blood Authority.

The application is due to be considered at MSAC’s August meeting. According to the proposal, evidence to support the use of Hemgenix comes from the phase 3 HOPE-B trial, whose two year results were recently published in The Lancet Haematology (link here).

The latest analysis of the study involving 54 adults males with haemophilia B showed that in the seven -24 months after infusion the mean adjusted ABR significantly reduced from 4·18 to 1·51 (p=0·0002) for all bleeds and from 3·65 to 0·99 (p=0·0001) for factor IX-treated bleeds.

During each six-month period after gene therapy at least 67% of participants experienced no bleeding (36 of 54 during months 0–6 and stable thereafter), compared with 14 (26%) of 54 during the study lead-in period.

At 24 months after gene therapy, one participant had one-stage factor IX activity less than 5%, whereas 18 (33%) had factor IX activity more than 40% (non-haemophilia range), with mean factor IX activity stable and sustained at 36·7% (SD 19·0%).

Also, 96% (52  of 54) of participants expressed endogenous factor IX, remaining free of factor IX prophylaxis at month.

The study authors noted that durability and sustainability of factor IX activity levels were reported in patient subgroups of special interest, such as patients with or without detectable AAV5 neutralising antibody titres of 678 or less before treatment, and patients who experienced liver inflammation after gene therapy.

The results also showed that the factor IX range patients are in directly relates to the probability of becoming bleed-free and avoiding factor IX infusions, they said.

“For patients, the data provide reassurance that etranacogene dezaparvovec can provide meaningful and stable correction of haemophilia B for at least two years,” they concluded.

An accompanying commentary said the two-year results were encouraging and another investigational gene therapy for haemophilia B, scAAV2/8-LP1-hFIXco, “has demonstrated stable factor IX expression for more than 10 years, suggesting at least the potential of very long- term benefit of this therapeutic approach.”