An expensive new haemophilia gene therapy hits the US

The approval is good for CSL, and better for Uniqure.

Move over Skysona: the world has a new most expensive drug. Uniqure and CSL’s haemophilia B gene therapy etranacogene dezaparvovec was yesterday approved in the US as Hemgenix, and priced at $3.5m – above ICER’s recommendation of $3m. 

The FDA granted a generous label, with an indication covering all adult haemophilia B patients. The product also escaped a boxed warning for carcinogenicity, though patients with risk factors for hepatocellular carcinoma must be monitored following its administration.

That said, even a broad label and a high price do not guarantee commercial success, and some gene therapies, including Uniqure’s own Glybera, have floundered post-launch. That is CSL’s problem, since the Australian company has sole responsibility for selling Hemgenix; its inventor Uniqure can sit back and rake in the cash. Uniqure will get up to $1.5bn in commercial milestones, including $175m upon first US or European sale. 

Royalties, with percentages in the mid-teens to low 20s, are also due. By 2028 royalty payments could top $200m, according to Evaluate Pharma’s consensus. 

Hemgenix will need to see serious uptake, which will in turn necessitate reimbursement, for Uniqure to realise some of the more generous terms of this deal. The small biotech has an enterprise value of around $775m, its shares having risen 7% on news of this approval. 

Hemgenixpensive: the US's costliest gene therapies
Project Company Indication US approval date Price ($m)
Hemgenix Uniqure/CSL Haemophilia B Nov 22, 2022 3.5
Skysona Bluebird Bio Cerebral adrenoleukodystrophy Sep 16, 2022 3.0
Zynteglo Bluebird Bio Beta thalassaemia Aug 17, 2022 2.8
Zolgensma Novartis Spinal muscular atrophy May 24, 2019 2.1
Luxturna Novartis/Roche Biallelic RPE65 mutation-associated retinal dystrophy Dec 19, 2017 0.4*
*Per eye. Source: company communications. 

And the rest

Separately, the approval has implications for Biomarin, among others. That group’s haemophilia A gene therapy, Roctavian, will get an approval decision in the coming quarter. Unlike Hemgenix, it had been expected to face an FDA adcom, but today Biomarin said that this was no longer a requirement. 

Several other groups are following behind, in both major subtypes of haemophilia. Pfizer’s fidanacogene elaparvovec has a phase 3 readout coming early next year in haemophilia B. The Benegene-2 trial has enrolled 45 patients and has annualised bleeding rate as its primary endpoint. 

Pfizer has another phase 3-stage gene therapy, this time for haemophilia A. Giroctocogene fitelparvovec (SB-525) was licensed from Sangamo, and its Affine study recently restarted, having been on clinical hold for over a year after some patients experienced very high factor VIII levels. 

Pivotal data from Affine are expected in 2024, and phase 2 data on a handful of other gene therapies are also due in a similar time frame. But haemophilia B looks like a two-horse race, and Uniqure and CSL are in the lead. 

Selected haemophilia gene therapy projects
Project Company Subtype Status
(etranacogene dezaparvovec)
Uniqure/CSL B Approved Nov 22, 2022
(valoctocogene roxaparvovec)
Biomarin A Filed; Pdufa date Mar 31, 2023, 3yr data from Ph3 GENEr8-1 expected early 2023
Fidanacogene elaparvovec Pfizer/Roche B Ph3 Benegene-2 trial ongoing; data due Q1 2023
Giroctocogene fitelparvovec (SB-525) Sangamo/
A Ph1/2 Alta trial ongoing; 3yr data due at Ash 2022. Ph3 Affine trial restarted after hold; data due H1 2024  
RG6357/SPK-8011 Roche A Ph1/2 trial ongoing; 5yr data due at Ash 2022
RG6358/SPK-8016 Roche A Ph1/2 trial ongoing; data possible 2023
ASC618 ASC Therapeutics A Ph1/2 trial ongoing; data possible 2024
Source: Evaluate Pharma &

This story has been updated to clarify the milestone payments that Uniqure will receive.

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