Uniqure tries to restore gene therapy calm

Adverse event scares have rocked the gene therapy universe, but Uniqure today tried to restore order. The case of liver cancer that had hit the company’s pivotal Hope-B trial of etranacogene dezaparvovec has apparently been determined to be “highly unlikely” to have been due to this haemophilia B gene therapy. The scare had caused etranacogene to go on clinical hold in December, and Uniqure today said its latest findings had been shared with the US FDA, with a view to discussing the hold in the second quarter. Specifically, Uniqure’s investigation found that vector integration in the patient’s tissue sample was extremely rare and randomly distributed, and that the subject had a precancerous state and genetic mutations characteristic of liver cancer and independent of vector integration. Such observations go to the heart of what had been the worst-case scenario, namely that insertional mutagenesis had occurred. The markets sent Uniqure up 10% this morning, the relief reminiscent of Bluebird, which has tried to allay fears over two blood cancer cases that had caused sickle cell studies of its Lentiglobin to be halted. Nevertheless, the risk is real: since December 2018 sellside forecasts for most gene therapies have plummeted.

How the mighty have fallen: sellside forecasts for selected gene therapies
      2024e sales ($m)  
Project Company Indication Forecast in Dec 2018 Forecast today Forecast change
Lentiglobin Bluebird Bio Beta-thalassaemia & sickle cell disease 1,994 306 -85%
SRP-9001 Sarepta Therapeutics Duchenne muscular dystrophy 1,659 654 -61%
SGT-001 Solid Biosciences Duchenne muscular dystrophy 1,589 35 -98%
Zolgensma Novartis Spinal muscular atrophy 1,420 2,048 44%
Valoctocogene roxaparvovec Biomarin  Haemophilia A 1,210 364 -70%
Etranacogene dezaparvovec Uniqure/CSL Haemophilia B 770 505* -34%
RG6357 Roche (ex Spark) Haemophilia A 458 171 -63%
HMI-102 Homology Medicines Phenylketonuria 362 153 -58%
RG6367 Roche (ex Spark) Choroideremia 353 13 -96%
ABO-102 Abeona Therapeutics Mucopolysaccharidosis III 343 65 -81%
Source: Evaluate Pharma sellside consensus. Note: *based on forecast $96m royalties from CSL, and an assumed blended royalty rate of 19% of net sales.

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