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New HTA Decisions in England
October 2021
Drug name
ORLADEYO® (berotralstat)
Decision date
Therapeutic area
Blood and immune system conditions
Therapeutic sub area
Recommended with restrictions
For routine prevention of recurrent attacks of hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older.
Decision Detail
1.1 It is recommended only if: • patients have at least 2 attacks per month, and • it is stopped if the number of attacks per month does not reduce by at least 50% after 3 months. It is only recommended if the company provides berotralstat according to the commercial arrangement (simple discount patient access scheme). 1.2 This recommendation is not intended to affect treatment with berotralstat that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. For young people, this decision should be made jointly by the clinician and the young person and the young person's parents or carers.
The clinical-effectiveness evidence for berotralstat comes from APeX 2 which is a 3-part, phase 3, randomised, double-blind, placebo-controlled trial in people 12 years or older with type 1 or type 2 hereditary angioedema. Results from the intention to treat population of APeX 2 show a statistically significant reduction in mean monthly attack rates of 44% with berotralstat compared with placebo. Similar results were observed for the subgroup of patients from APeX 2 who had 2 or more attacks at baseline. The patient experts explained that a prophylactic treatment that reduces attack rate could potentially be life changing for people with this condition. However, they explained that although the reduction in attack rate is a clinically important outcome for people with hereditary angioedema, the reduction in attack severity would be equally important. They noted that if a treatment did not reduce attack rate, but reduced attack severity, they would still value the option to have that treatment. They further highlighted that the hospitalisation of people with hereditary angioedema is often because of attack severity rather than attack rate. The company and the ERG stated that the location of the attack (such as the limbs or the airway) and duration of attack were used as a proxy for attack severity in the model. The company explained that the direct measure of attack severity in the trial was subjective and did not show that berotralstat reduced attack severity more than placebo. This was despite the proxy measures showing that berotralstat reduced severity. So this subjective measure was not considered credible enough to be included as an outcome in the analysis. The committee recognised that it is important to consider evidence on attack severity as well as attack rate when assessing the clinical effectiveness of berotralstat. The committee was dissatisfied that direct data on severity from APeX 2 was not presented and applied in the model but accepted that there are limitations with this data. It concluded that the clinical evidence suggests berotralstat is more effective than placebo in reducing attack rate, but its effect on attack severity is not known. The committee took into account the updated confidential commercial arrangement for berotralstat and the confidential Commercial Medicines Unit prices for standard care treatments used for acute attacks. It agreed that the most plausible ICER was within the range NICE normally considers to be a cost-effective use of NHS resources, that is £20,000 to £30,000 per QALY gained. The exact figure cannot be reported because of the confidential prices for the treatments used for acute attacks. So, it concluded that berotralstat is recommended for preventing recurrent attacks of hereditary angioedema for people 12 years and older. But it is recommended only if they have at least 2 attacks per month, and it is stopped if the number of attacks per month does not reduce by at least 50% after 3 months.