NICE Set to Approve First Licensed Treatment for Progressive Fibrosing Interstitial Lung Diseases

Dawn O'Shea

October 21, 2021

The National Institute for Health and Care Excellence (NICE) has published new draft guidance which recommends nintedanib (Ofev, Boehringer Ingelheim) as an option for treating chronic progressive fibrosing interstitial lung diseases (PF-ILD). The treatment can be used alongside immunosuppressants.

The decision to recommend the treatment is based on evidence from the phase 3 randomised, multicentre INBUILD trial which compared nintedanib with placebo in people with PF-ILD. A total of 332 participants were randomly assigned to receive nintedanib and 331 received placebo. Twenty-two participants were from the UK.

The trial consisted of two parts. In Part A, participants received nintedanib or placebo for 52 weeks. In part B, participants continued blinded, randomised treatment beyond week 52. The trial continued until all patients reached their week-52 visit or withdrew.

An extension study, INBUILD-ON (n=436, completed), offered open-label nintedanib to participants who investigators deemed would benefit.

INBUILD participants were not permitted to receive immunosuppressants other than ≤20 mg per day of oral corticosteroids at randomisation and for the first six months or unless they underwent a wash-out period four to eight weeks before randomisation. After the first six months and for the rest of the 52-week period, patients with worsening ILD or connective tissue disease could be treated with immunosuppressants. During this time, approximately 16% of patients started immunosuppressants (21% in the placebo arm and 11% in the nintedanib arm).

The trial showed that nintedanib was associated with a slower decline in lung function compared with placebo.

The primary endpoint was annual rate of decline in forced vital capacity (FVC; millilitres per year). Over 52 weeks, the decline in lung function differed between the nintedanib (−80.8 mL/year) and placebo (−187.8 mL/year) arms. Nintedanib was also associated with a slower decline in FVC% predicted from baseline compared with placebo at week 52 (mean difference, 3.2%; 95% CI, 2.09%-4.40%).

Secondary endpoints assessed in INBUILD included overall survival, change from baseline in the score for the King’s Brief Interstitial Lung Disease questionnaire (a health-related quality-of-life measure) and time until first acute exacerbation of ILD or death. Other endpoints included the EQ-5D questionnaire and safety.

The trial was not powered to detect a difference in mortality, however, the HR for death for people randomly assigned to nintedanib (4.8%; 16/332) compared with people randomly assigned to placebo (5.1%; 17/331) at 52 weeks was estimated to be 0.94 (95% CI, 0.47-1.86; P=.85). The appraisal committee noted the wide confidence intervals.

In the INBUILD 52-week period, gastrointestinal discomfort, especially diarrhoea, was the most common adverse event, occurring in 66.9% of participants in the nintedanib arm compared with 23.9% in the placebo arm. Nintedanib was also associated with a higher incidence of serum markers of hepatic injury. Nintedanib was not associated with an increased risk of infection, unlike immunosuppressants.

The price of nintedanib is £2151.10 per pack of 60 capsules, each containing 150 mg. However, the company has agreed to a patient access scheme, which makes the treatment available to the NHS at a discount. The size of the discount is in confidence. The recommended dose is one capsule of 150 mg twice daily approximately 12 hours apart.

It is estimated that around 900 people will be eligible for the treatment in England.

The final draft guidance has been forwarded to those who contributed to the initial consultation process, who will have an opportunity to appeal the decision or highlight any errors. The final guidance is due to be published on 17 November 2021.

This article originally appeared on Univadis, part of the Medscape Professional Network.


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