NICE Backs Donidalorsen for Hereditary Angioedema and Acalabrutinib for Blood Cancers

The National Institute for Health and Care Excellence has supported several new treatment pathways covering hereditary angioedema, mantle cell lymphoma, and chronic lymphocytic leukaemia.

The recommendations could expand access to donidalorsen for eligible patients with recurrent hereditary angioedema and introduce two acalabrutinib-based treatment approaches for adults with previously untreated blood cancers.

Donidalorsen Recommended for Hereditary Angioedema

NICE has recommended donidalorsen as a preventive treatment for people aged 12 years and older with hereditary angioedema who experience at least two attacks each month.

Hereditary angioedema is a rare genetic condition that can cause sudden and potentially serious swelling in areas such as the skin, gastrointestinal tract, and airways. Preventive treatment is intended to reduce the frequency of attacks rather than manage an episode after it has already started.

Current preventive options include berotralstat, C1 esterase inhibitors, garadacimab, and lanadelumab.

Clinical trial evidence showed that donidalorsen reduced the frequency of attacks compared with placebo. However, the medicine has not been directly compared with the other established preventive therapies.

NICE’s indirect comparisons were considered uncertain, but suggested that donidalorsen is likely to provide similar clinical benefit to berotralstat, C1 esterase inhibitors, four-weekly lanadelumab, and garadacimab.

The economic assessment found donidalorsen to be a cost-effective option when compared with berotralstat, C1 esterase inhibitors, and lanadelumab. Garadacimab was considered the most relevant comparator, and the analysis indicated similar health-related quality of life with comparable or lower lifetime treatment costs for donidalorsen.

Patients who began donidalorsen through the NHS before the latest guidance may continue under their existing arrangements until they and their healthcare professional decide that stopping treatment is appropriate. For younger patients, the decision should involve the patient, their clinician, and their parents or carers.

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Acalabrutinib Combination Approved for Untreated Mantle Cell Lymphoma

NICE has recommended acalabrutinib with bendamustine and rituximab for adults with untreated mantle cell lymphoma who are not suitable candidates for an autologous stem cell transplant.

The recommendation applies within the medicine’s marketing authorization and is subject to the commercial agreement supplied by the manufacturer.

For this patient group, bendamustine combined with rituximab is commonly used as the existing treatment approach.

Evidence from clinical trials showed that adding acalabrutinib prolonged the period before the lymphoma worsened compared with bendamustine and rituximab alone. In the evidence reviewed by NICE, median progression-free survival reached 72.5 months with the acalabrutinib combination, compared with 47.8 months for standard therapy.

The economic analysis placed the combination within the range NICE considers an appropriate use of NHS resources. The recommendation could benefit approximately 350 adults with previously untreated mantle cell lymphoma who cannot receive an autologous transplant.

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NICE has also recommended acalabrutinib combined with venetoclax as an option for adults with previously untreated chronic lymphocytic leukaemia.

NICE has also recommended acalabrutinib combined with venetoclax as an option for adults with previously untreated chronic lymphocytic leukaemia.

The recommendation covers the combination without obinutuzumab. The evaluation did not include the three-drug regimen because the manufacturer did not submit evidence for acalabrutinib, venetoclax, and obinutuzumab in its economic analysis.

Existing treatment options for untreated chronic lymphocytic leukaemia include:

• Venetoclax with ibrutinib.

• Venetoclax with obinutuzumab.

• Acalabrutinib alone.

• Zanubrutinib alone.

  
  

Acalabrutinib and venetoclax have not been tested directly against all of these standard options in a head-to-head clinical trial. NICE instead considered indirect comparisons with venetoclax plus ibrutinib, venetoclax plus obinutuzumab, and ibrutinib monotherapy.

Because ibrutinib and acalabrutinib work through the same broad treatment pathway, the available evidence suggested comparable clinical effectiveness. NICE acknowledged uncertainty around the indirect comparisons but concluded that acalabrutinib plus venetoclax was likely to provide similar clinical benefit to the established alternatives.

The most likely cost-effectiveness estimates fell within the range NICE considers acceptable for NHS use. Patients who had already started the combination before publication of the guidance may continue treatment under their existing funding arrangements until they and their NHS clinician decide that discontinuation is appropriate.