NICE recommends Voydeya® (danicopan) with ravulizumab or eculizumab for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults with residual haemolytic anaemia

Danicopan, a first-in-class, oral, Factor D inhibitor as add-on to ravulizumab or
eculizumab improved haemoglobin levels and reduced anaemia and fatigue²

London, 22 October, 2024 – Alexion, AstraZeneca Rare Disease, has received a positive recommendation for Voydeya® (danicopan), from the National Institute for Health and Care Excellence (NICE), as an add-on to ravulizumab or eculizumab as an option for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults who have residual haemolytic anaemia only if they have clinically significant extravascular haemolysis (EVH) while on

treatment with a complement component 5 inhibitor (C5 inhibitor) and the company provides it according to the commercial arrangement.^1,2

PNH is a rare, chronic, and potentially life-threatening blood disorder. It is characterised by red blood cell destruction within blood vessels (also known as intravascular haemolysis) and white blood cell and platelet activation, which can result in thrombosis (blood clots).

Danicopan is a first-in-class, oral, Factor D inhibitor, developed as an add-on to standard-of-care ravulizumab or eculizumab to address the needs of a small number of eligible patients with PNH who experience residual haemolytic anaemia due to clinically significant EVH while treated with a C5 inhibitor.^2,3 Clinically significant EVH results in continued symptoms of anaemia and may require blood transfusions.

Dr Morag Griffin, Consultant Haematologist, Leeds Teaching Hospitals NHS Trust, said: "Today’s recommendation from NICE is a positive milestone for eligible individuals with PNH who experience the added burden of EVH symptoms such as continued anaemia, while treated with a C5 inhibitor. The ALPHA trial investigated the safety and efficacy of danicopan in patients with PNH and EVH, and demonstrates this is a suitable option to support disease control, and may help to improve patients’ quality of life.”

Deborah Richards, General Manager, Alexion, AstraZeneca Rare Disease said: "Danicopan, a first-in-class, oral, Factor D inhibitor, is the latest innovation in decades of work in our complement inhibition research programme. We’re committed to bettering the lives of all patients with PNH and we look forward to making this treatment available to eligible patients across the country.”

The NICE recommendation is based on the results of the pivotal ALPHA Phase III trial. Results from the 12-week primary evaluation period of the trial were published in The Lancet Haematology.² The ALPHA Phase III trial evaluated the efficacy and safety of danicopan as an add-on to ravulizumab or eculizumab in patients with PNH who experienced clinically significant EVH.² Results showed that danicopan vs placebo met the primary endpoint of change in haemoglobin from baseline to week 12 (LSM change from baseline: danicopan 2.94 g/dL [95% CI 2.52 to 3.36]; placebo, 0.50 g/dL [-0.13 to 1.12]; LSM difference between danicopan and placebo, 2.44 g/dL [95% CI 1.69 to 3.20] p<0.0001).

All key secondary endpoints were met comparing danicopan vs placebo at week 12: haemoglobin increase ≥2g/dL compared to baseline in the absence of transfusion (25 participants (60%) of 42 vs 0 of 21 placebo participants (adjusted difference, 47% [95%CI 29 to 65]; p<0.0001); transfusion avoidance (35 (83%) of 42 danicopan participants vs 8 (38%) 

of 21 placebo participants (adjusted difference, 42% [23 to 61]; p=0.0004)); LSM change from baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) (7·97 (95% CI 5·72 to 10·23) versus 1·85 (–1·31 to 5·02) in danicopan versus placebo groups, respectively (LSMD 6·12 [95% CI 2·33 to 9·91] p=0·0021; and change from baseline to week 12 in ARC (absolute reticulocyte count) (LSM change −83·8 × 10⁹/L (95% CI–101·6 to –65·9) vs 3·5 × 10⁹/L (–21·9 to 28·8). LSMD −87·2 × 10⁹/L (−117·7 to −56·7); p<0·0001.²

Results from the ALPHA Phase III trial showed danicopan was generally well tolerated, and no new safety concerns were identified. The most common adverse reactions are pyrexia, headache, hepatic enzyme increase, and pain in the extremity.⁴

For further information about danicopan, such as the licensed indication and full safety profile, please refer to the summary of product characteristics.⁴

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PNH

PNH is a rare, chronic, and potentially life-threatening blood disorder. It is characterised by red blood cell destruction within blood vessels (also known as intravascular haemolysis) and white blood cell and platelet activation, which can result in thrombosis (blood clots).^5-7

PNH is caused by an acquired genetic mutation that may happen any time after birth and results in the production of abnormal blood cells that are missing important protective blood cell surface proteins. These missing proteins enable the complement system, which is part of the immune system and is essential to the body’s defence against infection, to ‘attack’ and destroy or activate these abnormal blood cells.⁵ Living with PNH can be debilitating, and signs and symptoms may include blood clots, abdominal pain, difficulty swallowing, erectile dysfunction, shortness of breath, excessive fatigue, anaemia and dark-coloured urine.^5,8,9

Clinically Significant EVH

EVH, the removal of red blood cells outside of the blood vessels, can occur in patients with PNH who are treated with C5 inhibitors.^10,11 Since C5 inhibition enables PNH red blood cells to survive and circulate, EVH may occur when these now surviving PNH red blood cells are marked by proteins in the complement system for removal by the spleen and liver.^5,7,12 PNH patients with EVH may continue to experience anaemia, which can have various causes, and may require blood transfusions.^10,11,13,14 A subset of people living with PNH who are treated with a C5 inhibitor experience clinically significant EVH, which results in continued symptoms of anaemia and may require blood transfusions.^5,8,15,16

ALPHA

The ALPHA Phase III trial evaluated the efficacy and safety of danicopan as an add-on to ravulizumab or eculizumab in patients with PNH who experienced clinically significant EVH.² In the double-blind, placebo-controlled, multiple-dose trial, patients were enrolled and randomised to receive danicopan or placebo (2:1) in addition to their ongoing ravulizumab or eculizumab therapy for 12 weeks. A prespecified interim analysis was performed once 63 randomised patients had completed 12 weeks of the primary evaluation period or discontinued treatment as of 28 June 2022. At 12 weeks, patients on placebo plus ravulizumab or eculizumab were switched to danicopan plus ravulizumab or eculizumab, and patients on danicopan plus ravulizumab or eculizumab remained on this treatment for an additional 12 weeks. Patients who completed both treatment periods (24 weeks) had the option to participate in a two-year long-term extension period and continue to receive danicopan in addition to ravulizumab or eculizumab. The open-label period of the study is ongoing.^2,17

^* Results showed that danicopan met the primary endpoint of change in haemoglobin from baseline to week 12 (LSM change from baseline: danicopan 2.94 g/dL [95% CI 2.52 to 3.36]; placebo, 0.50 g/dL [-0.13 to 1.12]; LSM difference between danicopan and placebo, 2.44 g/dL [95% CI 1.69 to 3.20] p<0.0001).²

Voydeya (danicopan)

Voydeya (danicopan) is a first-in-class, oral, Factor D inhibitor. The medication works by selectively inhibiting Factor D, a complement system protein that plays a key role in the amplification of the complement system response. When activated in an uncontrolled manner in PNH, the complement cascade over-responds, leading the body to attack its own healthy cells. Danicopan has been granted Breakthrough Therapy designation by the US Food and Drug Administration and PRIority MEdicines (PRIME) status by the European Medicines Agency. Danicopan has also been granted Orphan Drug Designation in the US, EU and Japan for the treatment of PNH.

Danicopan is licensed in the UK, US, EU and Japan as add-on therapy to ravulizumab or eculizumab for the treatment of eligble adults with PNH.

Alexion is also evaluating danicopan as a potential monotherapy for other indications.

Alexion

Alexion, AstraZeneca Rare Disease is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more people with rare disease around the world. It is headquartered in Boston, US.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.co.uk and follow the Company on social media @AstraZeneca.