AstraZeneca's Long-Acting C5 Inhibitor Ultomiris Receives EU Approval for Pediatric and Adolescent PNH Patients

AstraZeneca recently announced that the European Commission (EC) has approved an expanded indication for the long-acting C5 inhibitor Ultomiris (ravulizumab) for the treatment of pediatric (weighing ≥10 kg) and adolescent patients with paroxysmal nocturnal hemoglobinuria (PNH). Specifically, the approval covers pediatric and adolescent PNH patients experiencing bleeding or exhibiting clinical symptoms indicative of high disease activity, as well as pediatric and adolescent PNH patients who are clinically stable after at least six months of treatment with Soliris (eculizumab).

In the European Union, Ultomiris was approved in July 2019 for the treatment of adult patients with PNH. Ultomiris is a long-acting C5 complement inhibitor that inhibits the C5 protein in the complement cascade of the human immune system, providing immediate, complete, and sustained complement inhibition.

With this latest approval, Ultomiris has become the first and only medicine approved in the European Union for children and adolescents with PNH. Results from the Phase 3 clinical trial demonstrate that Ultomiris reduces the treatment burden for pediatric PNH patients and their families, with its efficacy and safety confirmed.

In June 2021, the U.S. FDA approved an expanded indication for Ultomiris for the treatment of pediatric (1 month of age and older) and adolescent patients with PNH. Ultomiris is the first and only treatment for PNH patients in this age group in the United States.

PNH is a blood disorder characterized by complement-mediated red blood cell destruction, which can cause a wide range of debilitating symptoms and complications, including systemic thrombosis that may lead to organ damage and premature death. The symptoms and complications of PNH result from a lack of regulation or control of the complement system, which is a critical component of the human immune system.

Since its initial approval in 2018, Ultomiris has rapidly become the standard of care for adult patients with PNH. Ultomiris functions by inhibiting the C5 protein in the terminal complement cascade, while preserving the remaining immune system's ability to combat common pathogens and infections. By providing immediate, complete, and sustained terminal complement inhibition, Ultomiris reduces the risk of intravascular red blood cell destruction (intravascular hemolysis and thrombosis).

This EU approval is based on the results of a Phase 3 clinical study. The data demonstrated that in pediatric and adolescent patients under 18 years of age, Ultomiris effectively achieved complete C5 complement inhibition over a 26-week treatment period. Furthermore, no treatment-related serious adverse events were reported with Ultomiris, and no patients discontinued treatment or experienced breakthrough hemolysis during the initial evaluation period; the latter could lead to disabling or potentially life-threatening blood clots.

The efficacy and safety of Ultomiris in pediatric and adolescent patients with PNH are consistent with the established profile of Ultomiris in clinical studies of adult patients with PNH, representing a broad PNH patient population in real-world clinical settings.

In December 2020, AstraZeneca announced the acquisition of rare disease leader Alexion for $39 billion in cash and stock. The transaction was officially completed in July 2021. The successful completion of this acquisition marks AstraZeneca's entry into the rare disease therapeutics sector, ushering in a new chapter for the company. Leveraging Alexion's innovative complement biology platform and robust pipeline, AstraZeneca has strengthened its scientific leadership in immunology and will continue to advance the discovery and development of therapies for patients with rare diseases. Rare diseases represent a high-growth, rapidly innovating therapeutic area with significant unmet medical needs, positioning them as a key growth opportunity for AstraZeneca.

Alexion’s flagship products are two C5 complement inhibitors, Soliris and Ultomiris, with the latter being a long-acting version of the former. Both drugs exert their therapeutic effects by inhibiting the C5 protein at the terminal stage of the complement cascade. The complement cascade is a component of the immune system, and its uncontrolled activation plays a pivotal role in a variety of severe rare and ultra-rare diseases.

Soliris was first approved for marketing in 2007 and is currently approved for multiple ultra-rare diseases, including: Paroxysmal Nocturnal Hemoglobinuria (PNH), atypical Hemolytic Uremic Syndrome (aHUS), generalized Myasthenia Gravis (gMG), and Neuromyelitis Optica Spectrum Disorder (NMOSD). Ultomiris, an upgraded version of Soliris, is a second-generation, long-acting C5 complement inhibitor. It was first approved for marketing in late 2018, with approved indications including PNH and aHUS.

Soliris is one of the best-selling rare disease drugs globally, with sales reaching $4.065 billion in 2020. Ultomiris generated sales of $1.077 billion in 2020. The combined sales of these two C5 inhibitors totaled $5.142 billion.

Note: The original text has been abridged.

Source: Ultomiris approved in the EU for children and adolescents with paroxysmal nocturnal haemoglobinuria

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