Regeneron Pharmaceuticals, Inc., a fully integrated biopharma company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion for the marketing authorization in the EU of rilonacept, an interleukin-1 blocker, for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) with severe symptoms, including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children aged 12-year and older.
The positive opinion recommends the granting of a marketing authorization for rilonacept under exceptional circumstances. Such authorizations are permissible for products for which a company can demonstrate that comprehensive data cannot be provided, for example because of the rarity of the condition. Each year, Regeneron will need to provide the EMEA with any new information that may become available for review.
"We are very pleased to receive the EMEA's positive opinion for rilonacept," said Leonard S. Schleifer, president and CEO of Regeneron. "We recognize that rilonacept may help address a significant unmet medical need that exists among CAPS patients in the EU and are therefore committed to helping these patients obtain access to this new treatment."
CAPS are a group of rare, inherited, auto-inflammatory conditions characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain, and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli.
Rilonacept is a targeted inhibitor of interleukin-1 (IL-1), the key driver of inflammation in CAPS. In the pivotal clinical development program, patients treated with rilonacept reported a greater improvement in overall symptom scores than patients treated with placebo. These improvements were sustained over time with continued rilonacept treatment. Patient-reported symptoms assessment, using a validated daily diary instrument, represents a critical measure of effectiveness in a disease characterized by frequent, unpredictable symptom flares of variable severity and duration. Unlike other agents used in the treatment of CAPS, rilonacept is supported by patient-reported symptoms data using a validated assessment instrument.
Rilonacept has been developed as a once-weekly injection which can be administered at home by the patient or their care giver following appropriate training. The most commonly reported adverse reactions with rilonacept were injection-site reaction and upper respiratory tract infection. IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking rilonacept. Treatment should not be initiated in patients with active or chronic infections. Rilonacept should be discontinued if a patient develops a serious infection.
Recently, medical researchers have identified and described a group of rare, inherited, auto-inflammatory disorders, known as Cryopyrin-Associated Periodic Syndromes or CAPS. Three related conditions make up the broader disease known as CAPS: Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). Rilonacept has not been studied in patients with NOMID.
CAPS are characterized by life-long, recurrent symptoms of rash, fever/chills, joint pain, eye redness/pain, and fatigue. Intermittent, disruptive exacerbations or flares can be triggered at any time by exposure to cooling temperatures, stress, exercise, or other unknown stimuli.
CAPS are generally caused by autosomal-dominant mutations (changes) in the NLRP-3 (previously known as CIAS1) gene and resultant alterations in the protein, cryopyrin, which it encodes. Cryopyrin, active in circulating, infection-fighting, white blood cells, controls the production of a protein called interleukin-1 (IL-1). As part of the body's infection-fighting defense system, IL-1 circulates throughout the body and can trigger inflammatory reactions when it binds to inflammatory cells. Researchers have found that alterations in the cryopyrin protein lead to over-production of IL-1, resulting in an inflammatory response and the symptoms of CAPS. Most, but not all, patients with CAPS have the NLRP-3 gene mutation.
The incidence of CAPS has been estimated to be approximately 1 in 1,000,000 people in the EU.
Rilonacept is a targeted inhibitor of interleukin-1 (IL-1), the key driver of inflammation in Cryopyrin-Associated Periodic Syndromes (CAPS). In the pivotal clinical development program for rilonacept, change in disease activity was measured using a composite patient-reported symptom score composed of a daily evaluation of rash, feelings of fever/chills, joint pain, eye redness/pain, and fatigue. Patients treated with rilonacept experienced an improvement in overall symptom scores as compared with patients treated with placebo. These improvements were sustained over time with continued treatment with rilonacept. The most commonly reported adverse reactions with rilonacept were injection-site reaction and upper respiratory tract infection.
In the US, rilonacept (Arcalyst) is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. ARCALYST was approved by the U.S. Food and Drug Administration in February 2008 and has been available in the United States since March 2008.
IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking Arcalyst. Arcalyst should be discontinued if a patient develops a serious infection. Treatment with Arcalyst should not be initiated in patients with active or chronic infections. Taking Arcalyst with tumour necrosis factor inhibitors is not recommended because this may increase the risk of serious infections. Patients should not receive a live vaccine while taking Arcalyst. It is recommended that patients receive all recommended vaccinations prior to initiation of treatment with Arcalyst. Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted. Hypersensitivity reactions associated with Arcalyst (rilonacept) administration have been rare.