The MIROCALS trial, conducted in 220 patients from 17 clinics across the UK and France, in collaboration with eight leading research groups in the UK, France, Italy and Sweden, investigated whether low dose IL-2 can modify aspects of neuro- inflammation, which is believed to play a central role in ALS disease progression. Dr. Gilbert Bensimon presented the top-line results at the International Symposium on ALS / Motor Neuron Diseases. The unadjusted analysis of the primary endpoint showed a 19% reduction in risk of death in IL2 treated patients compared with placebo, which was not statistically significant. However, analysis adjusting for a pre-specified primary core biomarker, cerebrospinal fluid phosphorylated neurofilament heavy chain (CSF-pNFH), demonstrated a statistically significant decrease (73%) in the risk of death for the IL2 group over the 21-month trial period. Interaction by CSF-pNFH levels was found to be selective. The interaction on survival was not present in patients with high CSF-pNFH (21% of study participants), which corresponded with aggressive, fast progressing disease. However, patients with low to moderate CSF-pNFH levels (79% of study participants), correlating with less aggressive disease progression, demonstrated a significant decrease in the risk of death (43%) for the IL2 group. Similarly, a slowing of decline in ALSFRS-R (ALS Functional Rating Scale – Revised, a key metric in functional capability in patients with ALS) was found in the IL2 group of patients with low CSF-pNFH levels (c. 70% of study participants). The treatment was well tolerated, with adverse events recorded as mostly mild to moderate, occurring across both active treatment and placebo arms.
David Bryant, Chief Executive Officer of Clinigen, said: “The MIROCALS Phase II clinical trial data presented is positive news for patients with ALS, for which there is currently no effective treatment, and we look forward to understanding what further research is planned.” Clinigen Limited+44 (0)7957 984570Michelle Shearly, Director of Communicationsmichelle.shearly@clinigengroup.comConsilium Strategic Communications
Mary-Jane Elliott / Matthew Cole / Jessica Hodgson
Tel: +44 (0) 20 3709 5700 Clinigen@consilium-comms.com
Clinigen is a global, specialist pharmaceutical services company focused on providing ethical access to medicines. Its mission is to deliver the right medicine to the right patient at the right time. The Group operates from sites in North America, Europe, Africa and the Asia Pacific. Clinigen has more than 1,000 employees across five continents in 15 countries, with supply and distribution hubs and operational centres of excellence in key long-term growth regions. The Group works with 32 of the top 50 pharmaceutical companies providing access across more than 120 countries. Clinigen acquired the global rights to Proleukin outside the United States in 2018 and the US rights in 2019.
For more information on Clinigen, please visit http://www.clinigengroup.com
Proleukin (Aldesleukin is a recombinant interleukin-2 (IL-2), a cytokine whose role in the immune system has been extensively studied. At conventional doses it is used in the treatment of kidney cancer that has spread to another part of the body (metastatic kidney cancer). It is also currently being studied as part of adoptive cellular therapy. At significantly lower doses than those used in oncology aldesleukin has demonstrated immunomodulatory effects in certain auto-immune and inflammatory disease states by boosting the levels of a particular subset of white blood cells called T-regulatory lymphocytes (Tregs). The Following Information is Intended for the U.S. Audience Only.
Summary of Important Safety Information for Proleukin® (aldesleukin) for injection, for intravenous infusion. Therapy with Proleukin® (aldesleukin) should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress testing and formal pulmonary function testing. Extreme caution should be used in patients with a normal thallium stress test and a normal pulmonary function test who have a history of cardiac or pulmonary disease. Proleukin should be administered in a hospital setting under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. Careful patient selection is mandatory prior to the administration of Proleukin. Evaluation of clinical studies to date reveals that patients with more favorable ECOG performance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with a higher response rate and lower toxicity. Therefore, selection of patients for treatment should include assessment of performance status. Experience in patients with ECOG PS > 1 is extremely limited.
Proleukin is contraindicated in patients with an abnormal thallium stress test or abnormal pulmonary function tests and those with organ allografts. Retreatment with Proleukin is contraindicated in patients who have experienced the following drug-related toxicities while receiving an earlier course of therapy: sustained ventricular tachycardia (≥ 5 beats), cardiac arrhythmias not controlled or unresponsive to management, chest pain with ECG changes, consistent with angina or myocardial infarction, cardiac tamponade, intubation for > 72 hours, renal failure requiring dialysis > 72 hours, coma or toxic psychosis lasting > 48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, GI bleeding requiring surgery. Because of the severe adverse events which generally accompany Proleukin therapy at the recommended dosages, a thorough clinical evaluation should be performed to identify patients with significant heart, lung, kidney, liver or central nervous system impairment in whom Proleukin is not indicated for use. Patients with normal heart, lung, liver and central nervous system function may experience serious, life-threatening or fatal adverse events. Should adverse events, requiring dose modification occur, dosage should be withheld rather than reduced.
Patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy. Capillary leak syndrome (CLS) begins immediately after Proleukin® (aldesleukin) treatment starts and is marked by increased capillary permeability to protein and fluids and reduced vascular tone. Proleukin® (aldesleukin) treatment should be withheld for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, a fall in the systolic blood pressure below 90 mm Hg or onset of cardiac arrhythmias. Recovery from CLS begins soon after cessation of Proleukin therapy. Usually, within a few hours, the blood pressure rises, organ perfusion is restored and reabsorption of extravasated fluid and protein begins. Kidney and liver function are impaired during Proleukin treatment. Use of concomitant nephrotoxic or hepatotoxic medications may further increase toxicity to the kidney or liver. Proleukin enhancement of cellular immune function may increase the risk of allograft rejection in transplant patients. Serious manifestations of eosinophilia involving eosinophilic infiltration of cardiac and pulmonary tissues can occur following Proleukin. Adverse events are frequent, often serious, and sometimes fatal. The following adverse events (Grades 1-4) were seen in ≥ 30% of 525 patients (255 with metastatic kidney cancer and 270 with metastatic melanoma) treated with Proleukin: low blood pressure (71%), diarrhea (67%), low urine output (63%), chills (52%), vomiting (50%), shortness of breath (43%), rash (42%), increased bilirubin in blood (40%), decreased clotting of blood (37%), nausea (35%), confusion (34%), and decreased kidney function (33%). Please see the full Prescribing Information, including Boxed Warning, for Proleukin® (aldesleukin) for injection, for intravenous infusion. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
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