The Lancet Respiratory Medicine: Clinical trial finds inhaled immune response protein increases odds of recovery for hospitalised COVID-19 patients
Peer-reviewed / Randomised Controlled Trial / People
- Inhaled delivery of a formulation of a key protein involved in the immune response – interferon beta-1a – to hospitalised COVID-19 patients in the UK reduced the odds that they would develop severe disease or die from SARS CoV-2 infection.
- Those patients who received inhaled interferon beta-1a were more than twice as likely to recover from COVID-19 infection to a point where everyday activities were not limited compared with those who received a placebo.
- The trial included 101 patients, with the data providing strong rationale for larger studies to further investigate the impact of this treatment on clinical outcomes.
Hospitalised COVID-19 patients in the UK who received an inhaled form of interferon beta-1a (SNG001) were more likely to recover and less likely to develop severe symptoms than patients who received a placebo, according to a new clinical trial published in The Lancet Respiratory Medicine journal. This is the first evidence published in a peer-reviewed medical journal that inhaled interferon beta-1a could lessen the clinical consequences of COVID-19 and serves as proof-of-concept that this treatment could help hospitalised patients recover, but further research is required.
As the number of COVID-19 infections continues to rise around the world, there is a pressing need to develop new treatments for the more severe and life-threatening symptoms such as pneumonia and respiratory failure.
Interferon beta is a naturally occurring protein that coordinates the body’s immune response to viral infections. Laboratory studies have found that the SARS CoV-2 virus directly suppresses the release of interferon beta, while clinical trials demonstrate decreased activity of this important protein in COVID-19 patients. The formulation of interferon beta used in this new study – SNG001 – is directly delivered to the lungs via inhalation and has been trialled in the treatment of asthma and chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the safety and efficacy of SNG001 to treat hospitalised COVID-19 patients.
The trial was conducted at nine UK hospitals with patients who had a confirmed SARS-CoV-2 infection. It compared the effects of SNG001 and placebo given to patients once daily for up to 14 days, and followed up patients for a maximum of 28 days after starting the treatment. Patients were recruited from March 30 to May 30, 2020, and were randomly assigned to receive the treatment or a placebo. All members of the research team were blinded to which group the patients were allocated. During the study, changes in the clinical condition of patients were monitored.
Of the 101 patients enrolled in the study, 98 patients were given the treatment in the trial (three patients withdrew from the trial) – 48 received SNG001 and 50 received a placebo. At the outset of the trial 66 (67%) patients required oxygen supplementation at baseline (29 people in the placebo group and 37 in the SNG001 group). Patients who received SNG001 were twice as likely to show an improvement in their clinical condition at day 15 or 16, compared with
Rhythm Pharmaceuticals Announces Publication of Results from Phase 3 Clinical Trials of Setmelanotide in The Lancet Diabetes & Endocrinology
Largest studies in POMC and LEPR deficiency obesities demonstrate that treatment with setmelanotide reduced body weight and hunger
BOSTON, Oct. 30, 2020 (GLOBE NEWSWIRE) — Rhythm Pharmaceuticals, Inc. (Nasdaq:RYTM), a late-stage biopharmaceutical company aimed at developing and commercializing therapies for the treatment of rare genetic disorders of obesity, announced today that results from two pivotal Phase 3 studies evaluating setmelanotide in proopiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity were published in The Lancet Diabetes & Endocrinology. As previously reported, data from the studies demonstrate that treatment with setmelanotide, the company’s melanocortin-4 receptor (MC4R) agonist, led to statistically significant and clinically meaningful reductions of weight and hunger.
“Results from Rhythm’s pivotal Phase 3 studies, which are the largest studies to date in POMC and LEPR deficiency obesities, provide evidence regarding the safety and efficacy of setmelanotide and we believe they validate its potential long-term use as a novel treatment for severe obesity and hyperphagia,” said co-author Peter Kühnen, M.D., Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Germany. “It is important to recognize the signs of these rare genetic disorders because we may soon have a targeted treatment option available for the first time for obesity disorders caused by impairments of the MC4R pathway.”
Rhythm initially reported positive topline data from the Phase 3 studies in August 2019 and subsequently presented updated data in a late-breaking research forum during the 37th Annual Meeting of The Obesity Society at ObesityWeek® 2019.
Eight of 10 participants with POMC deficiency obesity (80%; P<0.0001 compared with historical data) and five of 11 participants with LEPR deficiency obesity (45%; P=0.0001 compared with historical data) achieved at least 10 percent weight loss at approximately one year. The mean percent change in “most hunger” score in participants aged 12 years and older was -27.1 percent (n=7; P=0.0005) in POMC deficiency obesity and -43.7 percent (n=7; P<0.0001) in LEPR deficiency obesity. Consistent with prior clinical experience, setmelanotide was generally well-tolerated in both trials. The most common adverse events were injection site reaction, skin hyperpigmentation, and nausea.
“These results are significant because, as we know from natural history data, individuals living with POMC or LEPR deficiency obesity consistently experience substantial weight gain each year beginning in early childhood, and we would not expect any of these patients to be able to achieve 10 percent weight loss over the course of a year without continued treatment,” said co-author Karine Clément, professor of nutrition at Pitié-Salpêtrière hospital and Sorbonne University in Paris. “These data and the significant unmet need to address the obesity and hyperphagia caused by rare genetic disorders of obesity underscore the importance of testing for genetic variants that may impair MC4R activation and lead to severe obesity.”
In May 2020, Rhythm announced that the U.S. Food and Drug Administration (FDA) accepted the company’s New Drug Application (NDA) for setmelanotide for the treatment of POMC deficiency obesity and LEPR deficiency obesity, granted Priority Review of the NDA and assigned a Prescription Drug