granulomatous infection lung :: Article CreatorKinevant Sciences Announces Topline Results From Phase 2 RESOLVE-Lung Study Of Namilumab In Chronic Active Pulmonary Sarcoidosis
Namilumab failed to show treatment benefit in patients with pulmonary sarcoidosis Further development of namilumab for the treatment of sarcoidosis will be discontinued BASEL, Switzerland and LONDON and NEW YORK, Dec. 03, 2024 (GLOBE NEWSWIRE) -- Kinevant Sciences, a clinical-stage biopharmaceutical company developing new medicines for rare inflammatory and autoimmune diseases, today announced its Phase 2 study failed to show treatment benefit in patients with chronic active pulmonary sarcoidosis. The Phase 2 RESOLVE-Lung study (NCT05314517) evaluated the efficacy and safety of namilumab, an investigational anti-GM-CSF monoclonal antibody administered once-monthly as a subcutaneous injection, in participants with chronic active pulmonary sarcoidosis.
Primary Endpoint Details: Namilumab failed to meet the primary endpoint of proportion of subjects with a Rescue Event during the double-blind period.
Secondary Endpoints Details: Secondary efficacy endpoints, including change in percent predicted forced vital capacity, corticosteroid tapering success, and change in the patient reported King's Sarcoidosis Questionnaire failed to show a treatment benefit consistent with the primary endpoint.
Safety Details: The safety profile of namilumab in RESOLVE-Lung remains similar to previous studies.
With these results, Kinevant will be discontinuing further development of namilumab for the treatment of sarcoidosis. Kinevant is committed to publishing the results of RESOLVE-Lung to inform future sarcoidosis research.
"Although RESOLVE-Lung failed to show a treatment benefit for namilumab, the significant amount of information produced by the study will be tremendously helpful to those in the field who are committed to improving the lives of sarcoidosis patients," said Bill Gerhart, CEO of Kinevant. "I would like to thank all the patients who courageously volunteered to participate in the study, as well as the Kinevant team, industry partners, principal investigators, site staff, and patient advocacy groups who all worked together to successfully conduct this important study for sarcoidosis."
"Risk-taking in clinical development is at the heart of our industry, and core to Roivant's mission of developing new medicines for patients in need. It's evident from our data that the RESOLVE-Lung study was thoughtfully designed and gave us a clear read on the potential benefits of namilumab in this patient population," said Matt Gline, CEO of Roivant. "Unfortunately science is sometimes humbling, and we are proud to have made the attempt, as well as of our successes in other programs this year. We look forward to taking calculated risks on similar programs in the future."
About RESOLVE-Lung
The RESOLVE-Lung study is a Phase 2 randomized, double-blind, placebo-controlled study of namilumab for the treatment of pulmonary sarcoidosis at sites in the U.S. And Europe. The study enrolled 107 patients with pulmonary sarcoidosis considered to have chronic, active disease not well-controlled despite available therapeutic options. Patients in the study received a once-monthly subcutaneous injection of namilumab or placebo (following the initial dosing period) for approximately six months. All patients who complete the 26-week double-blind treatment period were eligible to participate in a 28-week open-label extension treatment period on namilumab.
The primary endpoint of this study was proportion of subjects with a Rescue Event during the double-blind period. Rescue Event was defined as clinically significant worsening of a subject's sarcoidosis requiring treatment, failure to adhere to the protocol defined OCS taper, or premature discontinuation from the study associated with lack of benefit during the double-blind treatment period.
Study eligibility did not require subjects to be on high dose corticosteroids. If subjects were on >5mg/day of oral corticosteroid (OCS) at baseline, they were required to taper down to 5mg/day 8-10 weeks after randomization. If patients were on an immunosuppressive therapy (IST), they were required to stop the IST at randomization. Notably, all subjects enrolled had evidence of active pulmonary sarcoidosis disease, defined as a positive HRCT scan, significant lung inflammation on PET, and moderate to severe self-reported breathlessness.
About Sarcoidosis
Pulmonary sarcoidosis is a lung disease characterized by the presence of granulomas (clumps of immune cells) of unknown etiology that can cause breathlessness, fatigue, and pain. The resulting inflammation, if not effectively treated, can result in lung tissue scarring (fibrosis), lung dysfunction, and eventually lung failure. Approximately 50% of diagnosed patients require chronic therapy to treat symptoms and prevent progression. Oral steroids (e.G., prednisone) and off-label immunosuppressive therapies (e.G., methotrexate) are first- and second-line therapies respectively for sarcoidosis; however, these therapeutic options are often not effective or can be accompanied by serious side effects.
Approximately 200,000 people in the U.S. (and more than 1 million worldwide) are estimated to have sarcoidosis, an immune-mediated inflammatory disease that can affect any organ in the body, with about 90% of cases involving the lung.
About Namilumab
Granulocyte macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine over-expressed in several inflammatory diseases, including sarcoidosis. GM-CSF mediated pro-inflammatory signaling is thought to play a central role in recruitment of macrophages and monocytes to the lung and to trigger a granulomatous response, including the fusion of macrophages into multinucleated giant cells. Namilumab is an anti-GM-CSF monoclonal antibody formulated to be administered once-monthly as a subcutaneous injection being investigated for the treatment of pulmonary sarcoidosis.
MediaStephanie Leestephanie.Lee@roivant.Com
ILD, Pulmonary Sarcoidosis Burden Rose Significantly From 1990 To 2021
The increase in the global burden of interstitial lung disease (ILD) and pulmonary sarcoidosis had the greatest impact on countries with a high sociodemographic index.
The global burden of interstitial lung disease (ILD) and pulmonary sarcoidosis increased by 169% from 1990 to 2021, with the greatest impact observed in high sociodemographic index (SDI) countries, according to a study published in BMC Public Health.1
Characterized by varying degrees of inflammation or fibrosis, there are about 200 types of ILDs, with idiopathic pulmonary fibrosis being the most common. Patients with certain ILD types face a poor prognosis, with untreated survival typically ranging from 3 to 5 years post diagnosis.
In contrast, pulmonary sarcoidosis is a granulomatous lung disease of unknown origin that can lead to respiratory failure. Its progression is unpredictable, and treatment outcomes are often unsatisfactory.
Globally, respiratory diseases account for about one-third of the workload in primary health care facilities, contributing to the increasing burden of non-communicable diseases. The Global Alliance Against Chronic Respiratory Diseases aims to reduce this burden by addressing conditions like ILD and pulmonary sarcoidosis.
Given the prolonged disease course and poor prognosis associated with ILD and pulmonary sarcoidosis, the researchers emphasized the need to analyze trends in their global burden and correlations with social development. To address this, they conducted a comprehensive analysis of the Global Burden of Diseases Study (GBD) 2021, which assessed burden trends and examined SDI-related health inequalities from 1990 to 20212; the GBD 2021 data set included data on disability-adjusted life-years (DALYs) across 371 diseases and injuries.
The increase in the global burden of interstitial lung disease (ILD) and pulmonary sarcoidosis had the greatest impact on countries with a high socio-demographic index (SDI).Image Credit: flashmovie - stock.Adobe.Com
The researchers extracted DALY data for ILD and pulmonary sarcoidosis from 1990 to 2021, stratified by age, sex, year, location, and SDI.1 Data were obtained from 5 SDI quintiles (high, high-middle, middle, low-middle, and low), 21 GBD regions, and 204 countries/territories, across 20 age groups ranging from 5 or younger to 95 or older. DALYs were calculated by summing years lived with disability and years of life lost.
The SDI, a composite indicator of development status, combines per capita income, average education level, and fertility rates among females younger than 25. In this study, the SDI represented the development level of each country. Additionally, the researchers performed a decomposition analysis to explore DALY changes from 1990 to 2021, attributing observed differences to population size, epidemiological change, and population structure.
Health inequalities were assessed using the slope index of inequality (SII) and concentration index, representing the degree of absolute and relative inequalities, respectively. Using an appropriate regression model, the SII represented DALY differences between the countries with the highest SDI and those with the lowest SDI.
Conversely, the concentration index, a relative measure of inequality and positive values, indicated a concentration of DALYs among countries with high SDI. The researchers noted that greater absolute values of both the SII and concentration index indicate higher levels of inequality.
As measured in DALYs, the total burden of ILDs and pulmonary sarcoidosis was estimated at 4,042,150 (95% CI, 3,489,795-4,516,883) in 2021, an increase of 169.3% (95% uncertainty interval [UI], 134.8-218.2) from 1990. Therefore, the age-standardized DALY rate increased from 37.1 (95% UI, 30.6-45.4) per 100,000 in 1990 to 47.6 (95% UI, 41.3-53.2) in 2021.
Also, the researchers noted that males and those aged 70 to 74 experienced a higher burden of ILDs and pulmonary sarcoidosis; the DALY rates increased progressively with age. In particular, the high-SDI quintile showed the greatest increase in the age-standardized DALY rate from 1990 to 2021 (53.4%; 95% UI, 45.1-62.2).
Of the 21 GBD regions, South Asia (1,312,644; 95% UI, 890,806-1,740,639), high-income North America (582,575; 95% UI, 532,853-621,775), and Western Europe (526,090; 95% UI, 478,286-559,276) were most heavily affected in 2021. At the national level, India (1,124,248; 95% UI, 750,835-1,523,499), the US (524,808; 95% UI, 478,755-560,667), and Japan (383,903; 95% UI, 335,660-419,248) were the countries with the highest DALYs in 2021. However, the highest age-standardized DALY rate was observed in Peru (246.2 per 100,000; 95% UI, 178.3-317.8), while the lowest was in the Philippines (2.1 per 100,000; 95% UI, 1.5-2.6).
According to the decomposition analysis, there was a notable increase in ILDs and pulmonary sarcoidosis DALYs across the 5 SDI quintiles, with the largest increase observed in the high-SDI quintile. DALY increases due to population growth were most pronounced in the low-SDI (95.8%) and low-middle-SDI (51.3%) quintiles.
Based on the SII, the disparity in DALY rates between countries with the highest SDI vs those with the lowest SDI increased significantly, from 19.6 (95% CI, 11.6-27.5) in 1990 to 53.4 (95% CI, 39.7-67.1) in 2021. Therefore, countries with higher SDI experienced a higher burden of ILDs and pulmonary sarcoidosis. Lastly, the concentration index indicated relative inequality rose from 0.15 (95% CI, 0.08-0.21) in 1990 to 0.24 (95% CI, 0.16-0.32) in 2021.
The researchers acknowledged their limitations, one being that low-income countries lack accurate diagnostic tools and complete disease registries. Consequently, they may have underestimated the burden of ILDs and pulmonary sarcoidosis in low-income countries. Despite their limitations, the researchers expressed confidence in their findings, using them to suggest areas for further research.
"Future work should focus on obtaining more accurate and available epidemiological data on ILDs and pulmonary sarcoidosis, especially in low-income regions and countries," the authors concluded. "The economic burden of ILDs and pulmonary sarcoidosis should also be further studied."
References
Chen S, Li Y. Global health inequalities in the burden of interstitial lung disease and pulmonary sarcoidosis from 1990 to 2021. BMC Public Health. 2024;24(1):2892. Doi:10.1186/s12889-024-20430-y GBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133-2161. Doi:10.1016/S0140-6736(24)00757-8 Roivant Announces Topline Results From Phase 2 RESOLVE-Lung Study Of Namilumab In Chronic Active Pulmonary Sarcoidosis
Namilumab failed to show treatment benefit in patients with pulmonary sarcoidosis Further development of namilumab for the treatment of sarcoidosis will be discontinued BASEL, Switzerland and LONDON and NEW YORK, Dec. 03, 2024 (GLOBE NEWSWIRE) -- Kinevant Sciences, a clinical-stage biopharmaceutical company developing new medicines for rare inflammatory and autoimmune diseases, today announced its Phase 2 study failed to show treatment benefit in patients with chronic active pulmonary sarcoidosis. The Phase 2 RESOLVE-Lung study (NCT05314517) evaluated the efficacy and safety of namilumab, an investigational anti-GM-CSF monoclonal antibody administered once-monthly as a subcutaneous injection, in participants with chronic active pulmonary sarcoidosis.
Primary Endpoint Details: Namilumab failed to meet the primary endpoint of proportion of subjects with a Rescue Event during the double-blind period.
Secondary Endpoints Details: Secondary efficacy endpoints, including change in percent predicted forced vital capacity, corticosteroid tapering success, and change in the patient reported King's Sarcoidosis Questionnaire failed to show a treatment benefit consistent with the primary endpoint.
Safety Details: The safety profile of namilumab in RESOLVE-Lung remains similar to previous studies.
With these results, Kinevant will be discontinuing further development of namilumab for the treatment of sarcoidosis. Kinevant is committed to publishing the results of RESOLVE-Lung to inform future sarcoidosis research.
"Although RESOLVE-Lung failed to show a treatment benefit for namilumab, the significant amount of information produced by the study will be tremendously helpful to those in the field who are committed to improving the lives of sarcoidosis patients," said Bill Gerhart, CEO of Kinevant. "I would like to thank all the patients who courageously volunteered to participate in the study, as well as the Kinevant team, industry partners, principal investigators, site staff, and patient advocacy groups who all worked together to successfully conduct this important study for sarcoidosis."
"Risk-taking in clinical development is at the heart of our industry, and core to Roivant's mission of developing new medicines for patients in need. It's evident from our data that the RESOLVE-Lung study was thoughtfully designed and gave us a clear read on the potential benefits of namilumab in this patient population," said Matt Gline, CEO of Roivant. "Unfortunately science is sometimes humbling, and we are proud to have made the attempt, as well as of our successes in other programs this year. We look forward to taking calculated risks on similar programs in the future."
About RESOLVE-Lung
The RESOLVE-Lung study is a Phase 2 randomized, double-blind, placebo-controlled study of namilumab for the treatment of pulmonary sarcoidosis at sites in the U.S. And Europe. The study enrolled 107 patients with pulmonary sarcoidosis considered to have chronic, active disease not well-controlled despite available therapeutic options. Patients in the study received a once-monthly subcutaneous injection of namilumab or placebo (following the initial dosing period) for approximately six months. All patients who complete the 26-week double-blind treatment period were eligible to participate in a 28-week open-label extension treatment period on namilumab.
The primary endpoint of this study was proportion of subjects with a Rescue Event during the double-blind period. Rescue Event was defined as clinically significant worsening of a subject's sarcoidosis requiring treatment, failure to adhere to the protocol defined OCS taper, or premature discontinuation from the study associated with lack of benefit during the double-blind treatment period.
Study eligibility did not require subjects to be on high dose corticosteroids. If subjects were on >5mg/day of oral corticosteroid (OCS) at baseline, they were required to taper down to 5mg/day 8-10 weeks after randomization. If patients were on an immunosuppressive therapy (IST), they were required to stop the IST at randomization. Notably, all subjects enrolled had evidence of active pulmonary sarcoidosis disease, defined as a positive HRCT scan, significant lung inflammation on PET, and moderate to severe self-reported breathlessness.
About Sarcoidosis
Pulmonary sarcoidosis is a lung disease characterized by the presence of granulomas (clumps of immune cells) of unknown etiology that can cause breathlessness, fatigue, and pain. The resulting inflammation, if not effectively treated, can result in lung tissue scarring (fibrosis), lung dysfunction, and eventually lung failure. Approximately 50% of diagnosed patients require chronic therapy to treat symptoms and prevent progression. Oral steroids (e.G., prednisone) and off-label immunosuppressive therapies (e.G., methotrexate) are first- and second-line therapies respectively for sarcoidosis; however, these therapeutic options are often not effective or can be accompanied by serious side effects.
Approximately 200,000 people in the U.S. (and more than 1 million worldwide) are estimated to have sarcoidosis, an immune-mediated inflammatory disease that can affect any organ in the body, with about 90% of cases involving the lung.
About Namilumab
Granulocyte macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine over-expressed in several inflammatory diseases, including sarcoidosis. GM-CSF mediated pro-inflammatory signaling is thought to play a central role in recruitment of macrophages and monocytes to the lung and to trigger a granulomatous response, including the fusion of macrophages into multinucleated giant cells. Namilumab is an anti-GM-CSF monoclonal antibody formulated to be administered once-monthly as a subcutaneous injection being investigated for the treatment of pulmonary sarcoidosis.
About Roivant
Roivant is a biopharmaceutical company that aims to improve the lives of patients by accelerating the development and commercialization of medicines that matter. Roivant's pipeline includes IMVT-1402 and batoclimab, fully human monoclonal antibodies targeting FcRn in development across several IgG-mediated autoimmune indications; brepocitinib, a potent small molecule inhibitor of TYK2 and JAK1 in development for the treatment of dermatomyositis and non-infectious uveitis; and mosliciguat, an inhaled sGC activator in development for pulmonary hypertension associated with interstitial lung disease. We advance our pipeline by creating nimble subsidiaries or "Vants" to develop and commercialize our medicines and technologies. Beyond therapeutics, Roivant also incubates discovery-stage companies and health technology startups complementary to its biopharmaceutical business. For more information, www.Roivant.Com.
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MediaStephanie Leestephanie.Lee@roivant.Com
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