Endoscopic Sleeve Gastroplasty Cost-Effective Than Semaglutide in Obesity Treatment: JAMA

A recent study determined that a minimally invasive bariatric procedure called Endoscopic Sleeve Gastroplasty (ESG) is more cost-effective than the latest weight-loss medication, semaglutide, for treating the individuals with class II obesity. This study was conducted from September 2022 to May 2023 which elucidates critical insights into the financial and health impacts of obesity treatments that emphasize the importance of cost in healthcare decisions. The key findings of this study were published in the recent edition of the Journal of American Medical Association.

The study deployed a Markov cohort model to compare the economic and health outcomes of ESG and semaglutide against a no-treatment strategy within the U.S. healthcare system. Adult patients with a body mass index (BMI) between 35 and 39.9 were focused in this analysis. The research centered on a hypothetical base case of a 45-year-old patient with a BMI of 37 undergoing either of the treatments.

ESG proved to achieve more substantial weight loss over a five-year period and demonstrated significant cost savings. The findings reveal that ESG had an incremental cost-effectiveness ratio (ICER) of -$595,532 per quality-adjusted life year (QALY), in common terms it saved more money while adding more quality life years when compared to semaglutide. Also, ESG added 0.06 QALYs and reduced the total healthcare costs by $33,583 relative to semaglutide.

Semaglutide is a glucagon-like peptide-1 receptor agonist and has been known for its efficacy in recent times but comes with a heavy price tag. Currently priced at $13,618 annually, this research suggests that to be on par with ESG, the cost of semaglutide would need to plummet to $3,591 per year which is a reduction by nearly threefold. The research employed rigorous statistical analyses to ensure the robustness of the outcomes observed. These analyses consistently supported the superior cost-effectiveness of ESG over the five-year horizon considered.

This study underlines the necessity for a strategic evaluation of treatment options in obesity management in light of the growing global adoption of various obesity treatments. The research advocates for a broader consideration of cost-effectiveness in public health decisions by highlighting the economic advantages of ESG and potentially influencing the policy changes moving forward. Healthcare providers, policymakers and patients may find these findings invaluable as they navigate the complex landscape of treatments available to manage obesity in a effective and economically sustainable way.

Reference:

Haseeb, M., Chhatwal, J., Xiao, J., Jirapinyo, P., & Thompson, C. C. (2024). Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss. In JAMA Network Open (Vol. 7, Issue 4, p. e246221). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.6221

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Chronic exercise tied to lower appetite in patients with type 2 diabetes: Study

Germany: A systematic review published in Nutrients has shed light on the impact of acute and chronic exercise on appetite and appetite regulation in patients with prediabetes or type 2 diabetes mellitus (T2DM).

The review of seven studies involving individuals with prediabetes or Type 2 diabetes found that chronic exercise may be associated with reduced appetite. The findings showed aerobic endurance exercise like brisk walking done consistently for 150 minutes weekly or more was most likely to lead to reduced hunger and increased satiety in participants diagnosed with diabetes.

The study results provided more evidence for an appetite-reducing rather than an appetite-increasing effect of (chronic) exercise on patients with prediabetes or T2DM.

Prediabetes and T2DM represent significant public health concerns globally, with their prevalence on the rise. Lifestyle interventions, including exercise, are important in managing these conditions. However, understanding the influence of exercise on appetite regulation in individuals with prediabetes or T2DM is crucial for optimizing treatment strategies.

Against the above background, Christoph Konitz, German Sport University Cologne, Cologne, Germany, and colleagues aimed to analyze the effects of acute and chronic exercise on appetite and appetite regulation in patients with abnormal glycemic control.

For this purpose, the researchers searched online databases for eligible studies. The included studies had to report assessments of appetite (primary outcome). Appetite-regulating hormone levels were analyzed as secondary outcomes (considered, if additionally reported).

Seven studies with a total of 211 patients with prediabetes or type 2 diabetes mellitus met the inclusion criteria.

The researchers reported the following findings:

  • Ratings of hunger, satiety, fullness, prospective food consumption, nausea, and desire to eat, as well as levels of (des-)acylated ghrelin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, pancreatic polypeptide, peptide tyrosine tyrosine, leptin, and spexin were considered.
  • Following acute exercise, the effects on appetite (measured up to one-day post-exercise) varied, there were either no changes or a decrease in appetite ratings following chronic exercise, both compared to control conditions (without exercise).
  • Inconsistent changes in appetite-regulating hormone levels accompanied these results. The overall risk of bias was low.

“The present results provide more evidence for an appetite-reducing rather than an appetite-increasing effect of (chronic) exercise on patients with T2DM or prediabetes,” the researchers wrote.

The researchers suggest that practitioners should, however, consider possible inter-individual differences in appetite responses to exercise.

“It is necessary to conduct studies on the effects of training interventions on appetite that also examine changes in free-living energy intake and components of energy expenditure to draw definite conclusions about the effectiveness of exercise in impacting long-term energy balance,” they concluded.

Reference:

Konitz, C., Schwensfeier, L., Predel, H., & Brinkmann, C. (2023). The Influence of Acute and Chronic Exercise on Appetite and Appetite Regulation in Patients with Prediabetes or Type 2 Diabetes Mellitus—A Systematic Review. Nutrients, 16(8), 1126. https://doi.org/10.3390/nu16081126

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Orally inhaled flecainide favorable for conversion of atrial fibrillation to sinus rhythm: Insights from INSTANT phase 2 trial

USA: Findings from the INSTANT phase 2 trial showed that orally inhaled flecainide passed muster for converting atrial fibrillation (AF) to sinus rhythm. The findings were published online in JACC: Clinical Electrophysiology on April 10, 2024.

INSTANT was an open-label, multicenter, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation to sinus rhythm.

The researchers reported that the risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable; suggesting that FlecIH could provide an effective, safe, and convenient first-line therapeutic option.

Atrial fibrillation is characterized by irregular and often rapid heart rate and poses substantial risks of stroke, heart failure, and other cardiovascular complications. While several pharmacological and interventional strategies exist for managing AF, achieving and maintaining sinus rhythm remains a cornerstone of therapy to mitigate associated morbidity and mortality.

Atrial fibrillation stands as one of the most prevalent cardiac arrhythmias worldwide, with its management presenting a significant challenge in clinical practice. Amidst this backdrop, the emerging use of orally inhaled flecainide offers a beacon of hope for restoring sinus rhythm in patients with AF.

Against the above background, Jeremy N. Ruskin, Cardiac Arrhythmia Service GRB 8, Massachusetts General Hospital, Boston, Massachusetts, USA, and colleagues aimed to investigate the safety and efficacy in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. The mean age of the patients was 60.5 years, the mean body mass index was 27.0 kg/m2, and 34.7% were women.

Patients self-administered flecainide acetate oral inhalation solution over 8 minutes, using a breath-actuated nebulizer, in a supervised medical setting and were continuously monitored for 90 minutes using a 12-lead Holter.

The researchers reported the following findings:

· All patients had ≥1 AF-related symptom at baseline, and 87.8% had AF symptoms for ≤24 hours.

· The conversion rate was 42.6% with a median time to conversion of 14.6 minutes.

· The conversion rate was 46.9% in a subpopulation that excluded predose flecainide exposure for the current AF episode.

· Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5.

· In the conversion-no group, 81.5% of patients underwent electrical cardioversion by day 5.

· The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration.

In conclusion, the risk-benefit of orally inhaled flecainide acetate for acute cardioversion of recent-onset AF is favorable and could provide an effective, safe, and convenient first-line therapeutic option for the conversion of recent-onset AF.

“The delivery of flecainide by oral inhalation in the hospital/ED setting holds the potential to provide a rapid and practical treatment, reducing rates of hospitalization and health care costs,” the researchers wrote. “There is a need for further studies to confirm the current study findings on the clinical effectiveness and safety of inhaled flecainide.”

Reference:

Ruskin JN, Camm AJ, Dufton C, Woite-Silva AC, Tuininga Y, Badings E, De Jong JSSG, Oosterhof T, Aksoy I, Kuijper AFM, Van Gelder IC, van Dijk V, Nuyens D, Schellings D, Lee MY, Kowey PR, Crijns HJGM, Maupas J, Belardinelli L; INSTANT Investigators. Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial. JACC Clin Electrophysiol. 2024 Mar 26:S2405-500X(24)00164-6. doi: 10.1016/j.jacep.2024.02.021. Epub ahead of print. PMID: 38613545.

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KIMS Hospital unveils state-of-the-art stroke centre

Bhubaneswar: Kalinga Institute of Medical Sciences (KIMS) recently announced the grand opening of its new comprehensive Stroke Center, providing the region with cutting-edge resources to combat the devastating effects of stroke. The center offers a dedicated team of stroke specialists, the latest in diagnostic and treatment technologies, and a commitment to rapid, patient-centered care.  

“Stroke is a time-critical medical emergency, these patients need to reach the hospital within 4 and half hours of stroke, to prevent maximum damage to the brain,” said Dr. Santosh Ku Dash, Associate professor and head of Neurology, KIMS. This new Stroke Center ensures our patients have access to the most advanced care available, delivered by experts who understand the urgency of stroke treatment. With every minute saved, we increase the chances of a positive outcome.”       

Also Read:Boehringer Ingelheim India joins hands with Maharashtra Govt to strengthen stroke care in state

The KIMS Hospital Stroke Center offers a full spectrum of advanced stroke care. This includes 24/7 access to stroke specialists, rapid diagnostic imaging (such as CT scans and MRIs), timely administration of clot-busting medications, and minimally invasive clot removal procedures when necessary. Patients also benefit from a specialized stroke unit with expert care and comprehensive rehabilitation programs focused on regaining function and independence.  

“The opening of this Stroke Center is a major step forward for healthcare in Odisha. We’re proud to offer this vital service, giving stroke patients the best possible chance of recovery. We extend our sincere gratitude to Dr. Achyuta Samanta, founder of KIIT, for his unwavering support in making this a reality. KIMS Hospital is a leading healthcare provider in Odisha, committed to delivering exceptional medical care across a wide range of specialities.  

Also Read: Patients with persistently high BP within 24 hours of ischemic stroke onset at highest risk of adverse outcomes: Study

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Hemoglobin Levels Predict Kidney Disease Progression in Diabetes Patients, suggests study

A recent study published in the journal of Diabetes, Metabolic Syndrome and Obesity unveiled critical insights into the role of hemoglobin levels in predicting the progression of diabetic kidney disease (DKD) which is a condition that significantly impacts millions of people globally. This research was conducted on a total of 815 patients with DKD from January 2010 to January 2023 that highlights the intricate relationship between hemoglobin levels and the risk of worsening kidney function, especially in the context of anemia, a common complication of diabetes.

The study by Chen X and team employed a meticulous retrospective cohort analysis to probe the depths of this association. After utilizing advanced statistical models that included Cox proportional hazard regression, this research highlighted on how varying hemoglobin levels influence the renal outcomes, specifically the decline in glomerular filtration rate (GFR) which is a critical measure of kidney function.

The participants were of the average age of 56 years, where males constituted to a 65.4% of the group. The findings revealed that for every unit increase in hemoglobin levels, the risk of reaching the defined renal composite endpoint included a 50% reduction in GFR or the onset of end-stage renal disease (ESRD) that decreased significantly.

A particularly intriguing aspect of the study was the discovery of a nonlinear relationship between hemoglobin levels and the outcomes of kidney health, with an inflection point identified at 109 g/L. This suggests that the protective effect of increased hemoglobin levels on kidney function becomes more pronounced beyond this threshold.

Moreover, the research underscored a gender-specific impact, with male patients showing a more significant association between higher hemoglobin levels and better renal prognosis. This finding could pave the way for tailored treatment strategies that consider the unique physiological differences between genders.

The implications of this study are surplus and positive especially in the population where diabetes remains a leading cause of kidney disease. The identification of hemoglobin as a predictive marker for DKD progression offers the clinicians a valuable tool to manage this complex condition and also emphasize the importance of maintaining optimal hemoglobin levels in diabetic patients.

Reference:

Chen, X., Xie, J., Zhang, Y., Zhang, S., Li, S., Lu, M., Liu, D., He, W., Yau, H., Jia, R., Zhu, Y., & Wang, W. (2024). Prognostic Value of Hemoglobin Concentration on Renal Outcomes with Diabetic Kidney Disease: A Retrospective Cohort Study. In Diabetes, Metabolic Syndrome and Obesity: Vol. Volume 17 (pp. 1367–1381). Informa UK Limited. https://doi.org/10.2147/dmso.s452280

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Erenumab: A Potential Breakthrough in Rosacea Management

Denmark: A nonrandomized controlled trial showed the importance of the calcitonin gene-related peptide (CGRP) pathway in the pathophysiology of erythema and flushing in rosacea. The findings suggested that calcitonin gene-related peptide receptor inhibition holds potential in treating rosacea-associated erythema and flushing.

“The study comprising 30 individuals with rosacea-associated flushing and erythema found that subcutaneous injections of monoclonal antibodies against the calcitonin gene-related peptide receptor administered every four weeks for 12 weeks significantly decreased days with erythema and flushing by weeks 9 through 12 compared with baseline,” the researchers reported. The findings were published online in JAMA Dermatology on April 17, 2024. 

Rosacea is characterized by facial redness, visible blood vessels, and in some cases, papules and pustules. Persistent erythema and flushing are hallmark features, often resistant to conventional therapies. This affects patients’ physical appearance and psychological well-being, highlighting the need for effective treatment options.

While several treatment modalities exist, managing these symptoms remains a challenge. However, recent research suggests a promising avenue with erenumab use, a monoclonal antibody targeting CGRP. Nita K. F. Wienholtz, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark, and colleagues aimed to examine the tolerability, effectiveness, and safety of erenumab, an anti–CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing.

For this purpose, the researchers conducted a single-center, open-label, single-group, nonrandomized controlled trial between 2020 and 2021. Eligible participants included patients with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. Throughout the study period, no concomitant rosacea treatment was allowed.

Participants received 140 mg of erenumab subcutaneously every four weeks for 12 weeks. At week 20, a safety follow-up was performed. A total of 30 participants (mean age, 38.8 years; 77% females were included, of whom 27 completed the 12-week study.

The primary outcome was a mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The secondary outcome was a mean change in the number of days with moderate to severe erythema. Adverse events were recorded for patients who received at least one dose of erenumab.

Following were the study’s key findings:

  • There was a reduction in the mean number of days with moderate to extreme flushing by −6.9 days from 23.6 days at baseline.
  • There was a reduction in the mean number of days with moderate to severe erythema by −8.1 days from 15.2 days at baseline.
  • Adverse events included transient mild to moderate constipation (33% of participants), transient worsening of flushing (13% of participants), bloating (10% of participants), and upper respiratory tract infections (10% of participants), consistent with previous data.
  • One participant discontinued the study due to a severe adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time.

In conclusion, the findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data). The study also showed that CGRP-receptor inhibition holds potential in treating flushing and erythema associated with rosacea.

“Larger randomized clinical trials are needed to confirm this finding,” the researchers wrote.

Reference:

Wienholtz NKF, Christensen CE, Do TP, et al. Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea: A Nonrandomized Controlled Trial. JAMA Dermatol. Published online April 17, 2024. doi:10.1001/jamadermatol.2024.0408

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Advancements in detecting interstitial lung disease in rheumatoid arthritis: Thoracic ultrasound takes the lead

Denmark: Systematic screening for respiratory symptoms combined with thoracic ultrasound (TUS) can reduce the diagnostic delay of interstitial lung disease (ILD) in rheumatoid arthritis (RA), a recent study published in Arthritis Care & Research has shown.

“To our knowledge, this prospective study is the first to use respiratory symptoms in rheumatoid arthritis as inclusion criteria,” the researchers wrote. TUS offers several advantages, including its non-invasive nature, absence of radiation exposure, and cost-effectiveness.

Rheumatoid arthritis is a chronic autoimmune disorder primarily affecting the joints, but it can also have systemic manifestations, including ILD. Early detection of ILD in RA is crucial for timely intervention and management. Traditional diagnostic methods, such as chest X-rays and high-resolution computed tomography (HRCT), have limitations, including radiation exposure and cost. However, a recent study suggests that thoracic ultrasound could revolutionize the detection of ILD in RA patients.

Against the above background, Bjørk K. Sofíudóttir, PUlmo-RhEuma Frontline Center (PURE), Department of Rheumatology Odense University Hospital, Odense, Denmark, and colleagues aimed to determine the diagnostic accuracy of thoracic ultrasound for detecting interstitial lung disease in rheumatoid arthritis with respiratory symptoms.

For this purpose, the researchers systematically screened individuals with RA visiting Rheumatological outpatient clinics in the Region of Southern Denmark for cough, dyspnoea, recurrent pneumonia, prior severe pneumonia, or a chest X-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included.

Individuals were not eligible if they had a chest HRCT <12 months or were already diagnosed with ILD. A blinded TUS expert evaluated thoracic ultrasound, and TUS was registered as positive for ILD if ≥10 B-lines or bilateral thickened and fragmented pleura were present.

The study’s primary outcomes were TUS’s specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV). HRCT was assessed by an ILD-specialised thoracic radiologist, followed by a multidisciplinary team discussion. The accepted window of HRCT was <30 days after TUS was performed.

The key findings of the study were as follows:

  • 77 participants received HRCT <30 days after TUS, and 30% were diagnosed with ILD.
  • TUS had a sensitivity of 82.6% and a specificity of 51.9%, corresponding to a PPV of 42.2% and an NPV of 87.5%.

In conclusion, this prospective study is the first to use respiratory symptoms in rheumatoid arthritis as inclusion criteria. Systematic screening for respiratory symptoms combined with thoracic ultrasound can reduce the diagnostic delay of interstitial lung disease in rheumatoid arthritis.

Reference:

Sofíudóttir, B. K., Harders, S., Laursen, C. B., Lage-Hansen, P. R., Nielsen, S. M., Just, S. A., Christensen, R., Davidsen, J. R., & Ellingsen, T. Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound. A Diagnostic Test Accuracy study. Arthritis Care & Research. https://doi.org/10.1002/acr.25351

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Admission blood sugar independent predictor of coagulopathy in multiple Trauma Patients, finds study

Admission blood sugar independent predictor of coagulopathy finds study published in the European Journal of Trauma and Emergency Surgery

Coagulopathy is prevalent in multiple trauma patients and worsens bleeding complications, leading to higher morbidity and mortality rates. Hyperglycemia upon admission predicts hemorrhagic shock and mortality in severely injured patients. This study aimed to assess admission glucose levels as an independent prognostic factor for coagulopathy in multiple injured patients. This retrospective cohort study observed multiple trauma patients treated at a level I trauma center between January 1, 2005, and December 31, 2020. Coagulopathy was defined as an international normalized ratio (INR) > 1.4 and/or activated thromboplastin time (APTT) > 40 s. Analysis of variance compared clinical and laboratory parameters of patients with and without coagulopathy. Receiver-operating-characteristic (ROC) and multivariate logistic regression analyses identified risk factors associated with coagulopathy. RESULTS: The study included 913 patients, of whom 188 (20%) had coagulopathy at admission. Coagulopathy patients had higher mortality than those without (26% vs. 5.0%, p < 0.001). The mean glucose level in coagulopathy patients was 10.09 mmol/L, significantly higher than 7.97 mmol/L in non-coagulopathy patients (p < 0.001). Admission glucose showed an area under the curve (AUC) of 0.64 (95% CI [0.59-0.69], p < 0.001) with an optimal cut-off point of 12.35 mmol/L. After adjusting for other factors, patients with high admission glucose had a 1.99-fold risk of developing coagulopathy (95% CI 1.07-3.60). Other laboratory parameters associated with coagulopathy included haemoglobin, bicarbonate (HCO3), and lactate levels. This study emphasizes the significance of admission blood glucose as an independent predictor of coagulopathy. Monitoring hyperglycemia can aid in identifying high-risk patients.

Reference:

Mayor, Jorge, et al. “Do Admission Glucose Levels Independently Predict Coagulopathy in Multiple Trauma Patients? A Retrospective Cohort Analysis.” European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society, 2024.

Keywords:

Admission blood sugar, independent predictor, coagulopathy, Mayor, Jorge, European Journal of Trauma and Emergency Surgery

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Subconjunctival injection of triamcinolone acetonide may prevent complications after phacoemulsification: Study

In recent research conducted by Kaiser Permanente Northern California, a single injection of triamcinolone acetonide (TA) was identified to be more effective and safer than traditional topical prednisolone acetate (PA) in preventing complications following cataract surgery. The findings were published in the Ophthalmology journal.

This retrospective study spanned from 2018 to 2021 and included 69,832 patient-eyes which underwent phacoemulsification to remove cataract. The patients were categorized into groups receiving either topical PA with or without a nonsteroidal anti-inflammatory drug (NSAID) or a subconjunctival injection of TA, at varying doses and concentrations. The effectiveness of these treatments was evaluated based on the incidence of postoperative macular edema (ME) and iritis and the safety was assessed via the occurrence of glaucoma-related events within a year following the surgery.

The results highlighted that the high-dose TA (10 mg/mL) group showed a statistically significant reduction in the risk of developing postoperative ME when compared to the group treated with topical PA. The odds ratio (OR) was 0.64 which suggests a 36% lower risk and provides promising insight into the potential benefits of opting for an injection over topical solutions. Further, the combination of PA and NSAID did not show a statistically significant benefit in reducing ME.

This study observed trends in the reduction of postoperative iritis in patients who were treated with high concentration TA (40 mg/mL), although these findings did not reach statistical significance. The low dose TA (10 mg/mL) group experienced markedly lower odds of encountering glaucoma-related events when compared to the topical PA group by indicating a safer profile for this particular injection dosage.

Higher doses of TA at 40 mg/mL were associated with an elevated risk of glaucoma-related events which suggesting that while effective, the higher concentrations of the drug might increase the risk of adverse effects. This underlines the importance of dose management in the use of injectable steroids to balance efficacy and safety.

This  findings are significant as they could influence future protocols in the management of inflammation and prevention of complications post-cataract surgery. The subconjunctival injections of TA with optimized dosages lower risks of ME and iritis and might become a preferred strategy over the conventional topical treatments. This offers a simpler and potentially more effective prophylactic option for the patients who undergo cataract surgery every year.

Reference:

Shorstein, N. H., McCabe, S. E., Alavi, M., Kwan, M. L., & Chandra, N. S. (2024). Triamcinolone Acetonide Subconjunctival Injection as Stand-alone Inflammation Prophylaxis after Phacoemulsification Cataract Surgery. In Ophthalmology. Elsevier BV. https://doi.org/10.1016/j.ophtha.2024.03.025

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FDA fast tracks enibarcimab for the treatment of septic shock

 It is believed that modulation of ADM pathway may improve outcomes in patients with septic shock.

The Food and Drug Administration has granted Fast Track designation to enibarcimab for management of septic shock. Enibarcimab is a first-in-class non-neutralizing monoclonal antibody that binds to adrenomedullin (ADM), a vasoprotective hormone.

AdrenoMed is now preparing a confirmatory Phase IIb/III clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing a precision medicine approach.

AdrenoMed’s CEO Dr. Richard Jones commented: “We are very pleased that enibarcimab has received Fast Track designation from the FDA, recognizing its potential as an innovative biomarker-guided treatment against septic shock to fill the unmet medical need in this very serious condition with a high death toll. This is a great confirmation of AdrenoMed’s efforts to reduce patient heterogeneity and develop effective treatments by bringing precision medicine also to intensive care units.”

Enibarcimab is a non-blocking antibody binding to the vasoprotective hormone adrenomedullin. Applying AdrenoMed’s precision medicine approach, enibarcimab treatment of patients with septic shock resulted in improved organ dysfunction and a relevant reduction of day 28 all-cause mortality from 24% to 8% in the patient population defined by the two biomarkers adrenomedullin and DPP3 in the AdrenOSS-2 trial.

With a mortality rate of 20-30% for sepsis and 30%-50% for septic shock in developed countries, sepsis represents an enormous public health burden and is responsible for almost 20% of all deaths worldwide.

Fast Track is a process designed by the FDA to facilitate the development of promising drugs for the treatment of serious conditions that fill an unmet medical need and to accelerate review by the regulatory authority, aimed at getting important new drugs to the patient earlier. A drug that receives Fast Track designation is eligible for more frequent meetings with FDA to discuss development plans for the drug regarding collection of data needed to support its approval; more frequent communication about such things as the design of the proposed clinical trials and use of biomarkers; eligibility for Accelerated Approval and Priority Review, if relevant criteria are met; and Rolling Review.

Dr. Stephan Witte, CMO of AdrenoMed, said: “We are very confident that the use of enibarcimab in combination with two biomarkers, Adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3), holds the promise to become the first effective targeted treatment against septic shock. With AdrenoMed’s biomarker-guided approach it is possible to clearly define the patient population benefitting most from enibarcimab, resulting in a more pronounced treatment effect and leading to improved mortality in septic shock.”

This was the conclusion also drawn by Prof. Peter Pickkers from the Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands, in a poster session during the recent ISICEM 2024, which took place in Brussels, Belgium, from March 19 – 22, 2024, where he presented previously unpublished data from a prespecified subgroup of the AdrenOSS-2 trial.

About AdrenOSS-2

The double-blind, randomized, placebo-controlled, biomarker-guided Phase II trial AdrenOSS-2 (n = 301) had included a prespecified analysis of the role of cDPP3 as a second biomarker (next to ADM) to exclude patients who are unlikely to respond to enibarcimab treatment.

DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of cDPP3 indicate a high risk of organ dysfunction and mortality. This pathway is mechanistically independent from the loss of vascular integrity, which is known to be the main driver of mortality in septic shock and is indicated by elevated plasma levels of ADM (>70 pg/mL). Consequently, the aim of additional analyses was to investigate the impact of different cDPP3 levels on the treatment effect (28-day all-cause mortality) and to identify a suitable cut-off level.

It was shown that the effect of enibarcimab on mortality improves with lower cDPP3 values and that the patients with elevated ADM, but non-elevated baseline cDPP3 (below the upper normal range, ≤ 30-50 ng/mL), benefitted the most from enibarcimab treatment. At 28 days, this patient subgroup had a statistically significant >60% relative reduction in mortality compared to placebo.

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