Promentis Pharmaceuticals (United States)

Abstract Background Heart failure (HF) is one of the leading public health issues worldwide. Current guidelines recommend HF treatment using different drug classes depending on ejection fraction (EF) and underlying cause of HF. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a drug class with a class IA recommendation in the current ESC-guidelines for HF treatment independent of EF. The SGLT2i dapagliflozin is approved for treatment of HF across the entire spectrum of EF in Germany. However, real-world data are limited. Purpose The aim of EVOLUTION-HF DEallEF is to generate data on real-world dapagliflozin use in HF patients independently of EF in Germany under the multinational umbrella EVOLUTION-HF study protocol. Methods EVOLUTION-HF DEallEF is a non-interventional, prospective, longitudinal cohort study. It is planned to enrol a total of 1000 patients with chronic HF in Germany, including 40% patients with preserved (HFpEF; EF ≥ 50%), 20% with mildly reduced (HFmrEF; EF 41-49%), and 40% with reduced EF (HFrEF; EF ≤ 40%). Patients willing to participate, aged ≥18 years, who started dapagliflozin treatment 14 to 90 days prior to enrolment according to the local product label, are eligible for participation. Among reasons for exclusion is previous SGLT2i treatment (including dapagliflozin). Data on medical history, clinical symptoms, previous and concomitant medication and patient-reported outcomes (PROs) are collected. EVOLUTION-HF DEallEF has included its first patient in 04/2024 and is currently open for enrolment. Interim analyses (IA) were planned at predefined timepoints (after 250, 500 enrolled patients and enrolment completion). The three different EF cohorts (HFpEF, HFmrEF, HFrEF) are analysed separately and as a total population. Only descriptive statistical methods are used. Results This 1st IA (data cutoff: 02/12/2024) included 249 patients in the safety set (all patients received at least one dose of dapagliflozin, one patient refused data usage) and 244 patients who fulfilled all eligibility criteria in the full analysis set (FAS). Patients were enrolled in 31 study sites, mainly in office-based cardiologic practices. In the FAS, distribution of patients to HF cohorts was 51% with HFpEF (n=125), 30% with HFmrEF (n=73), and 19% with HFrEF (n=46). Conclusions Patients’ and disease characteristics observed at the time of the first IA are in range with previously published data indicating that a representative cohort of patients newly treated with dapagliflozin for HF are enrolled in EVOLUTION-HF DEallEF. Dysbalance in expected enrolment proportion per EF cohort is mainly caused by exclusion of patients with SGLT2i-pretreatment. The study aims to provide further insights into real-world dapagliflozin treatment for HF in Germany, focussing on clinical and patients’ perspective.

Introduction Preclinical animal experiments and initial feasibility studies in humans have shown encouraging outcomes using the novel Saccular Endovascular Aneurysm Lattice (SEAL™) system for the treatment of both ruptured and unruptured wide‐neck intracranial aneurysms (IAs). The SEAL™ Interventional Pivotal IDE PMA Trial (SEAL™ IT) is designed to assess the safety and efficacy of the SEAL™ in patients with saccular IAs. This ongoing, prospective, multicenter trial includes three study arms and will enroll a total of 279 participants with wide‐neck bifurcation (WNBA), sidewall (SW), or acutely ruptured IAs across 50 U.S. sites. Methods Eligibility requirements include patients aged 20‐80 years with a wide‐neck saccular intracranial aneurysm (2‐19 mm) deemed suitable for treatment with the SEAL™ Intrasaccular Device (SID). Participants receive treatment using the SEAL™ device (Galaxy Therapeutics Inc.) and are monitored at discharge, and again at 3, 6, and 12 months, followed by yearly assessments for up to 5 years. The primary efficacy outcome is defined as complete aneurysm occlusion at 12 months without evidence of parent vessel stenosis or the need for retreatment, as determined by an independent core laboratory. Key safety outcomes include neurological death within 12 months, stroke occurring within the first 30 days, and ipsilateral stroke between 30 days and 1 year. Results As of submission, 163 WNBA, 58 WNSW, and 33 ruptured for a total of 254 patients (76.3% female; mean age 61.7 ± 11.3) have been enrolled at 50 sites. Mean aneurysm width was 5.2 ± 2.1, neck size of 3.7 ± 1.4, and neck‐to‐dome ratio of 1.4 ± 0.32. SEAL Arc was used in 63.6% and SEAL Base in 36.4%. Technical device success rate is 100% for WNBA, 94.8% WNSW, and 97.0% ruptured. The interim complete occlusion rate for the primary group is 84.5% at most recent date based on available imaging. Conclusion Preliminary data for the SEAL™ intrasaccular device is promising; Safety and effectiveness updates will be presented at the SVIN Conference.

How do you balance the need for continuous learning and skill development with the demands of client work? What resources or strategies do you use to stay updated on industry trends and advancements? How do you manage multiple projects with overlapping deadlines? What project management tools or techniques do you find most effective? How do you determine your hourly rate or project fee? What factors do you consider when setting your pricing? In this issue, our Freelance Focus contributors are: Cathryn D. Evans Gail Flores Alex Howson

Introduction. The most common extragenital pathology during pregnancy includes upper and lower respiratory tract infections (URTI and LRTI), which, if left untreated, leading to obstetric and perinatal pathology. It is relevant to conduct pharmacoepidemiological studies assessing the preferences of specialists regarding the treatment of pregnant women and attitudes towards vaccination in real clinical practice.Aim. To analyze approaches to pharmacotherapy of URTI and LRTI in pregnant women, evaluate the compliance of prescribed drugs with current clinical recommendations and treatment standards.Materials and methods. The study was conducted from 2018 to 2022 using an anonymous questionnaire method in seven regions of Russia.Results and discussion. A total of 227 physicians from seven regions of Russia were surveyed, with 66.8% being internal medicine doctors and 33.2% obstetrician-gynecologists. This study revealed that physicians’ knowledge regarding the rational use of antimicrobial drugs (AMD) in pregnant women is insufficient. Respondents showed better results in the use of AMD in the treatment of pneumonia, with 78.7% of surveys indicating correct tactics. The worst results were observed in answering the question about the appropriateness of prescribing AMD for URTI, tracheitis, and bronchitis (40.3% to 67.7% of respondents made incorrect choices). Overall, 57.7% of respondents understand the importance of vaccination among pregnant women.Conclusion. The results of the conducted study indicate that the choice of drugs for the therapy of URTI and LRTI, especially AMD, for outpatient treatment of pregnant women in some situations does not fully correspond to the current clinical recommendations in our country. Moreover, it is particularly concerning that some physicians prescribe drugs that are unsafe for pregnant women or lack the necessary evidence base or indications for use.

IntroductionMechanical thrombectomy using stent retrievers and aspiration techniques has emerged as the standard of care for patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (LVO). This study intended to collect real‐world clinical evidence on the safety and effectiveness of endovascular treatment of AIS using the SOFIA Flow Plus 6F aspiration catheter. The primary endpoint was the proportion of subjects achieving mTICI ≥2b. Secondary endpoints included good functional outcomes (mRS 0‐2) at Day 90, revascularization time, first line and first pass mTICI ≥2b, occurrence of procedure‐related SAEs, vasospasm involving the accessed vascular tree, embolization to new territories (ENTs), symptomatic intracerebral hemorrhage (sICH) within 24 hours and mortality at Day 90.MethodsSOFAST was a prospective, multicenter, single‐arm, observational post‐market study. The enrolled subjects were ≥21 and ≤85 years with large vessel (ICA or MCA) proximal occlusion, pre‐morbid mRS ≤1, baseline NIHSS ≥5, and for whom groin puncture was within 8 hours of symptom onset. A total of 108 patients were enrolled and treated using aspiration thrombectomy with SOFIA 6F as the first line treatment device. Patients were followed at 24 hours, 7 days/discharge, and 90 days post‐procedure. Cerebral angiography was performed pre‐ and post‐procedure. Clinical assessments included the NIHSS and mRS scales. All neurological, device‐related, and procedure‐related AEs and deaths were adjudicated by independent medical reviewers. Angiographic and other imaging data was adjudicated by an independent core laboratory.ResultsA total of 108 subjects were enrolled (mean age 62.7 years, 50% men) with a median NIHSS of 15.5. Of 108 subjects, 97.2% (105/108), 85.2% (92/108) and 55.6% (60/108) achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. With first line aspiration using SOFIA 6F, 87.0%, 79.6% and 52.8% achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. Median number of passes was one (range 1‐3). First pass rate of mTICI 2c or 3 using SOFIA 6F was 70.4%, of which 50.9% patients achieved mTICI score of 3. Mean duration from groin puncture to initial clot contact was 13.0 min and to successful revascularization was 17.9 min.Good functional outcome was achieved in 66.7% (72/108) of subjects at Day 90 (mRS 0‐2), procedure‐related SAEs occurred in 2.8% (3/108) of subjects and sICH in 0.9% (1/108) of subjects within 24 hours. Procedural vasospasm was recorded in in 9.3% (10/108) of subjects, and mortality in 7.4% (8/108) subjects at Day 90 (none related to the study device). No ENTs occurred.ConclusionIn SOFAST study, mTICI ≥2b revascularization was achieved in the majority of patients at the end of all procedures (97.2%) and with first line treatment (87.0%) with a large fraction of these subjects achieving mTICI ≥2c following the first SOFIA 6F pass (70.4%). Durations from groin puncture to clot contact and successful revascularization were relatively short. The study presented high rates of good functional outcome at Day 90 and low rates of safety events. In summary, the study provides encouraging evidence of the safety and effectiveness of the SOFIA 6F device for aspiration thrombectomy in acute ischemic stroke subjects.

BackgroundENCORE, an observational, prospective, open‐label study, investigated real‐world treatment practices and outcomes with cetuximab plus platinum‐based therapy (PBT) in first‐line (1L) recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).AimsThis multinational study aimed to investigate the long‐term use of cetuximab plus PBT for 1L R/M SCCHN in a clinical setting. In particular, this study aimed to explore clinical considerations such as the decision to prescribe cetuximab plus PBT in R/M SCCHN, the mode and duration of treatment, and patient outcomes.Methods and ResultsPreviously untreated patients with R/M SCCHN whose planned treatment was cetuximab plus PBT were enrolled from 6 countries. Among 221 evaluable patients, planned treatments included cetuximab plus carboplatin (31.2%), cisplatin plus 5‐fluorouracil (31.7%), or carboplatin plus 5‐fluorouracil (23.1%); 3.2% included a taxane, and 45.2% did not include 5‐fluorouracil. Cetuximab treatment was planned for a fixed duration (≤24 weeks) in 15 patients (6.8%) and until disease progression in 206 (93.2%). Median progression‐free survival and overall survival were 6.5 and 10.8 months, respectively. Grade ≥3 adverse events occurred in 39.8% of patients. Serious adverse events occurred in 25.8% of patients; 5.4% were cetuximab‐related.ConclusionIn patients with R/M SCCHN, first‐line cetuximab plus PBT was feasible and modifiable in a real‐world setting with similar toxicity and efficacy as in the pivotal phase III EXTREME trial. Clinical trial registration number: EMR 062202‐566.

Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. 67 hospitals in the United States. Adults with COVID-19 admitted to a participating ICU. Time to death, censored at hospital discharge, or date of last follow-up. Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Observational design. Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. None.

Abstract Background Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC. Methods In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score. Results 470 patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (-2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (-7.82 vs. non-responders − 1.97, p = 0.0005). The VAS for pain (-16.37 vs. non-responders − 8.89, p = 0.001) and swallowing of solid food (-16.67 vs. non-responders − 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05–1.20, p = 0.0009) Conclusion In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.