Vifor Pharma (United States)

We present a set of Grand Challenges for predictive modeling in small molecule drug discovery, with the goal of defining, prioritizing, and quantifying the areas where computation can have transformative impact. Rather than offering another broad survey of methods, this paper articulates specific scientific and technical problems that limit progress today and proposes measurable criteria by which advances can be judged. Our objective is to align researchers, investors, and industry leaders around the challenges that matter most for advancing real drug discovery programs. This work seeks to broaden participation in drug discovery by providing a clear roadmap for contributors from the growing areas of artificial intelligence, machine learning, robotics, high-performance computing, and quantum computing, where tools are rapidly advancing but are often disconnected from the practical realities of medicinal chemistry and pharmacology. The insights presented here draw on extensive discussions with experienced drug hunters, computational method developers, and thought leaders across biotech, pharma, software, and venture capital, as well as lessons learned from our own drug discovery efforts. While there is substantial enthusiasm (particularly around AI) for revolutionizing drug discovery, this moment demands sharper problem definition. Without clearly articulated challenges and performance metrics, computational innovation risks optimizing for benchmarks rather than for translational impact. We therefore identify Grand Challenges across four domains: Chemistry, Structure, Energy, and Pharmacology. For each domain, we present a common framework: a well-defined challenge, the underlying physical principles, its relevance to drug discovery decision-making, the current state of the field, and quantitative metrics that define progress. By grounding computational ambition in concrete scientific problems, we aim to catalyze sustained, measurable advances rather than episodic waves of enthusiasm.

ABSTRACTThe pivotal phase 3 trial MCI186‐19 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval. Study 19 utilized a targeted enrollment enrichment strategy based on post hoc analyses from earlier trials, selecting patients with higher baseline function, more rapid disease progression, and better respiratory status. To evaluate the generalizability of Study 19 results, subsequent post hoc analyses assessed the efficacy of edaravone in broader ALS populations. One machine learning‐based analysis retrospectively applied a validated model to Study 16 data, stratifying patients by predicted risk of respiratory decline. This detectable effect cluster analysis suggested that up to 70% of Study 16 participants may have benefited from edaravone. A second analysis investigated edaravone efficacy in patients from Study 19 with forced vital capacity (FVC) < 80% predicted (%p) at the start of treatment, since FVC ≥ 80%p was one of the Study 19 inclusion criteria. Both high‐ and low‐FVC subgroups demonstrated reduced ALS functional rating scale‐revised decline at 48 weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations.

BackgroundVisceral metastasis is prevalent among patients with advanced/metastatic breast cancer (ABC) and is a prognostic indicator of poor survival. We conducted a systematic literature review of the evidence for palbociclib plus endocrine therapy (ET) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) ABC and visceral metastasis.MethodsPubMed, EMBASE, Cochrane Library, and relevant conference proceedings were searched through September 2023. Phase 2/3 randomized clinical trials (RCTs) and real-world evidence (RWE) studies evaluating efficacy/effectiveness, safety, and health-related quality-of-life (QoL) of palbociclib plus ET were included.ResultsQualitative synthesis was conducted on 70 articles; 24 reported results from 8 RCTs; 46 were RWE studies. Data from >10,000 patients with visceral metastasis treated with palbociclib were included. All RCTs and RWE studies (5 each) that assessed palbociclib plus ET versus ET alone in patients with HR+/HER2− ABC and visceral metastasis showed significant reduction in risk of disease progression and/or death with palbociclib plus ET (34 %–50 % reduction in RCTs; 31 %–47 % in RWE studies). In RCTs, overall survival was not significantly different between the treatment groups; however, 4 of 5 RWE studies showed a significant benefit (36 %–42 % reduced risk of death) with palbociclib plus ET. Although data for other outcomes were limited, palbociclib plus ET was generally safe and well tolerated while QoL was maintained.ConclusionBoth RCTs and RWE studies consistently showed that palbociclib plus ET is efficacious/effective in patients with HR+/HER2− ABC and visceral metastasis; further research is warranted focused on safety, tolerability, and QoL in this patient group.

Many barriers exist that impact older adults abilities to access and manage medications. Senior PharmAssist is a nonprofit in Durham that provides medication management and access services to older adults. Here, we describe replication of Senior PharmAssists model in Buncombe, Guilford, and Pitt Counties and highlight learnings from each county.