How political conflicts and a lack of coordination hampered Brazil’s vaccine rollout

Rows between Brazilian leaders slowed down Brazil’s vaccination programme, but the regulatory process and lengthy negotiations over technology transfers also played a part. Elize Massard da Fonseca and Ken Shadlen (LSE) look at the lessons for other middle-income countries

Promoting and regulating generic medicines: Brazil in comparative perspective

Generic drug substitution may constitute a core instrument of countries’ National Pharmaceutical Policies, a way to reduce the price of drugs while expanding access to health care. Despite the potential importance of policy in this area and observed differences in national practices, scholars embarking on comparative analysis lack a roadmap of which dimensions of generic drug policy to assess and compare. We consider countries’ rules and regulations across four dimensions: (1) the demonstration of therapeutic equivalence, (2) pharmaceutical packaging and labelling, (3) drug prescription, and (4) drug substitution. We maintain that to be able to understand and compare national approaches toward generic drug promotion, it is crucial to carefully distinguish among these four dimensions. Furthermore, we suggest that analysis must also consider how the diverse interests of actors in public and private sectors shape the design and implementation of generic drugs policies. To illustrate both the dimensions of policy and the conflicts around generics policies, we focus on the case of Brazil

Investigation of juncture stress fields in multicellular shell structures

Discontinuity stress fields in thin elastic multicellular shell structures subject to inertial, pressure, and thermal loadin

Integrating science, technology and health policies in Brazil: incremental change and public health professionals as reform agents

Brazil has encouraged an ambitious set of policies toward the pharmaceutical industry, aiming to foster technological development while meeting health requirements. We characterize these efforts, labeled the “Health-Industry Complex” (Complexo Industrial da Saúde, CIS), as an outcome of incremental policy change backed by the sustained efforts of public health professionals within the federal bureaucracy. As experts with a particular vision of the relationship between health, innovation, and industry came to dominate key institutions, they increasingly shaped government responses to emerging challenges. Step by step, these professionals first made science and technology essential aspects of Brazil’s health policy, and then merged the Ministry of Healths’s new focus on science, technology, and health, with industrial policy measures aimed toward private firms. We contrast this depiction of these policy changes with a conventional view that relies on partisan orientation of the Executiv

Vaccine technology transfer in a global health crisis: actors, capabilities, and institutions

The COVID-19 pandemic, which featured international pharmaceutical firms seeking to build global manufacturing networks to scale-up the supply of vaccines, has generated heightened interest in understanding the role of firm-to-firm technology transfer. While considerable attention has been given to tracking the extent of international vaccine technology transfer, we know little about how partnerships were established and work in practice. Understanding the challenges that such projects face, and how such challenges may be overcome, is crucially important. This paper provides an account of the partnership between the British-Swedish multinational pharmaceutical company AstraZeneca, the vaccine developer that has engaged in the most technology transfer and built the widest global manufacturing network, and Bio-Manguinhos, a public laboratory linked to Brazil’s Ministry of Health. The case study demonstrates the importance of capabilities and regulatory flexibility. Moreover, the analysis highlights the role of political factors that affect the process of technology transfer, and innovation more broadly. Because of the risks involved and the need to quickly mobilize existing capabilities and build new ones, as well as the imperatives of coordinating among manufacturing and regulatory processes and allocating resources to make such arrangements feasible, technology transfer projects need to be enabled politically. Looking forward, the case study has implications for initiatives to expand technology transfer for broadened production of vaccines in the Global South

Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.

Notch is a key player in various developmental processes during the embryonic stage as well as in regulating tissue homeostasis, cell differentiation, and stem cell maintenance in adult life. Activation of Notch signaling occurs following Notch receptor-ligand interaction and subsequent enzymatic proteolysis by the gamma-secretase complex, resulting in the cytoplasmic release of a Notch intracellular domain, which translocates to the nucleus to initiate the downstream transcriptional machinery. Notch activation and its aberrant signaling have been broadly linked to the pathogenesis of cancer and some chronic inflammatory diseases resulting in pathologic fibrotic processes. This review focuses on the molecular basis of Notch-induced signaling and its interaction with other pathways to identify therapeutic targets. We also highlight current efforts to pharmacologically intervene in Notch signaling and discuss promising ongoing experimental and clinical studies

Identification of IMDC intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma (ccRCC).

e16577Background: Majority of patients (pts) with ccRCC at first line (1L) treatment are classified in the IR subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium..

Safety and clinical activity of the Notch inhibitor, crenigacestat (LY3039478), in an open-label phase I trial expansion cohort of advanced or metastatic adenoid cystic carcinoma

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Methods Patients with advanced or metastatic cancer, measurable disease, ECOG-PS ≤1, and baseline tumor tissue were enrolled. Primary objectives were to identify a safe RP2D, confirm this dose in expansion cohorts, and document anti-tumor activity. Secondary objectives included safety and progression-free survival (PFS). The ACC expansion cohort received the RP2D regimen of 50 mg crenigacestat thrice per week in a 28-day cycle until disease progression or other discontinuation criteria were met. Results Twenty-two patients with ACC were enrolled in the expansion cohort (median age of 60 years). Median treatment duration was 3 cycles with 6 patients remaining on treatment. There were no objective responses; 1 (5%) patient had an unconfirmed partial response. Disease control rate was 73% and 4 patients had stable disease ≥6 months. Median PFS was 5.3 months (95%CI: 2.4-NE)) for the 22 patients; and 7.7 months (95%CI: 4.0-NR) and 2.4 months (95%CI: 1.1-NE) in the subgroup of patients in second-line (n = 7) or ≥ third-line (n = 9), respectively. Frequent treatment-related-adverse events (all grades) included diarrhea, fatigue, vomiting, decreased appetite, dry mouth, and dry skin. There were no new safety signals. Conclusion The crenigacestat RP2D regimen induced manageable toxicity and limited clinical activity, without confirmed responses, in heavily pretreated patients with ACC