NPRA

Idorsia plans to launch the hypertension therapy Tryvio in the US in H2 2024. Image Credit: JHVEPhoto / Shutterstock. Switzerland-based Idorsia has received approval from the US Food and Drug Administration (FDA) for the use of Tryvio (aprocitentan) as a combination treatment for hypertension in patients whose blood pressure is inadequately controlled with other antihypertensive drugs. The news comes a few months after the company signed a deal with Johnson & Johnson to reacquire global rights for Tryvio . Idorsia agreed to pay up to Sfr306m ($343.5m) contingent on the EU and US approvals of the drug. Tryvio is an endothelin receptor antagonist, which inhibits the binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells which results in vasodilation, ultimately, leading to a reduction in blood pressure. Idorsia plans to launch Tryvio in the US in H2 2024. The approval was based on the Phase II and Phase III trial data. Tryvio showed a reduction in blood pressure for up to 48 weeks in the Phase III PRECISION trial (NCT03541174). One of the main side effects of the drug was fluid retention, which can cause rapid weight gain and stiffness of joints. The global market for resistant hypertension is expected to be worth $895m by 2030, according to a GlobalData market analysis . The main competitor for Tryvio for this indication is expected to be AstraZeneca ’s baxdrostat. While Tryvio will have the first-to-market advantage, baxdrostat is expected to generate $506m in sales in 2030, compared to $141m estimated for Tryvio during the same period. See Also: Donanemab: FDA AdCom will put spotlight on tau enrolment and ARIA concerns GlobalData is the parent company of Pharmaceutical Technology . AstraZeneca added baxdrostat to its portfolio as part of the $1.8bn acquisition of CinCor Pharma in January 2023. Baxdrostat is a selective aldosterone synthase inhibitor. The drug is being evaluated in a Phase III BaxHTN trial (NCT06034743). The study is expected to enrol up to 720 participants with resistant hypertension taking two or more hypertensives to control their blood pressure. Another drug in development for treating resistant hypertension is Novartis ’ XXB750, a natriuretic peptide receptor 1 (NPR1) agonist. The drug is being evaluated in a Phase II trial (NCT06034743). The study is expected to enrol up to 170 participants and will be completed in September 2024.

Researchers have pinpointed a particular peptide's role in activating atopic dermatitis, or eczema. The work could lead to more effective treatments for the condition. Researchers from North Carolina State University have pinpointed a particular peptide's role in activating atopic dermatitis, or eczema. The work could lead to more effective treatments for the condition. Atopic dermatitis (AD) is a skin condition characterized by itching, irritated and thickened skin at the site of the irritation. The brain natriuretic peptide (BNP) is a peptide, or short chain of amino acids, that is elevated in patients with AD. "BNP is expressed in sensory neurons, the neurons responsible for conveying sensation to the brain via the spinal cord," says Santosh Mishra, associate professor of molecular biomedical sciences at NC State and corresponding author of the work. "We know from previous work that BNP helps translate the sensation of itch from the skin to the brain. In this work we wanted to see if BNP was involved in activating AD." In a chemically induced mouse model of AD, the researchers saw that mice without BNP did not exhibit the thickened or irritated skin commonly associated with AD, and their itching was reduced compared with control mice who did have BNP. "The results show that BNP likely plays a role in itch activation," Mishra says. "We next looked at BNP's relationship to periostin, to see if we could determine how that activation takes place." Periostin is a protein that can interact with sensory neurons in skin to activate itch response. It is produced in skin cells called keratinocytes and fibroblasts. Keratinocytes in turn, have receptors for BNP, which are called NPR1 receptors. When the BNP receptors are activated, periostin is produced and itch can be turned on. "But the interesting thing here is that the sensory neurons are the activator," Mishra says. The neuron releases BNP, which activates keratinocytes with the NPR1 receptor, which then release the periostin. "This work shows that peripheral neurons, not just central neurons, are playing a role in AD -- it begins in the sensory neurons, and cascades from there," Mishra adds. "It also points to some potential therapeutic strategies, such as blocking BNP's ability to bind to NPR1 receptors in the skin." The research appears as a letter to the editor in the Oct. 11 issue of the Journal of Investigative Dermatology. The work was supported by the National Institutes of Health under grant number 1R56AR077692-01. NC State undergraduate student Junho Yu, former NC State undergraduate student Nidha Williams, and NC State postdoctoral research scholar Joshua Wheeler, also contributed to the work.

Akosua Mireku @AkosuaMireku1 Under Section 505 of the Cures Act, the FDA was mandated to create a framework on how real-world evidence and data could be used in the drug evaluation process. Credit: Bet_Noire via Getty Images. The US Food and Drug Administration (FDA) has released a final draft guidance detailing how pharmaceutical companies should use real-world evidence to support the regulatory review process for new therapies. The FDA defines real-world data as “data relating to patient health status and/or the delivery of healthcare routinely collected from a variety of sources” and real-world evidence as “the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of real-world data ”. Recommended Reports Reports Atrial Natriuretic Peptide Receptor 1 (Atrial Natriuretic Peptide Receptor Type A or Guanylate Cy... GlobalData Reports Platelet Derived Growth Factor Receptor (PDGFR or EC 2.7.10.1) Drugs in Development by Therapy Ar... GlobalData View all The new draft guidance is designed as per stipulations in the 21st Century Cures Act (Cures Act). Enacted in 2016, the legislation is meant to boost medical product development and give patients quicker access to health innovations. Under Section 505 of the Cures Act, the FDA was mandated to create a framework on how real-world evidence and data could be used in the drug evaluation process. Since the Act’s conception, the FDA has increasingly accepted the use of real-world evidence and data for the approvals of different drugs . In addition, real-world data has become a more popular way for sponsors to conduct Phase IV studies, above other phases, according to GlobalData . GlobalData is the parent company of Pharmaceutical Technology. The FDA stated that it would be open to receiving evidence from “non-interventional studies, including registries, electronic health records (EHRs), and medical claims”, without the need for an investigational new drug (IND) application. However, the guidance highlighted that drug manufacturers using non-interventional studies to support a marketing application should engage with the agency early in the drug development process. This would be through an appropriate regulatory pathway such as arranging a type C meeting through an IND. In the document, the agency also acknowledged the benefits of the potential use of real-world data to support the safety and/or effectiveness of a drug. However, they asserted that if this data is obtained in non-interventional studies, it is important for sponsors to take responsibility for maintaining study records and allow FDA access to the records amongst other things. The guidance also recommended that sponsors come to an agreement with any external sources of real-world data to ensure that relevant patient-level data can be provided to the FDA. If this is not possible for a justifiable reason, the FDA would allow third parties to submit the data through a separate regulatory pathway. The recommendations made in the guidance are non-binding but represent the agency’s current thinking on the topic.