Phase 2b clinical trial planned after earlier results showed lung function gains by Lindsey Shapiro, PhD | September 24, 2024 FT011, Certa Therapeutics’ oral treatment candidate for systemic sclerosis (SSc), will now be known under the generic name asengeprast.
That decision was made by the World Health Organization (WHO), which is responsible for assigning International Non-Proprietary Names, or INNs, to pharmaceutical substances or active ingredients. INNs are globally recognized, unique identifiers for such substances, and may be understood as the generic name for an active ingredient in a medication. INNs are public property and aren’t owned by any particular company. “The granting of an INN for our lead drug candidate asengeprast is another important step in [the] development of this important therapy,” Darren Kelly, PhD, CEO, founder, and managing director of Certa, said in a company press release. “We are continuing to drive the clinical development of asengeprast and believe it has the potential to address a critical need for people living with SSc, a debilitating condition with the highest mortality amongst rheumatic diseases.” Kelly is also a professor at the University of Melbourne in Australia. The company plans to launch a confirmatory Phase 2b clinical trial with SSc patients after positive data from a Phase 2a clinical trial (NCT04647890) showed the treatment eased disease severity and improved lung function. It’s also working to develop biomarkers and gene signatures for identifying patients most likely to respond to the treatment. In SSc, the immune system launches harmful self-reactive attacks that cause fibrosis, or excessive scarring of the skin and internal organs. Outcomes differ for patients of different races, meaning antibodies play a role by Marisa Wexler, MS | September 17, 2024 Some types of disease-specific antibodies are more common in Black patients with scleroderma than white patients, a study shows.
Differences in antibody profiles may help explain why clinical outcomes tend to differ for patients of different races, but the data suggest these variations can’t fully account for all the clinical differences between races, meaning other factors must also factor in. “Distinct autoantibody types are enriched in Black [scleroderma] patients compared with those observed in white patients; these specificities associate with more aggressive clinical manifestations of the disease. However, differences in autoantibody distributions explain only a fraction of the racial effects on clinical outcomes,” the researchers wrote. The study, “Racial variability in immune responses only partially explains differential systemic sclerosis disease severity,” was published in the Annals of the Rheumatic Diseases. Scleroderma, also called systemic sclerosis, or SSc, is marked by uncontrolled fibrosis (scarring) that can affect various organs. Several specific types of autoantibodies, that is, antibodies that attack healthy tissue and are thought to be a main driver of the disease, have been linked to the disease. The biological consequences of individual autoantibody types are poorly understood, however. Calcium channel blocker seen to ease SSc symptoms such as Raynaud's by Margarida Maia, PhD | September 10, 2024 The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Aisa Pharma’s Profervia (cilnidipine), an investigational oral calcium channel blocker also known as AISA-021, for the treatment of systemic sclerosis (SSc).
In its request package for the designation, the company included data from an ongoing Phase 2 clinical study called RECONNOITER (ACTRN12621000459820) in which Profervia is showing benefits in easing symptoms of SSc. Among the symptoms reduced is Raynaud’s phenomenon, which causes pain and tingling in the hands and fingers. “We hope this designation will accelerate our development program for AISA-021, which is designed to provide a once-daily, well-tolerated, and economical treatment that we hope can improve the lives of patients with SSc,” Andrew Sternlicht, MD, Aisa’s CEO and founder, said in a company press release. The granting of orphan drug status provides an incentive for companies to develop products for rare diseases. The designation’s benefits include tax credits and a potential seven years of market exclusivity should the treatment ultimately be approved. According to Sternlicht, the company believes this is “the first time” a calcium channel blocker has been granted such a designation for an autoimmune disease. Early treatment could benefit at-risk patients, researchers say by Margarida Maia, PhD | August 20, 2024 Long-term treatment with Volibris (ambrisentan), marketed as Letairis in the U.S., may help prevent mild pulmonary vascular disease from developing into pulmonary arterial hypertension (PAH) in people with scleroderma, a study suggested.
“Early treatment and close follow-up could be beneficial in this high-risk group,” wrote the researchers from Germany and the U.K., who collaborated on the EDITA Phase 2 study (NCT02290613) and its long-term follow-up, EDITA-ON. The study, “Effect of ambrisentan in patients with systemic sclerosis and mild pulmonary arterial hypertension: long-term follow-up data from EDITA study,” was published in Arthritis Research & Therapy. Scleroderma, or systemic sclerosis, occurs when the immune system attacks the body’s own healthy tissues, and potentially affects the lungs. This can cause complications such as pulmonary vascular disease, a term for any disease that affects the blood vessels leading to or branching from the lungs. Patients with pulmonary vascular disease are at risk of developing PAH, which causes high blood pressure in the blood vessels taking blood from the heart to the lungs, making physical activity more difficult. Therapy particularly effective as add-on treatment by Patricia Inácio, PhD | August 13, 2024 Intravenous immunoglobulin (IVIG) eases skin, muscle and digestive symptoms in people with scleroderma (SSc), particularly when used as an add-on therapy, according to a recent review study.
While no improvements were seen in respiratory function, IVIG still led to stabilization of these symptoms. The findings “suggest that IVIG may be effective in treating a range of organ-specific manifestations with minimal side effects, thus making it a potentially attractive therapeutic option for SSc,” the researchers wrote. The review, “Role of intravenous immunoglobulins in systemic sclerosis (SSc): A systematic literature review,” was published in Seminars in Arthritis and Rheumatism. Scleroderma, also called systemic sclerosis, is an autoimmune disease that causes the hardening and fibrosis — thickening or scarring — of the skin. Often, scleroderma also affects internal organs, posing a risk of more severe outcomes. 25% of patients saw side effects months after treatment by Patricia Inácio, PhD | August 6, 2024 Scleroderma patients who have cancer may be treated with radiotherapy without a notable risk of skin and pulmonary worsening, a review study suggests, but around 25% of patients saw severe acute and late toxicities, that is, side effects months after radiation therapy.
As such, “individualized assessment, close collaboration between radiation oncologists and rheumatologists, use of high precision radiotherapy techniques to minimize dose to organs at risk, and vigilant monitoring are key to optimizing the risk-benefit balance,” scientists wrote in the review, “Effects of Radiotherapy for Malignancy in Systemic Sclerosis. A Systematic Review,” in The Journal of Rheumatology. Studies have shown that having scleroderma increases the risk for developing cancer, especially lung, blood and head and neck cancers. While radiotherapy is a cornerstone of cancer treatment, its use in scleroderma patients has raised concerns about causing severe skin thickening and localized scleroderma in people without prior disease. In fact, the American College of Radiology considers scleroderma and related disorders as contraindications for treatment to remove an area of cancer from the breast. Evidence in scleroderma is scarce, however, leading researchers from Canada and Saudi Arabia to review 26 studies published across four databases to better understand safety and outcomes of radiotherapy in scleroderma. Half the studies analyzed were case reports and most were from the U.S. The studies were published between 1987 and 2021, and taken together they reported on 121 scleroderma patients treated with radiotherapy. The patients’ mean age was 56.4 and 83.3% were female. Analysis IDs over 1,000 genes with different expression vs. controls by Patricia Inácio, PhD | July 30, 2024 Cells present along the walls of small blood vessels in the lungs, called pericytes, have distinct gene activity in people with systemic sclerosis (SSc)-associated pulmonary fibrosis (PF), according to a new study.
Pericytes from SSc patients showed an increased expression, or activity, of genes involved in lung fibrosis (scarring), blood vessel formation, and extracellular matrix organization. The extracellular matrix is a network of molecules that maintain cell structure. The study, “Transcriptomic characterization of lung pericytes in systemic sclerosis-associated pulmonary fibrosis,” was published in the journal iScience. Pulmonary fibrosis is a type of interstitial lung disease, a group of disorders marked by inflammation and fibrosis. SSc-associated PF is the leading cause of death in SSc patients. Pericytes are key cells for the maintenance of blood vessels in the lungs. These cells establish communication routes with other cells types, via a direct interaction or the release of growth factors. However, the role of pericytes in SSc-PF is still far from understood. Studies have suggested that they may contribute to the transition of fibroblasts into myofibroblasts, a normal process in wound healing. However, the persistent presence of myofibroblasts is key in driving tissue fibrosis. Designation grants developer 7 years market exclusivity if therapy is approved by Patricia Inácio, PhD | July 23, 2024 The European Medicines Agency (EMA) has granted orphan drug status to FT011, an oral therapy candidate that Certa Therapeutics is developing for systemic sclerosis (SSc).
The U.S. Food and Drug Administration (FDA) awarded the therapy a similar status last year, followed by fast track designation this year. Orphan drug status is given by both agencies to medicines designed for the treatment of serious or life-threatening rare diseases — those affecting fewer than five in 10,000 people in the European Union or fewer than 200,000 individuals in the U.S. Among its benefits is a period of marketing exclusivity should the therapy be approved; that period is seven years in the U.S. and 10 years in Europe. “With limited treatment options available for patients with SSc, the EMA orphan drug designation and FDA orphan drug and fast track designations reflect the potential for FT011 to address a critical need for people living with this debilitating and life-threatening condition,” Darren Kelly, PhD, founder and CEO of Certa, said in a company press release. “These are significant validations for the company and highlight the unmet need for novel medicines to reduce inflammation and scarring in chronic fibrotic diseases, which are often progressive and can have a poor prognosis,” Kelly added. SCOT trial studied potential benefits over high-dose Cytoxan by Andrea Lobo, PhD | July 16, 2024 Patients with systemic sclerosis (SSc) who have a stem cell transplant see normalized gene activity related to immune function up to 4.5 years after the procedure.
That’s according to recent data from samples in the Phase 2/3 SCOT trial (NCT00114530), wherein the potential benefits of a stem cell transplant were compared with those of high-dose Cytoxan (cyclophosphamide) in severe SSc. “The normalization of the SSc [molecular] signature … parallels the clinical benefits of [stem cell transplant] at this time point and provides support for these disease-related pathways as therapeutic targets,” the researchers wrote in “Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long-Term Normalization of Systemic Sclerosis Molecular Signatures,” which was published in Arthritis & Rheumatology. SSc, or scleroderma, is an autoimmune disease where scar tissue (fibrosis) accumulates in the skin and possibly in the organs, such as the lungs, heart, or kidneys. Transplanting hematopoietic stem cells (HSC), which are precursors to all types of blood cells, has been investigated as a way to reset the immune system in people with SSc. Ferroptosis, natural block on uncontrolled cell growth, seen to be suppressed by Lindsey Shapiro, PhD | July 9, 2024 Ferroptosis, a cell death process that can help to regulate uncontrolled cell growth, was suppressed in skin cells from people with systemic sclerosis (SSc), according to recent research.
Such suppression appears to be mediated by increased activity of an antioxidant protein called GPX4. Researchers believe that targeting GPX4 to increase ferroptosis could offer a way of preventing the uncontrolled cell growth that drives scar tissue buildup, or fibrosis, in the skin of SSc patients. The study, “Upregulation of GPX4 drives ferroptosis resistance in scleroderma skin fibroblasts,” was published in Free Radical Biology and Medicine. Skin fibrosis in SSc tied to excess of fibroblasts and collagen SSc, also known as scleroderma, is an autoimmune disease wherein scar tissue accumulates in the skin and, in another disease type, in internal organs as well. Skin fibrosis is caused by the rapid and uncontrolled growth, or proliferation, of cells called fibroblasts and excessive production of collagen, a connective tissue protein. However, it is not clear what initially drives these processes, and current disease treatments aim to manage symptoms associated with scleroderma. No available therapies are specifically designed to target fibrosis in SSc, the study’s researchers stated. Programmed cell death refers to types of cell death that occur naturally and serve important biological functions. Ferroptosis is one form of programmed cell death that’s believed to help prevent the excessive cell growth that characterizes cancer. In ferroptosis, iron triggers the overproduction of toxic reactive oxygen species (ROS) molecules. This leads to a state of oxidative stress, an imbalance between ROS and the antioxidant molecules that counterbalance them, which ultimately drives cell death. As such, antioxidants can regulate ferroptosis. This form of programmed cell death has been identified as a possible therapeutic target in SSc, but the exact relationship remains to be thoroughly investigated. |
AuthorScleroderma Queensland Support Group Archives
September 2024
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