Aortopulmonary Septal Defect

CARLSBAD, Calif., Feb. 15, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to the investigational medicine olezarsen for the treatment of familial chylomicronemia syndrome (FCS), a rare, genetic disease characterized by extremely elevated triglyceride levels and recurrent acute pancreatitis (AP). The FDA grants Orphan Drug designation to therapies intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation. "People living with FCS are in urgent need of a medicine that may help stabilize their triglyceride levels and reduce the risk of life-threatening AP attacks," said Sam Tsimikas, M.D., senior vice president, global cardiovascular development of Ionis. "If approved, olezarsen has the potential to be the standard of care in the U.S. for the treatment of FCS. We are deeply committed to advancing this important medicine that has the potential to be transformative for people and families living with FCS." FCS prevents the body from breaking down fats, which can result in fasting triglyceride levels that can range from 10 to 100 times higher than normal levels.1,2 People with FCS are at high risk of AP, or inflammation of the pancreas, which often results in hospitalization and can be life-threatening.3 In severe cases, vital organs such as the heart, lungs, kidneys and pancreas can be damaged.4 Under the FDA's Orphan Drug Act, orphan drug status provides incentives, including tax credits, grants and waiver of certain administrative fees for clinical trials, and seven years of market exclusivity following drug approval. About Olezarsen Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials. About FCS FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact one to two people per million worldwide. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and standard triglyceride lowering therapies are generally ineffective in patients with FCS. People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to adhere to diets to navigate the health risks associated with FCS. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Forward-looking Statements This press release includes forward-looking statements regarding olezarsen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2022, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. 1 Pallazola et al. Eur J Preventive Cardiol 2020 27:2276-2278. 2 Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. 3 Chyzhyk V, Brown AS. Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis. Trends Cardiovasc Med. 2020;30(2):80-5. 4 "Pancreatitis." WebMD. . SOURCE Ionis Pharmaceuticals, Inc.

Peca Labs , a medical device company making vascular grafts and valves with durable polymeric cardiovascular devices designed to fit, grow, and last in pediatric populations, recently announced its first successful in-human implant of the Masa valve. The valve is intended to be used to reconstruct the right ventricular outflow tract (RVOT) and provide a functional pulmonary valve in patients up to age 22. Once implanted, Masa provides a pathway for blood from the right ventricle to the pulmonary arteries, using its design to help prevent backflow into the right ventricle. The valve is a bi-leaflet pulmonary valved conduit . It has an expanded polytetrafluoroethylene (ePTFE) conduit and ePTFE leaflets fixtured to the conduit with polypropylene suture. The device includes a pad-printed design on the outer surface to indicate valve position and direction of flow. Image courtesy of Peca Labs Peca has received Humanitarian Use Device (HUD) and Investigational Device Exemption (IDE) designation from FDA and has begun enrollment for its Masa Valve Early Feasibility Clinical Study at four clinical sites in the United States. One of the study sites included is Children’s Hospital of Philadelphia, which is where the successful first in-human implant recently took place. The valve was reportedly implanted in a 21-month-old child who had previously undergone surgery for a homograft at one year old. The homograft, also known as a human tissue valve, had become severely stenotic and required immediate replacement. In turn, the homograft has been replaced with a 14mm Masa valve and the patient has shown encouraging early results post-procedure, with promising valve functionality on early assessment, according to the company. "This successful implant marks a historic step for our polymeric valve technology that aims to combine the bio-inert benefits of organic tissue and durability of mechanical valves to potentially reduce the need for additional surgeries. The Masa valve materials and design may also help to preserve native tissue that would otherwise be used for a part of the reconstruction and could reduce the amount of medication needed for the patient during their lifetime," Arush Kalra, chief scientific officer and co-founder at Peca Labs, wrote in a statement for MD+DI . "This case brings Masa valve one step closer to being available to children who need such transformational innovation the most, furthering Peca's goal to save and improve lives." Other existing valve implants are made with metal, ceramic or bioprosthetic materials, which can “cause biological responses, lack customizability, cannot be grown, and are destined to fail within five to 10 years,” according to a press release announcing the in-human implant. “Failed conduits require repeat surgeries and interventions, costing more than $100,000 per patient on average, and current interventions for failed implants don’t resolve the core reason for failure.” The Masa valve is named after its inventor, Masahiro Yoshida, MD, PhD , who created the concept after observing issues using biologic valve replacements including calcification, limitations of valve expansion on a growing heart, and shorter times between surgical replacements. Pediatric patients born with valve defects related to a number of congenital heart conditions — pulmonary stenosis, tetralogy of fallot, truncus arteriosus, transposition of great vessels, and pulmonary atresia — require multiple open-heart surgeries from childhood to adulthood. Especially in very young patients, implanted valves and conduits need to be replaced with larger ones as the heart grows. Yoshida, in turn, designed a PTFE implant that was more adaptable to a growing heart, reduced the issues of calcification, and expanded the intervals between replacements. It was years later that three Carnegie Mellon University students formed Peca as a startup near Pittsburgh to commercialize a product based on Dr. Yoshida’s concepts, creating the Masa valve. The company developed the valve to be made entirely out of polymeric materials to help avoid some of the complications that come with the use of biologic valves. Masa does not use biologic or foreign tissue, meaning that the body will not have any immune response to the device. Additionally, its polymeric material helps avoid valve calcification and can be produced in an array of sizes to match each patient’s anatomy. “In designing the Masa valve, we aimed to use our polymer platform to combine the best characteristics of homograft tissue, which reduces the antithrombotic therapy required, and mechanical valves, which offer improved durability, supply availability, and resistance to both calcification and shrinkage,” said Doug Bernstein, CEO at Peca Labs. “We then improved upon them with a novel bi-leaflet design.” Now embarking on the enrollment stage of its clinical study, the company is slated to enroll 10 to 15 patients at up to five sites. The study, which is multi-center, non-randomized, prospective, and interventional, is set to determine the safety and probable benefit of Masa by following implanted subjects for a total of five years post-procedure with a post-op, 30-day, 180-day, and one year follow-up, followed by an annual follow up until five years.