The Children's Mercy Hospital

Arimoclomol was originally submitted to the FDA in July 2020 but was rejected almost a year later because the agency questioned aspects of the single clinical trial used to support the application. Zevra Therapeutics’ rare disease drug seems to be on the path to approval this fall after gaining the backing of an FDA advisory committee, although the experts were split, with some voting yes simply to address an unmet need.The agency’s Genetic Metabolic Diseases Advisory Committee voted 11 to 5 in favor of arimoclomol on a questions of whether the evidence supports the drug’s efficacy to treat patients with Niemann-Pick disease type C at the Friday meeting. The rare, genetic lysosomal storage disease prevents the body from moving and using cholesterol and other lipids in cells. This leads to a build-up of cholesterol and other lipids in the liver, spleen or lungs.There are no approved treatments for the disease, according to the FDA. Patients typically receive anti-seizure medicine and other supportive care.The FDA is set to decide on the drug’s approval by September 21. While the agency does not have to do exactly as the committee suggested, it does typically heed the advice of its expert panels.Arimoclomol was originally submitted to the FDA in July 2020 but was rejected almost a year later because the agency questioned aspects of the single clinical trial used to support the application. While the FDA can approve a drug based on evidence from just one trial, the applicant must show that the test meets the bar of being considered a “single adequate and well-controlled clinical trial.”Zevra submitted data from a 12-month, randomized double-blind, placebo-controlled study called CT-ORZYNPC-002. The main goal was a measure of disease severity called the 5-domain NPC Clinical Severity Scale (5DNPCCSS), which assesses clinical outcomes for the disease, including swallowing, speech, fine motor, ambulatory, and cognitive functioning. In the complete response letter from 2021, the FDA questioned the interpretability of the 5DNPCCSS, specifically its validity and reliability. There were also concerns with the prespecified primary analysis of the 5DNPCCSS endpoint and lack of statistical significance in the FDA’s own post hoc analyses of the 5DNPCCSS endpoint. And finally, the agency flagged “weak and contradictory confirmatory evidence of effectiveness,” specifically inconsistent results in mouse studies.Zevra was asked to address the swallow scores and whether a rescoring of the scale or alignment with a National Institutes of Health measure of swallowing would be better. The company was also directed to produce more evidence to support the interpretation and use of the 5DNPCCSS score, check whether evidence from the existing clinical trial would be good enough to support a re-application and “bolster the confirmatory evidence.”With that long to-do list, Zevra returned to the FDA in December 2023 with a rescored scale and more results from the study, including data from an open-label expansion phase. Zevra also submitted a natural history comparison of the disease from the NIH and more preclinical evidence.At the advisory committee meeting, the FDA wanted the experts to consider the validity of the new four-point scale and the post-hoc exploratory revision of the primary efficacy endpoint. The committee was also tasked with considering the uncertainty of the estimated treatment effect on the revised primary endpoint; adequacy of the additional clinical and nonclinical evidence; and the strength of the overall evidence to support the efficacy of arimoclomol.After the vote, many of the panel members said they were torn on the efficacy package, but ultimately Zevra's therapy passed.  “I voted yes but it was a very reluctant yes. I found the effect size to be small and the strength of the data to be weak, but overall the bulk of the data favored a slightly positive effect,” said Jonathan Mink, M.D., Ph.D., a private consultant. “I think the unmet need is very clear. I’m not sure this meets that need, but again on balance I voted yes.”Priya Kishnani, M.D., also voted yes, noting the clinical unmet need, very good safety profile and trends toward efficacy. Kishnani is a professor of pediatrics at the Duke University Medical Center. Jean Baptiste Le Pichon, M.D., Ph.D., voted yes as well, but said he did not rely on the nonclinical data that was submitted to make his decision. Le Pichon, a professor of pediatrics and the associate director for the Division of Neurology at Children's Mercy Kansas City and the University of Missouri Kansas City, said that the data were “not convincing.”When looking at the clinical data, however, Le Pichon was convinced that there was enough of an effect to recommend approval of arimoclomol.“It was not an enormous effect but it was an effect that was clinically significant,” Le Pichon said.He acknowledged that he may have broken the rules of the vote by ignoring the preclinical evidence. But the clinical data was what mattered the most to him.“If I was forced to vote no just because the non-clinical data was not convincing then I went against the rules but this is where my clinical intuition was and I am a clinical at heart,” Le Pichon said.Gerard Berry, M.D., professor of pediatrics at Harvard Medical School, voted yes, noting that the testimony of the families that arimoclomol led to a beneficial effect was moving.“Taking all data together it made sense that this is having a beneficial effect,” Berry said.Kenneth Fischbeck, M.D., who voted no, was not convinced that the new data helped the re-application, calling it “problematic.”“I think it could be done better. I think there’s a real unmet need in this space. And I think this drug or one like it could be effective but I haven’t seen the data yet to make a convincing case,” Fischbeck said in explaining his vote.Like Berry, Robert Alexander, M.D., was moved by the patient testimony, but said it was not enough to convince him that the trial showed benefit. He “had to rely on the data from the controlled trial and I didn’t feel like it really rose to the level of substantial evidence of efficacy on its own.” Alexander is the chief scientific officer for the Alzheimer’s Prevention Initiative at the Banner Alzheimer’s Institute and a research professor at the University of Arizona College of Medicine.

The collaboration will create enhanced and sustainable pediatric care close to home for the region SPRINGFIELD, Mo. , March 19, 2024 /PRNewswire/ -- After years of searching for a sustainable way to enhance pediatric care in southwest Missouri, Mercy is excited to announce plans to bring Children's Mercy Kansas City to town. "We have spent the last year looking at ways to elevate pediatric care across our region," said David Argueta, president of Mercy Southwest Missouri. "Because a significant number of our region's children have to travel to Kansas City or St. Louis to receive the specialized care they need, we knew we had to find a solution that would allow our kids to get care here at home as often as possible." According to market share data, 27% of patients leave the region for care. The plan to welcome Children's Mercy Kansas City to the Mercy Hospital campus comes after Mercy and CoxHealth announced in 2023 that they were teaming up with the intent of bringing a pediatric hospital to the area to provide enhanced pediatric care. After a request for proposal period, several hospitals were in the running, including Children's Mercy Kansas City. Unfortunately, Mercy and CoxHealth did not come to an agreed-upon path forward with a partner. "We knew there weren't many examples of what we were aiming to accomplish across the country and that there was a chance we wouldn't reach an agreement," Argueta said. "But we also know we need to enhance pediatric care in our region and make it locally available, so working alongside CoxHealth to evaluate options was the right place to start. I'm incredibly proud of our two teams for working together and making this issue a priority for our community, and while I'm disappointed we didn't come to an agreement, I am pleased that we have agreed to collaborate with Children's Mercy Kansas City to create an exceptional solution for the region that meets our primary objective, which is to provide care to our kids close to home." As part of the evaluation process, Mercy's leadership team visited several health care organizations during the past year, including Children's Mercy Kansas City. "From the first moment we set foot in their facility in Kansas City, it was clear that everything they do is about kids," said Marie Moore, chief nursing officer at Mercy Springfield Communities. "As an independent hospital, Children's Mercy Kansas City's sole focus is pediatric care. From the way they design their facilities, their commitment to world-class translational research, the way they engage families as true partners in the child's care, the amenities they offer, everything is done first with kids' needs in mind. They are set to bring that level of care to Springfield, and we are excited to welcome them, especially since so many in our community already utilize Children's Mercy Kansas City." To best gauge the community's preference for a world-class pediatric care provider, Mercy asked Monigle, a nationally recognized brand and consumer research firm, to independently survey 300 health care decision-makers in southwest Missouri. Consumers expressed a clear and statistically significant preference for Children's Mercy Kansas City as the pediatric hospital partner by a 17% margin compared to other pediatric hospitals in the region. The data also showed that Children's Mercy Kansas City had the highest awareness among pediatric hospitals surveyed, and 17% of the children in the area have received care from Children's Mercy Kansas City in contrast to 8% who have used St. Louis Children's and 2% who have used SSM Health Cardinal Glennon Children's Hospital, both in St. Louis. The independent data made clear that parents and health care consumers in this region want Children's Mercy Kansas City to be their kids care provider. "We are excited to collaborate with Mercy to increase pediatric services in the community to ensure families have access to world-class research and innovative care close to home," said Paul Kempinski, MS, FACHE, president and CEO, Children's Mercy Kansas City. "By creating a pediatric system of excellence in southwest Missouri, our patients will no longer need to drive several hours for appointments and care, which will help improve access and outcomes for all the children we serve in the area. Fundamentally, this is about providing excellent care to kids in their community." Children's Mercy Kansas City is one of only 30 centers in the nation to be verified as a Level 1 Children's Surgery Center. In addition, it is also a Level 1 pediatric trauma center and has the busiest critical care transport department in the country with 6,000 transports per year. When it comes to national awards, Children's Mercy Kansas City is continuously ranked as one of America's Best Children's Hospitals and ranked the No. 1 children's hospital in Missouri by U.S. News & World Report. Children's Mercy Kansas City earned its fifth consecutive Magnet award, making it the only hospital in Missouri to earn five Magnet designations. The American Nurses Credentialing Center's Magnet Recognition Program is nursing's highest honor, recognizing health care organizations that provide the best possible quality in nursing care. Children's Mercy's Research Institute is a world leader in pediatric genomics, personalized medicine, and other areas of emphasis that will bring advancements in care directly to the children of Springfield. "When we evaluated all of the providers that took part in the request for proposal, we were most impressed by Children's Mercy Kansas City," Moore said. "They have a long history of engaging with the community in shared decision-making, which we think makes them uniquely equipped to come to our community and provide care for our kids. They don't simply set up shop and open their doors. They collaborate with the community, and that's what we and parents across the region want for our kids." Mercy, one of the 20 largest U.S. health systems and named the top large system in the U.S. for excellent patient experience by NRC Health, serves millions annually with nationally recognized care and one of the nation's largest and highest performing Accountable Care Organizations in quality and cost. Mercy is a highly integrated, multi-state health care system including more than 50 acute care and specialty (heart, children's, orthopedic and rehab) hospitals, convenient and urgent care locations, imaging centers and pharmacies. Mercy has over 900 physician practice locations and outpatient facilities, more than 4,500 physicians and advanced practitioners and 50,000 co-workers serving patients and families across Arkansas, Kansas, Missouri and Oklahoma. Mercy also has clinics, outpatient services and outreach ministries in Arkansas, Louisiana, Mississippi and Texas. In fiscal year 2023 alone, Mercy provided more than half a billion dollars of free care and other community benefits, including traditional charity care and unreimbursed Medicaid. SOURCE Mercy

ORANGE, Calif., July 27, 2023 /PRNewswire/ -- Dr. William Adelman has joined Children's Hospital of Orange County (CHOC) as the new medical director of the CHOC Primary Care Network. He brings more than 20 years of experience in adolescent medicine to the role. Continue Reading Dr. William Adelman has joined Children’s Hospital of Orange County (CHOC) as the new medical director of the CHOC Primary Care Network. Most recently, Dr. Adelman served as the executive director, student health and counseling at the University of Pennsylvania, where he helped advance a transformative initiative to integrate physical and behavioral health services for more than 26,000 students. Previously, he was the director of adolescent medicine at Children's Mercy Hospital in Kansas City, Missouri. Prior to joining the public sector, he was the chief of adolescent and young adult medicine and chief of pediatric primary care services at Walter Reed National Military Medical Center; the deputy commander to clinical services at Kirk U.S. Army Health Clinic; and the adolescent medicine consultant to the U.S. Army Surgeon General. A published author on a variety of adolescent health topics, Dr. Adelman has served on numerous national committees dedicated to advancing the health and well-being of teens and young adults. He has earned numerous awards and is a retired U.S. Army Colonel. "We are thrilled to welcome Dr. Adelman to CHOC. His impressive experience in adolescent medicine, medical leadership and improvement science will help us continue to grow and enhance the pediatric and adolescent primary care services we provide across Southern California," said Dr Charles Golden, assistant chief medical officer, CHOC. Dr. Adelman received his medical degree from Tufts University and did his post-graduate training at the Walter Reed Army Medical Center and National Capital Consortium in Bethesda, Maryland. He completed his adolescent medicine fellowship at Johns Hopkins University. About CHOC: Children's Hospital of Orange County (CHOC), a nationally recognized pediatric healthcare system based in Orange County, California, is committed to being a leading destination for children's health by providing exceptional and innovative care. CHOC's community includes two state-of-the-art hospitals in Orange and Mission Viejo and a regional network of primary and specialty care clinics serving children and families across four counties. CHOC offers several clinical programs of excellence providing the highest levels of care for the most serious pediatric illnesses and injuries, physical and mental. CHOC's research and innovation institutes are focused on translating real patient needs into real-world treatments so every child can live the healthiest and happiest life possible. MEDIA CONTACT: [email protected] SOURCE CHOC