The Newcastle upon Tyne Hospitals NHS Foundation Trust

The Newcastle upon Tyne Hospitals NHS Foundation Trust recently published, “Clinical trial hopes to predict response to cancer treatment”, which highlights iPREDICT clinical trial and CD8 ImmunoPET ™. Read what Dr. Rachel Pearson from the Northern Center for Cancer Care says about cancer research and for the first time hear from patient, Robert Charlton’s and his experience as a participant in the iPREDICT clinical trial. Clinical trial hopes to predict response to cancer treatment

Pictured: Sign at Pfizer’s world headquarters in New York iStock , JHVEPhoto Pfizer’s investigational Duchenne muscular dystrophy gene therapy, fordadistrogene movaparvovec, failed in a late-stage study to significantly improve motor function in patients versus placebo. Pfizer on Wednesday announced that its investigational Duchenne muscular dystrophy gene therapy, fordadistrogene movaparvovec, fell short of its primary efficacy endpoint in the Phase III CIFFREO study. The company did not provide specific data in its announcement, only revealing that the gene therapy candidate was unable to significantly improve motor function in boys aged four to seven years, compared to placebo. Fordadistrogene movaparvovec also failed key secondary endpoints, including 10-meter run/walk velocity and time to rise from floor velocity. Despite showing no significant signals of efficacy, fordadistrogene movaparvovec had a manageable safety profile, with most adverse events being mild to moderate in severity. Treatment-related serious toxicities generally responded to management. Dan Levy, development head for Duchenne muscular dystrophy (DMD) at Pfizer, said in a statement that the company is “extremely disappointed” by the results. “We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings” to help improve future research on DMD and develop effective treatment options for the disease, Levy said. Pfizer will continue to monitor study participants while it evaluates the next best steps for fordadistrogene movaparvovec, according to the announcement. Mainly afflicting young boys between two and three years of age, DMD is a severe genetic disorder that involves progressive muscular degeneration. The disease typically manifests initially as weakness and difficulties moving, before eventually affecting vital organs and leading to various complications, such as respiratory failure. DMD is caused by mutations to the gene encoding for the dystrophin protein, which is important for the stability and function of muscles. Fordadistrogene movaparvovec addresses the underlying cause of DMD by delivering a shortened but functional copy of the dystrophin gene. The candidate uses an AAV9 capsid delivery mechanism to specifically target muscle tissue. In addition to CIFFREO, Pfizer is assessing fordadistrogene movaparvovec in a Phase II DMD study. In May 2024, the pharma announced that a patient in the study “passed away suddenly” but did not provide the cause of death. In December 2021, Pfizer reported another patient death associated with fordadistrogene movaparvovec, which led the pharma to pause screening and dosing in its Phase Ib study. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

The accelerating discovery: actionable NASH cirrhosis endpoints (ADVANCE) study will be the most detailed observational study of its kind enrolling the largest number of patients and will provide a detailed analysis of liver health, those involved say. Nonalcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH) is an inflammatory liver disease caused by an accumulation of fat in the liver. There are approximately 444 million people worldwide living with the condition. The study will not only enhance the understanding of NASH cirrhosis but also help to identify translational biomarkers that will accelerate the development of future therapies. The formation of scar tissue on the liver, which can happen over time with NASH, can lead to cirrhosis which in turn can result in serious complications including liver failure or liver cancer, and may result in the need for a transplant. No approved cirrhosis medicines There are no approved medicines for cirrhosis so there is an urgent need for earlier diagnosis and new medicines to prevent MASH cirrhosis progression to liver failure, or to reverse the scarring of the liver once cirrhosis is established. Lykke Hinsch Gylvin chief medical officer at Boehringer Ingelheim, told Outsourding Pharma that cardiovascular, renal, and metabolic diseases are the leading cause of death worldwide, accounting for up to 20 million deaths annually. She said: “We are focusing on understanding the whole patient and how to target specific disease mechanisms to address interconnected CRM diseases. We are very excited to work with our partners in the ADVANCE study to better understand the underlying disease processes and to bring much-needed new treatments to patients with liver cirrhosis.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); Boehringer Ingelheim says funding the study reflects the company’s commitment to improving the lives of people living with cardiovascular, renal, and metabolic diseases (CRM). It will be led by researchers at Newcastle University and the University of Edinburgh, along with collaborators across Europe. Disease processes driving cirrhosis Professor Quentin Anstee is a professor of experimental hepatology at Newcastle University and consultant hepatologist at Newcastle Hospitals NHS Foundation Trust who is coordinating the global study. He said: “Building on Newcastle’s internationally recognized expertise in translational liver research, this study will reveal the fundamental disease processes driving cirrhosis. “We aim to work out why, even at the most advanced stages of liver disease, there is substantial variation in how the disease progresses with some people remaining well for many years whilst others rapidly experience liver failure or develop liver cancer. Working internationally with our collaborators, we will then use this knowledge to improve how patients are diagnosed, and to help develop new medicines.” Neil Henderson is professor of tissue repair and regeneration at the University of Edinburgh and co-lead on the study and his team is being supported by Edinburgh Innovations, the university's commercialization service. He said: “Liver disease has reached epidemic proportions worldwide. Therefore, there is a huge need to develop potent, new treatments for liver scarring. To help address this, over the last several years we have harnessed a new technology in Edinburgh called single-cell RNA sequencing. Using this new technology has allowed us to study human liver scarring in high definition for the first time, and we hope that this state-of-the-art approach will allow us to accelerate the discovery of much-needed new treatments for patients with liver disease.” Specialist liver clinics The study will include 200 patients with cirrhosis. Participating patients will be recruited at specialist liver clinics at hospitals across the UK and Europe or through referral by their treating physician. Participants will initially undergo a biopsy to collect a small sample of liver tissue so that detailed changes in gene expression in the liver can be assessed using advanced scientific techniques. They will then have blood tests and state-of-the-art MRI scans performed at regular time points over the next two years. The data generated will be combined to allow researchers to see how disease-related changes evolve in the body as cirrhosis progresses.