From Trials to Triumph: 2024’s FDA approvals

2024 was a year to remember, marked by elections, hurricanes, and the second-largest number of new FDA-approved medications since the 1990s. Last year, the FDA approved 50 new drugs for public use, and approved changes and improvements to a number of medications on the market. These approvals covered first-in-class treatments, improved treatments, and drugs that help diagnose diseases. ENCORE Research Group, a MedEvidence! affiliate company, was part of the multi-center clinical trial effort for five of those treatments.

Let’s start with the liver. One of the leading causes of liver transplant in 2024 was metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH). This is a progressive, multifactorial disease affecting around six percent of the US population. It is characterized by liver cell damage and inflammation, which results in scarring called fibrosis. One underlying problem in liver cells is the thyroid hormone receptor beta (THR-β), a cell receptor that malfunctions and disrupts the function of the cell’s powerhouse, the mitochondria. Madrigal Pharmaceutical’s Rezdiffra (resmetirom) was granted accelerated approval for use with diet and exercise on March 14th as a once-daily oral medication that targets THR-β to decrease liver scarring. This was a landmark medication and the first FDA-approved medication for moderate to advanced MASH/NASH. Clinical trials for Rezdiffra took place at Jacksonville Center for Clinical Research, Nature Coast Clinical Research - Inverness, and St Johns Center for Clinical Research.

Descending from the liver to the gut are bile ducts. These carry bile - an important digestive fluid - from the liver to the gallbladder on its way to the small intestine. Primary biliary cholangitis is a disease where the immune system mistakenly attacks and destroys the bile ducts, resulting in a dangerous buildup of bile in the liver which causes damage. This rare autoimmune liver disease has few effective treatments. Genfit/Ipsen received accelerated approval for Iqirvo (elafibranor) on June 10th. This first-in-class, once-daily oral medication acts on peroxisome proliferator activated receptors (PPARs), which work by reducing bile production, assisting the body in clearing cholesterol, and providing anti-inflammatory benefitss. Iqirvo clinical trials were conducted at ENCORE Borland Groover Clinical Research.

The kidneys are positioned behind and below the liver. They are essential blood filters for maintaining our health. With chronic kidney disease (CKD), one common issue is anemia, a condition where the body doesn’t have enough healthy red blood cells to deliver adequate oxygen. This complication of CKD is very serious and is usually treated by adding supplemental iron and other medicines, called erythropoiesis-stimulating agents, which regulate hemoglobin (a red blood cell protein) for patients on dialysis. These drugs can have adverse effects on the heart. Akebia Therapeutics received FDA approval for Vafseo (vadadustat) on March 27th, which uses a different therapy method. This once-daily oral tablet helps the body stabilize the concentration of proteins that detect and react to low oxygen in the blood, helping the body correct CKD-induced anemia itself. Clinical trials for Vafseo were performed at Jacksonville Center for Clinical Research and with ENCORE Research Group’s Hospital Team, which partnered with Dr. Ranjan at Baptist.

Descending further into the gut, we find the intestinal tract. Crohn’s disease is an inflammatory bowel disease causing painful inflammation along any portion of the gastrointestinal tract. This inflammation is caused by erroneous immune cells and particles entering healthy tissue. For patients who have not had success with conventional medications, Takeda Pharmaceutical’s Entyvio (vedolizumab) has been on the market as an IV treatment since 2014. This monoclonal antibody binds to specific receptors in the gut and interferes with the ability of immune cells to bind and enter gut cells, helping reduce inflammation. Entyvio was approved on April 18th as a reformulated liquid form that could be injected subcutaneously, like an epi-pen. This new delivery method should prove more manageable and less restrictive for people with Crohn’s disease. Trials at Nature Coast Clinical Research - Inverness helped show the safety and effectiveness of this new delivery system.

Finally, we shift our focus upward to the brain, the center of our personality (though a good chunk of mine might reside in the cookie-loving part of my GI tract). Alzheimer’s disease is devastating and all too common, affecting somewhere around 6 million adults over 65 in the U.S. It’s a progressive degenerative disease causing memory loss, cognitive decline, and behavior changes. Anatomically, the disease is characterized by misfolded proteins that accumulate in the brain, causing cell death. These proteins fall into two major categories: amyloid beta plaques between brain cells (neurons) and tau tangles within them. Lilly’s Kisunla (donanemab) received FDA approval on July 2nd to treat early symptomatic Alzheimer’s disease. Kisunla is a once-monthly IV infusion that targets amyloid beta and marks the proteins for clearance by the brain’s trash collectors. Jacksonville Center for Clinical Research helped with many clinical trials testing the effectiveness and safety of Kisunla.

2024 was an exciting year for clinical research and for the millions of patients who will benefit from the hard work, sacrifice, and effort of the participants, investigators, staff, and auxiliary media writers who made it all happen. You can be part of this medical legacy by joining a clinical trial in 2025!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

References

Akebia Therapeutics, Inc. (27 March, 2024). Akebia receives FDA approval of Vafseo® (vadadustat) tablets for the treatment of anemia due to chronic kidney disease in adult patients on dialysis. PR Newswire. [Website, accessed 13 January 2025]. https://www.prnewswire.com/news-releases/akebia-receives-fda-approval-of-vafseo-vadadustat-tablets-for-the-treatment-of-anemia-due-to-chronic-kidney-disease-in-adult-patients-on-dialysis-302101854.html

Chertow, G. M., Pergola, P. E., Farag, Y. M., Agarwal, R., Arnold, S., Bako, G., ... & Eckardt, K. U. (2021). Vadadustat in patients with anemia and non–dialysis-dependent CKD. New England Journal of Medicine, 384(17), 1589-1600. https://www.nejm.org/doi/full/10.1056/NEJMoa2035938

Harrison, S. A., Bedossa, P., Guy, C. D., Schattenberg, J. M., Loomba, R., Taub, R., ... & Ratziu, V. (2024). A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. New England Journal of Medicine, 390(6), 497-509. https://www.nejm.org/doi/full/10.1056/NEJMoa2309000

Ipsen. (10 June, 2024). Ipsen’s Iqirvo® receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitis. [Website, accessed 13 January, 2025]. https://www.ipsen.com/press-releases/iqirvo-elafibranor-data-shows-efficacy-and-safety-for-up-to-3-years-in-patients-with-pbc-with-improvements-in-fatigue-and-pruritus-2982128/

Jayaprakash, N., & Elumalai, K. (2024). Translational Medicine in Alzheimer's Disease: The Journey of Donanemab From Discovery to Clinical Application. Chronic Diseases and Translational Medicine.  https://onlinelibrary.wiley.com/doi/full/10.1002/cdt3.155

Kowdley, K. V., Bowlus, C. L., Levy, C., Akarca, U. S., Alvares-da-Silva, M. R., Andreone, P., ... & Schattenberg, J. M. (2024). Efficacy and safety of elafibranor in primary biliary cholangitis. New England Journal of Medicine, 390(9), 795-805. https://www.nejm.org/doi/full/10.1056/NEJMoa2306185

Madrial Pharmaceuticals, Inc. (14 March, 2024). Madrigal pharmaceuticals announces FDA approval of Rezdiffra™ (resmetirom) for the treatment of patients with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis. [Website, accessed 13 January 2025]. https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-fda-approval-rezdiffratm

Takeda. (18 April, 2024). U.S. FDA approves subcutaneous administration of Takeda’s ENTYVIO® (vedolizumab) for maintenance therapy in moderately to severely active Crohn’s Disease. [Website, accessed 13 January, 2025]. https://www.takeda.com/newsroom/newsreleases/2024/fda-approves-subcutaneous-administration-of-entyvio/

U.S. Food and Drug Administration. (7 January, 2025). Novel Drug Approvals for 2024. [Website, accessed 13 January, 2025]. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024