Groundbreaking Drug Launches
Olezarsen (TRYNGOLZA)
Mechanism of Action: Apolipoprotein C-III expression inhibitors; Gene silencing Drug class: Drug conjugates Originator: Ionis Pharmaceuticals Indication: Hyperlipoproteinaemia type I (Familial chylomicronemia syndrome)
Approval date: 19 December 2024 Trials: BALANCE
Hyperlipoproteinaemia type I
Hyperlipoproteinemia Type I, or hyperchylomicronemia, is an autosomal recessive disorder caused by a defect in lipoprotein lipase, leading to impaired clearance of chylomicrons and triglycerides from the blood. This results in the buildup of chylomicrons and triglycerides in the plasma, which can cause acute pancreatitis, hepatosplenomegaly, xanthomas, and other lipid-related complications. Treatment primarily involves dietary changes.
Prevalence Type 1 hyperlipoproteinemia, also referred to as familial hyperchylomicronemia, is an exceptionally rare condition, with an estimated prevalence of approximately 1 in 1,000,000 individuals.
Treatment challenges The therapeutic management of hyperlipoproteinemia (a) has garnered considerable attention, as significant reductions in Lp(a) levels may potentially reduce cardiovascular risk. For patients with mild to moderate elevations in Lp(a) levels, treatments such as aspirin, niacin, estrogens, and statins, which target different molecular pathways, may be prescribed. In more severe cases, other therapeutic options, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Lp(a) apheresis, and the novel antisense oligonucleotide, Pelacarsen, which are currently being evaluated in clinical trials, have shown promising results. These treatments could offer potential benefits for patients with severe hyperlipoproteinemia. However, these therapies may cause various side effects, including: • Nausea or indigestion • Headaches • Nosebleeds • Sore throat • Cold-like symptoms (a runny or blocked nose, & sneezing) • Constipation or flatulence • Diarrhea
Why is Olezarsen poised to make an impact in 2025?
Ionis Pharmaceuticals received approval from the U.S. Food and Drug Administration (FDA) in December 2024 for a new therapy aimed at treating a rare and life-threatening genetic disorder that prevents the body from properly breaking down fats. This approval marks the company's first-ever solo drug launch in its 35-year history. Its approval makes this drug the first treatment to be approved for familial chylomicronemia syndrome (FCS) in the United States. Should the drug gain approval for more widespread conditions, market analysts project that Tryngolza could generate peak sales of $1.8 to $2 billion.
Regulatory milestones
Registrational Trial
The U.S. Food and Drug Administration (FDA) has approved TRYNGOLZA (olezarsen) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) based on results of BALANCE trial.
BALANCE:
A phase 3 clinical trial aimed to evaluate the efficacy and safety of olezarsen, a ligand-conjugated antisense medication, in individuals aged 18 and older with genetically confirmed FCS (NCT04568434).
“Tryngolza significantly reduced triglyceride levels by 42.5% at 6 months and 57% at 12 months compared to placebo”