3 new drugs are coming for rare and chronic conditions

Competitive environment

Previously established standard of care for sHTG includes statins, fibric acid derivatives (eg, fenofibrate) and omega-3 fatty acids. Although statins provide only modest triglyceride reductions, they are used first-line in patients with sHTG because of their cardioprotective effects. Fibric acid derivatives and prescription omega-3 fatty acids are commonly added to further lower triglycerides and reduce the risk of acute pancreatitis. 

Despite the availability of these options, many patients continue to have severely elevated triglycerides and are at increased risk of acute pancreatitis.

Tryngolza represents the first novel therapy targeting elevated triglycerides in this population in decades. In clinical trials, Tryngolza significantly reduced triglyceride levels when added to existing standards of care and was associated with a significant reduction in the risk of acute pancreatitis. 

Acute pancreatitis events in the trials were concentrated in patients at high risk (86% of cases), defined as a baseline triglyceride level of ≥ 880 mg/dL and a history of pancreatitis. For those patients, the number needed to treat to prevent 1 acute pancreatitis event over 1 year was 4. 

This new indication substantially expands the eligible population for Tryngolza compared with the previous FCS indication, which only affects up to 5,000 people in the U.S. However, treatment options for sHTG have been well established and mostly available as generic drugs. In the pivotal Tryngolza studies, patients remained on standard-of-care drugs, and approximately 60% to 70% were receiving at least two lipid lowering therapies at baseline. 

In addition, outcomes data are not available to determine whether Tryngolza reduces the risk of cardiovascular events. Taken together, these factors suggest Tryngolza will likely be used as a second- or third-line option in clinical practice for sHTG.

Looking ahead, Ionis may face competition from Arrowhead Pharmaceuticals’ apoC-III-targeted therapy, Redemplo® (plozasiran). Redemplo is currently approved for FCS and is in development for sHTG, with Phase 3 trial data for sHTG expected in the second half of 2026.

The wholesale acquisition cost for Tryngolza was approximately $595,000 per year. However, as of April 1, 2026, Ionis reduced the price by 93% to approximately $40,000 per year. Commonly used generic fibrates and omega-3 fatty acids used for sHTG are relatively inexpensive and cost approximately $140 (fenofibrate) to $2,200 (icosapent ethyl) per year. 

Competitive environment

The standard of care for narcolepsy includes “wake promoting agents” such as Nuvigil® (modafinil), Provigil® (armodafinil), Sunosi® (solriamfetol) and Wakix® (pitolisant). 

• For patients who require additional treatment for daytime sleepiness, options include traditional stimulants such as Ritalin® (methylphenidate) and sodium oxybate products (e.g., Xyrem®). 
• For patients with cataplexy, FDA approved therapies include Wakix and sodium oxybate (both can provide relief for daytime sleepiness and cataplexy) and off-label use of antidepressants (e.g., venlafaxine). 

Due to differences in mechanism, patients are often treated with multiple drugs to alleviate their symptoms.

Oveporexton would provide a novel mechanism of action for the treatment of narcolepsy with cataplexy, and it addresses a key deficiency (orexin) causing the disease. While there are no head-to-head trials comparing oveporexton vs. the current standards of care, the data for oveporexton appear promising. Indirect comparisons suggest greater improvements in daytime sleepiness measures vs. drugs like Provigil, sodium oxybate and Wakix, and similar efficacy to sodium oxybate for reductions in cataplexy. 

An analysis by the Institute for Clinical and Economic Review (ICER) found that treatment with oveporexton resulted in statistically and clinically significant increases on the Maintenance of Wakefulness Test of approximately 15 minutes vs. sodium oxybate and modafinil/armodafinil, and 18 minutes vs. pitolisant. However, oveporexton would enter a competitive treatment landscape with well-established alternatives, including some drugs with generic availability (e.g., modafinil, sodium oxybate). 

Key limitations for oveporexton include:

• Lack of long-term safety data for this novel mechanism.
• No data with use in combination with other narcolepsy therapies.

For reference, the wholesale acquisition cost for Wakix, the last novel drug approved for narcolepsy and cataplexy, is approximately $162,000 per year.

Competitive environment

The current standard of care for dermatomyositis includes glucocorticoids like prednisone, disease-modifying antirheumatic drugs (DMARDs) (e.g., methotrexate, and intravenous immune globulin (IVIG). Prednisone is usually the first-line therapy and can provide a complete response in select patients. However, many require long-term therapy, where tolerability and cumulative steroid-related adverse effects can become an issue.

Brepocitinib would represent a novel mechanism of action and the first targeted therapy for the treatment of dermatomyositis. In the pivotal study, patients who were resistant to previous therapy showed improvements across a range of clinical endpoints with the higher dose of brepocitinib vs. placebo. Notably, brepocitinib also increased the likelihood of reduced use of glucocorticoids, supporting an expected role as a steroid-sparing option in practice.

While it may provide benefit in reducing or eliminating the need for glucocorticoids, brepocitinib is a TYK2/JAK1 inhibitor, which means it will likely carry safety risks and boxed warnings similar to other JAK inhibitors (e.g., serious infections). In addition, there is an absence of head-to-head comparisons vs. commonly used therapies such as DMARDs and IVIG.

Finally, the initial indication is expected to be limited to adults. While dermatomyositis predominantly affects older adults, pediatric disease does occur. 

For reference, the wholesale acquisition cost for Rinvoq® (upadacitinib), one of the newer and more commonly used JAK inhibitors for chronic inflammatory conditions, is approximately $86,000 per year. However, neither Rinvoq nor any other JAK or TYK2 inhibitor is approved for dermatomyositis. 

JAK inhibitors that are approved for rare diseases are more expensive compared to drugs in the class for chronic inflammatory diseases. For reference, the wholesale acquisition cost for Ojjaara® (momelotinib), a JAK1 and JAK2 inhibitor approved for myelofibrosis (a rare type of blood cancer), is approximately $360,000 per year.