Rare Disease Day: seven drugs awaiting approval in 2025

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A rare disease is one that strikes fewer than 65 per 100,000 people, according to the World Health Organization. Treating these conditions is particularly challenging because of the small patient population, making it hard to conduct trials and properly understand the disease. Medicines that are used to treat rare diseases are often granted orphan drug status to bring in investors to develop and commercialize the drugs, which would be beneficial for millions of people diagnosed with such conditions. As we observe Rare Disease Day today, let us take a look at seven drugs poised to be approved to address rare diseases in 2025.

Diazoxide choline

Prader-Willi syndrome is a genetic disorder that affects around one in every 15,000 births, according to the Prader-Willi Research. The condition was first described in 1956 by Swiss doctors, and since then, it has been researched to bring treatments to the table.

It is caused by a mutation in chromosome 15 and can result in symptoms such as short stature, floppiness caused by weak muscles, and behavioral challenges like obsessive-compulsiveness, skin picking, and difficulty regulating emotions. The most common symptom associated with the syndrome is insatiable appetite, which is known as hyperphagia. This is the symptom that diazoxide choline is designed to treat.

Although not a cure, California-based Soleno Therapeutics’ diazoxide choline is up for review by the U.S. Food and Drug Administration (FDA) to treat Prader-Willi syndrome, and a decision is expected in March 2025. How the drug works is that it activates potassium channels – which allows potassium ions to pass through cell membranes – in the brain to reduce the secretion of two chemicals that regulate feelings of hunger. So, by bringing the levels of these chemicals down, the appetite can be modulated better in patients.

While the drug did not seem promising in 2020 when topline phase 3 results showed that it failed to meet the primary endpoint, it later demonstrated significant improvement in hyperphagia in patients. It has since been granted breakthrough therapy and new drug designations by the FDA.

Fitusiran

Fitusiran is an investigational siRNA therapy for the prophylactic treatment of people with hemophilia A and B, both of which are inherited bleeding disorders that occur when there are low levels of certain blood clotting factors – a deficiency of factor 8 in hemophilia A and of factor 9 in hemophilia B.

It is designed to lower antithrombin, a protein in the blood that prevents blood clots from forming, in order to avoid bleeds. In two phase 3 trials, the drug candidate – owned by French pharma giant Sanofi and developed by Massachusetts-based Alnylam Pharmaceuticals – achieved primary and secondary endpoints. It demonstrated significant and clinically meaningful improvements in bleed protection across all hemophilia populations.

In the first trial, 66% of participants with inhibitors – people with antibodies that can prevent clotting factor treatments from working – who received the monthly treatment experienced zero bleeding episodes compared to 5% who were given a bypassing agent after nine months of treatment.

The second study showed that 51% of participants without inhibitors who received fitusiran monthly experienced zero bleeds compared to 5% in the comparator group.

It received breakthrough therapy designation from the FDA in 2023. Its success in the clinic makes it one to watch out for in the blood disorder space.

Elamipretide

Estimated to affect around one in 300,000 to 400,000 births, Barth syndrome is a rare disease that affects the heart, muscles, and the immune system. It is characterized by skeletal muscle weakness, delayed growth, fatigue, varying degrees of physical disability, heart muscle weakness, or cardiomyopathy, low white blood cell count, and a condition called methylglutaconic aciduria – a metabolic disorder that prevents the body from producing energy in the mitochondria, the powerhouse of the cell.

To date, there are no therapies that have been approved by U.S. or European regulators. But that could change this year. Elamipretide is a small molecule that was granted priority review designation by the U.S. Food and Drug Administration (FDA) last year for Barth syndrome and could bag approval this year. It is designed to improve mitochondrial function by binding to cardiolipin – a type of fat molecule present in the mitochondria. This binding stabilizes the mitochondrial membrane and reduces oxidative stress. This way, elamipretide can potentially improve heart function and muscle strength.

In the clinic, Massachusetts-based Stealth BioTherapeutics-owned elamipretide has been found to increase mitochondrial respiration and improve electron transport chain function and ATP production. The New Drug Application was accepted by the FDA in April, and the FDA is expected to make a call soon. The drug is also being investigated to treat rare neuromuscular diseases, such as primary mitochondrial myopathy – a group of disorders that are associated with changes in genetic material in the DNA of the mitochondria leading to issues with muscle function – as well as dry age-related macular degeneration (AMD) – a condition linked to the gradual thinning of the macula in the eye that causes vision loss.

Nipocalimab

Several monoclonal antibodies have been given the go-ahead in the past to treat rare diseases, such as Cablivi for the blood disorders thrombotic thrombocytopenic purpura, Adakveo for symptoms of sickle-cell disease, and Tepezza for thyroid eye disease. Soon, there could be another one in the mix.

Pharma giant Johnson & Johnson’s nipocalimab is a monoclonal antibody designed to block the protein FcRn in order to reduce levels of circulating immunoglobulin G (IgG) antibodies in myasthenia gravis, a chronic autoimmune disease. It is caused by a signaling issue between the nerves and the muscles, leading to muscle weakness in the body.

A phase 3 study found that it is the first and only FcRn blocker to demonstrate superiority in activities of daily living (MG-ADLa) over placebo when added to standard of care over 24 weeks in patients who possess autoantibodies associated with the disease. The Myasthenia Gravis Activities of Living (MG‐ADL) scale is a patient‐reported scale that measures myasthenia gravis symptoms.

Patients who were given nipocalimab along with the standard of care improved by 4.7 points on the MG-ADL scale, which was significantly more than the 3.25-point improvement from baseline observed in the placebo and standard of care cohort.

The FDA granted a priority review to nipocalimab in January, and the European Medicines Agency (EMA) has also received a marketing authorization application for the drug. It is also being tested to potentially treat other chronic autoimmune conditions like Sjögren’s disease – affects the glands that produce tears and saliva – and warm autoimmune hemolytic anemia – a condition that causes the body to destroy red blood cells.

Plozasiran

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that affects around one to two people per million. It is a metabolic condition that prevents the body from breaking down fat molecules called triglycerides. In most cases of FCS, the enzyme lipoprotein lipase is either absent or not working properly. The drug candidate Plozasiran targets a molecule called apolipoprotein C-3 (APOC3) in the blood, which is responsible for regulating levels of triglycerides.

The drug owned by U.S.-based Arrowhead Pharmaceuticals is an RNA interference (RNAi) medicine. An RNAi drug essentially silences the production of specific genes that cause disease or contribute to diseases. Plozasiran has demonstrated reductions in triglycerides and multiple lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia – all of which are metabolic conditions caused by increased levels of triglycerides – across studies.

In one such late-stage study, plozasiran reduced triglycerides by 80% from baseline and reduced the risk of patients developing acute pancreatitis – a sudden inflammation of the pancreas and a major complication of FCS – by 83%.

Typically, patients with FCS maintain a low-fat diet in order to not trigger symptoms, but this is only to manage things and not address the root cause of these symptoms, which Plozasiran aims to do. If the drug nabs FDA approval by the end of this year, it would go head-to-head with American biotech Ionis Pharmaceuticals’ Tryngolza, the first and only RNAi drug to treat the rare disease and cleared by regulators in December.

Sebetralstat

A kallikrein inhibitor is a drug that blocks the activity of kallikrein, an enzyme that is involved in blood clotting and inflammation, among other processes. Sebetralstat is a kallikrein inhibitor that is used to treat a rare disease called hereditary angioedema (HAE).

People with HAE experience painful episodes of swelling in the body. Sometimes, this swelling can occur in the airways of the lungs or the intestinal walls, making it potentially life-threatening. Sebetralstat works by selectively inhibiting plasma kallikrein, which in turn decreases inflammatory molecules associated with HAE.

If approved, sebetralstat would be the first oral on-demand treatment for HAE. Its potential approval would be based on its success in a phase 3 trial, which was revealed last year. The drug developer Massachusetts-based KalVista Pharmaceuticals held the study, which met all its primary and secondary endpoints. People with HAE who were treated with both 300 mg and 600 mg of sebetralstat achieved symptom relief much quicker than those who were given the placebo.

Taletrectinib

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. However, ROS1-positive NSCLC affects only around 1-2% of people with NSCLC, which amounts to 18,500–37,000 new cases globally each year. Taletrectinib is an oral tyrosine kinase inhibitor that inhibits the protein ROS1 to halt tumor growth.

Developed by California-based Nuvation Bio, taletrectinib saw encouraging results in a pivotal phase 2 trial. Tumors shrank in 89% of the patients treated with taletrectinib who hadn’t previously been given a tyrosine kinase inhibitor before, and in 56% of those who were pretreated with a tyrosine kinase inhibitor.

The drug exhibited durable responses and prolonged progression-free survival (PFS) with long-term follow-up. The median duration of response and median progression-free survival in tyrosine kinase inhibitor-naive patients were 44 months and 46 months, respectively.

The drug was authorized in China in January and is currently being reviewed by the FDA. Taletrectinib has previously snagged breakthrough therapy and orphan drug designations. The drug’s approval in the U.S. would mean a new and effective treatment option for patients with ROS1-positive NSCLC, especially those who have not responded well to other ROS1 tyrosine kinase inhibitors in the past.

Rare diseases: how can R&D be improved?

As mentioned previously, developing drugs for rare diseases has its own hurdles. According to Neil Ward, vice president of Europe, the Middle East, and Africa at PacBio, there is a lot of work to be done in the rare disease space. Despite positive government-backed investment in genomics projects centered around rare diseases, “patients still typically face a grueling four to five-year diagnostic odyssey, with 60% failing to get an answer even after numerous tests,” Ward explained.

“Without a diagnosis or an understanding of the genetic cause of a rare disease, targeted treatment or proper care becomes extremely challenging,” said Ward.

Research and development (R&D) requires much more investment, particularly in fields such as genome sequencing, Ward pointed out.

“One promising approach is long-read sequencing, which analyzes the genome in much longer stretches, enabling the detection of complex variants often missed by traditional methods,” said Ward. “While long-reads come with higher upfront costs, they could ultimately streamline diagnostics and work out more cost-effective methods by replacing multiple tests with a single comprehensive analysis. Crucially, R&D can only progress if we gain a complete picture of the genetic underpinnings of rare diseases – something long-reads are uniquely positioned to provide.”

As rare disease research is not a solitary pursuit, Ward thinks that the only way forward is to drive faster diagnoses in order to know what treatment is best suited for people to ultimately transform the landscape for patients worldwide.