2024 has witnessed the approval of a number of medicines including first-in-class drugs like Rezdiffra for chronic liver disease, Duvyzat for a rare muscular disorder, and Winrevair for a rare condition that causes blood pressure in the lungs. In this article, we look at eight much-awaited drugs that have been approved by regulators.
Table of contents
Rezdiffra
A first for the potentially life-threatening liver condition metabolic dysfunction-associated steatohepatitis (MASH), Rezdiffra received the green light from the U.S. Food and Drug Administration (FDA) to treat the disease back in March. MASH occurs when the body begins to store fat in the liver, causing inflammation. Chronic inflammation can scar the tissues, which can lead to cirrhosis (liver damage), and even liver failure.
American biotech Madrigal Pharmaceuticals’ accelerated approval came after the drug had a successful phase 3 trial where there was reduction in non-alcoholic fatty liver disease (NAFLD) activity score – a measure to evaluate MASH treatment response – and fibrosis improved in patients. These two endpoints were consistent in the 1,759 patients regardless of age, gender, type 2 diabetes status, or fibrosis stage.
Since its approval, clinical trial wins have been on the rise, with hopes that more drugs could broaden treatment options for more than 115 million people who struggle with the symptoms worldwide.
Duvyzat
Duchenne muscular dystrophy is a rare muscular disorder that affects children, mostly boys – one in 3,500 – and is typically managed with the help of steroids, which improve muscle strength but also come with a number of side effects. Until now. The FDA’s approval of Duvyzat marks the first non-steroidal drug to treat patients with all genetic variants of the fatal muscle disease.
Italian multinational Italfarmaco’s Duvyzat was greenlit after a clinical trial showed that the drug reduced muscle decline by 40% based on a four-stair climb test – a tool to assess motor function in patients. The study was conducted in 179 boys aged six and older who were given the drug twice a day along with steroids.
Duvyzat is a histone deacetylase (HDAC) inhibitor that blocks histone deacetylases, a group of enzymes that turn genes on and off and limit the ability of muscles to be regenerated. By blocking HDAC, Duvyzat slows muscle deterioration.
Side effects of the oral drug include diarrhea, abdominal pain, and a decrease in platelets, which can lead to increased bleeding.
Duvyzat’s clearance comes a year after Sarepta Therapeutics’ gene therapy ELEVIDYS was approved. ELEVIDYS, the world’s second-most expensive drug – costing $3.2 million – is prescribed for children aged four and five who have a mutation in the dystrophin gene.
Anktiva
Bladder cancer affects hundreds of thousands of people every year globally. In the case of non-muscle-invasive bladder cancer (NMIBC), where the cancer cells are in the bladder’s inner lining, the Bacillus Calmette-Guérin (BCG) vaccine – which has been rolled for tuberculosis prevention – is given to patients to get rid of the cancer cells. However, some patients become resistant to BCG treatment. Anktiva, which was cleared by the FDA in April, is now prescribed along with the BCG immunotherapy to treat BCG-unresponsive non-muscle invasive bladder cancer.
California-based ImmunityBio’s drug is an IL-15 agonist immunotherapy that activates cancer-killing immune cells including natural killer cells and memory T cells. As memory cells that are specifically trained to recognize cancer cells are switched on, it is able to induce a durable complete response in patients. The approval came after the drug achieved a 62% complete response rate in 77 patients.
The win comes after an FDA rejection of the drug last year owing to manufacturing concerns. Now, it gives competition to pharma giant Merck’s immunotherapy drug Keytruda and Swiss multinational Ferring Pharmaceuticals’ gene therapy Adstiladrin in BCG-unresponsive NMIBC.
Winrevair
Pulmonary arterial hypertension is a rare condition that causes high blood pressure in the lungs, which leads to symptoms like shortness of breath and fatigue that can get worse with time. Winrevair, owned by the pharma giant Merck after its acquisition of Massachusetts-based Acceleron, is the first treatment of its kind to be cleared for pulmonary arterial hypertension.
In a therapeutic market dominated by receptor agonists like Johnson & Johnson’s Uptravi and Opsumit – after its buyout of Swiss pharma Actelion – Winrevair is shaking things up as an activin signaling inhibitor. It binds to the growth factor activin A to improve cell growth and proliferation and reduce inflammation.
When the drug was given to patients with the lung disease, who were already taking standard of care medication, it increased the six-minute walk distance by 41 meters after 24 weeks, according to a phase 3 trial. The combination therapy also slashed the risk of death by 84% compared to standard of care therapy on its own.
Hemoglobin levels of patients on the therapy are monitored as it may increase the hemoglobin count, which could lead to a condition called erythrocytosis.
A vial of the drug, which is dosed every three weeks, is priced at $14,000, making the annual out-of-pocket cost of the drug $238,000 in the U.S.
Imetelstat
The anti-cancer drug imetelstat received approval by the FDA earlier this month to treat myelodysplastic syndromes (MDS), a type of cancer in which immature blood cells do not fully mature to become healthy cells. But it hasn’t been smooth sailing for telomerase inhibitors – the class of drugs that imetelstat belongs to – which was once poised to be a “magic bullet” against aging.
A telomere is the cap on chromosomes that protect them from damage. As cells continue to divide with aging, telomeres get shorter until they get to a certain size, disrupting cell division. American biotech Geron first discovered the potential of telomere inhibitors in prolonging aging around three decades ago. But since then, the drug hasn’t lived up to the hype and had clinical failures in cancer as well.
Nevertheless, positive results from a phase 3 trial led to its approval for MDS. Imetelstat, now known under the brand name Rytelo, is designed to bind to the telomerase enzyme to curb its activity and kill cancer cells. The study found that the drug was able to reduce transfusion burden in those with lower-risk MDS. Nearly 40% of the patients did not need transfusions at the end of eight weeks compared to 15% on placebo.
The drug has been linked to low platelet and white blood cell levels in the blood.
mRNA-1345
The therapeutic field of the infectious disease caused by the respiratory syncytial virus (RSV) is burgeoning with big pharma drugs like GSK’s Arexvy and Pfizer’s ABRYSVO. Now, Moderna – famed for its mRNA COVID-19 vaccines – has joined the space with its mRNA-1345 vaccine.
The vaccine was granted approval under a breakthrough therapy designation making it the first mRNA vaccine after the COVID-19 vaccine to be authorized. A global phase 3 trial of the vaccine had 37,000 patients aged 60 and older in 22 countries. Its efficacy was found to be 83.7% at the median follow-up of 3.7 months.
mRNA-1345 may have an edge over Arexvy and ABRYSVO as it would be the only vaccine available in a pre-filled syringe making it more convenient to administer. This could potentially cut wait times for patients to receive the dose.
The vaccine is expected to be rolled out by this fall, which would be peak RSV season until spring in the U.S.
Beqvez
Hemophilia B is a rare clotting disorder caused by the lack of blood clotting factor IX because of a mutation in the F9 gene. Multinational biotech CSL Behring’s gene therapy Hemgenix was given the FDA nod to treat hemophilia B back in 2022. Priced at $3.5 million, it is among the world’s most expensive drugs. Now, about to compete with it is one-time gene therapy Pfizer’s Beqvez – initially developed by American biotech Spark Therapeutics before it was bought by the pharma giant – which costs the same as Hemgenix.
The therapy, which has been backed by Health Canada, the FDA, and the European Medicines Agency (EMA), is similar to Hemgenix. It aims to cut the need for regular infusions in patients as it delivers a functional copy of the FIX gene enclosed in an adeno-associated virus (AAV) vector. The drug was authorized after it met the primary endpoint in a phase 3 trial.
A mean annualized bleeding rate (ABR) – a measure for the number of reported bleeding events – of 2.5 was observed among patients who received BEQVEZ in the efficacy evaluation period compared to a mean ABR of 4.5 during the pre-treatment period of at least six months. Moreover, in 60% of patients, bleeds were eliminated compared to 29% in the prophylaxis cohort.
Vafseo
Anemia, a condition where the body does not have enough red blood cells to carry oxygen to the body’s tissues, is a common complication of chronic kidney disease (CKD). To tackle this, Massachusetts-based Akebia Therapeutics’ Vafseo was given the go-ahead from the FDA after being denied clearance two years ago.
The drug contains the active substance vadadustat, which mimics an enzyme called hypoxia-inducible factor prolyl hydroxylase (HIF-PH). This enzyme stimulates the production of a hormone linked to red blood cell production called erythropoietin, which is often present in inadequate amounts in patients with anemia.
The drug is prescribed in 37 countries to patients with CKD-associated anemia who have been receiving dialysis for at least three months.
If not for the two-year wait due to its initial FDA rejection, the drug would have been the first of its kind to treat anemia in patients with CKD. However, pharma giant GSK’s oral drug Jesduvroq nabbed the ‘first-in-class’ title for the indication last year.
The approval comes with a warning regarding myocardial infarction – caused by blood clotting in the heart – stroke, blood clots in the veins, and even an increased risk of death.
Honorable mentions
This year has also been a win for patients with rare diseases like WHIM syndrome. Warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome is an immunodeficiency where people are prone to bacterial infections. Massachusetts-based X4’s Xolremdi addresses the root cause of the disease unlike antibiotics or immunoglobulins, which are typically prescribed. It aids in the movement of white blood cells in and out of the bone marrow to be on the lookout for infections.
As for cancer therapies, apart from Rytelo and Anktiva, the FDA greenlit Amgen’s T-cell engager Imdelltra for small-cell lung cancer and BeiGene’s monoclonal antibody Tevimbra for esophageal squamous cell carcinoma this year.
Later this year, regulators will make key decisions on Karuna’s schizophrenia drug KarXT and Daiichi Sankyo and AstraZeneca’s antibody drug conjugate datopotamab deruxtecan that targets breast and lung cancers, as patients and the healthcare community wait in anticipation to see how things play out.