8 of the most expensive drugs in biopharma: Unraveling the costliest medications

Most expensive drugs

As the years have gone by, the price of drugs has risen. According to an analysis by Reuters,  the average price of new drugs increased by 35% in the U.S. in 2023 compared to the previous year, reflecting in part the industry’s embrace of expensive therapies for rare diseases like muscular dystrophy. Gene therapies in particular have emerged as some of the costliest treatments around, largely due to their curative potential and the fact that they only need to be administered once. In this article, we take a look at eight of the world’s most expensive drugs. 

Table of contents

    Lenmeldy

    Cost: $4.25 million 

    Company: Orchard Therapeutics

    After being given the green light just last month, Lenmeldy is the first U.S. Food and Drug Administration (FDA)-approved gene therapy for the treatment of children with metachromatic leukodystrophy (MLD), a rare and potentially fatal genetic disease affecting the brain and nervous system caused by a deficiency of an enzyme called arylsulfatase A (ARSA). This leads to a buildup of sulfatides (fatty substances), which destroy the protective layer of the nerves called the myelin sheath. Patients eventually lose the ability to move, talk, swallow, eat, and see. It is estimated that MLD affects one in every 40,000 individuals in the U.S. 

    Lenmedly is a one-time treatment made from the patient’s own hematopoietic stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. Once the stem cells have been collected and modified ex-vivo, they are then infused back into the patient where they engraft (attach and multiply) within the bone marrow, eventually migrating across the blood-brain barrier into the central nervous system and expressing the functional enzyme. 

    When Orchard Therapeutics announced on March 20 that Lenmeldy would cost $4.25 million, it officially became the world’s new most expensive drug. The company said that the price reflects the value the therapy could deliver to eligible patients and their families, as well as the potential long-term impact the treatment may have on overall healthcare utilization, minimization of productivity loss for caregivers, and life opportunities for patients.

    Hemgenix

    Cost: $3.5 million

    Company: uniQure, CSL Behring

    On our list of the most expensive drugs, Hemgenix, developed by Amsterdam-based biotech uniQure in partnership with global biopharma CSL Behring, is a one-time gene therapy for adults with hemophilia B. The condition is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps to form blood clots. As a result, the disease makes people vulnerable to bleeding in their joints, muscles, and internal organs, which causes pain, swelling, and joint damage. 

    Hemgenix reduces the rate of abnormal bleeding in people with hemophilia B by enabling the body to continuously produce factor IX. It is an adeno-associated virus (AAV) vector-based gene therapy, using an AAV5 vector to carry genetic DNA instructions to the liver, where factor IX proteins are then generated. These genetic instructions remain in the target cells but generally do not become a part of a person’s own DNA. Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of factor IX. The therapy was approved in 2022, and was described as a “game changer” in hemophilia B treatment. 

    Patients with hemophilia B typically require regular prophylactic infusions of factor IX, which becomes extremely expensive over a lifetime. CSL Behring told Fierce Pharma at the time of approval that, despite the $3.5 million price tag, the drug would generate “significant cost savings for the overall healthcare system” and “significantly lower the economic burden of hemophilia B by reducing annual bleed rates, reducing or eliminating prophylactic therapy and generating elevated [factor] IX levels that last for years.” 

    Elevidys

    Cost: $3.2 million

    Company: Sarepta Therapeutics 

    When Sarepta Therapeutics’ Elevidys gained accelerated approval from the FDA in June 2023, it became the first gene therapy for the treatment of pediatric patients from four to five years of age with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. An inherited degenerative disease that results in muscle weakness and loss of muscle tissue, DMD is the most common childhood form of muscular dystrophy and typically occurs in boys, affecting around one in 3,300. It worsens over time and the average life expectancy is around 27 years. 

    Elevidys is a one-time therapy designed to treat the underlying cause of DMD, which involves a dystrophin gene mutation that yields low levels of the dystrophin protein that is needed to strengthen muscle fibers. The gene therapy, therefore, works by delivering a gene that codes for a functional shortened dystrophin (called Elevidys micro-dystrophin) into the muscle tissue.

    According to BioPharma Dive, at the time of approval, Sarepta’s chief executive officer (CEO) Doug Ingram defended the $3.2 million price tag (making it one of the most expensive drugs), saying that the price actually reflected a “conservative” approach to valuing the benefit to patients and their families of Elevidys, which Sarepta claimed would only be cost-effective at prices between $5 million and $13 million.

    Skysona

    Cost: $3 million

    Company: Bluebird bio 

    In 2022, four weeks after bluebird bio won FDA approval for their gene therapy Zynteglo, the company also earned approval for Skysona. When Zynteglo was approved, it momentarily became the highest priced drug in U.S. history at $2.8 million. But not for long, as bluebird decided to price Skysona even higher, making it available at a cost of £3 million. Chief commercial and operating officer Tom Klima justified the price during the company’s quarterly presentation last year, stating that it was a “data-driven” process that took into “consideration the positive clinical outcomes, quality of life improvements, health system cost savings and potential societal impact of patients and families.”

    Skysona, which is another gene therapy, was approved as the first treatment to slow the progression of neurologic brain dysfunction in boys aged 4 to 17 years with early, active cerebral adrenoleukodystrophy (CALD). CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes irreversible, devastating neurologic decline, including major functional disabilities such as loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. Nearly half of patients who do not receive treatment die within five years of symptom onset.

    Skysona is made from the patient’s own stem cells and is modified to contain a copy of the gene to make a functional enzyme called ALDP (adrenoleukodystrophy protein), whose production is prevented due to a mutation in the ABCD1 gene in people with CALD. This mutation prevents the breakdown of very long-chain fatty acids and ultimately resulting in destruction of the sheath (myelin) that surrounds the nerve.

    Zynteglo

    Cost: $2.8 million 

    Company: Bluebird bio

    After bluebird won regulatory approval in Europe for its beta-thalassemia treatment Zynteglo in 2019, the company set the price of the treatment at €1.575 million ($1.8 million), which makes it one of the most expensive drugs. But, unable to reach a consensus with authorities in Europe around fair gene therapy pricing, bluebird announced its departure from Europe in August 2021, calling the pricing situation “untenable” and the market “broken.” When bluebird then received FDA approval for Zynteglo in the U.S. in 2022, the market was more forgiving, allowing the company to price its gene therapy at $2.8 million. Although the price tag came as a shock to many, bluebird said that it works out cheaper than current beta-thalassemia treatment options.

    At the time of its approval, Zynteglo became the first cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions. Beta-thalassemia is a type of inherited blood disorder that causes a reduction of normal hemoglobin and red blood cells in the blood, through mutations in the beta-globin subunit, leading to insufficient delivery of oxygen in the body. Transfusion-dependent beta-thalassemia is the most severe form of the condition and generally requires life-long red blood cell transfusions as the standard course of treatment, which is a lengthy process that patients typically undergo every two to five weeks.

    Zynteglo works by adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. The gene is added into a patient’s cells ex-vivo and is then infused into the patient, resulting in normal or near-normal levels of total hemoglobin and eliminating the need for regular red blood cell transfusions. 

    Casgevy

    Cost: $2.2 million

    Company: Vertex Pharmaceuticals, CRISPR Therapeutics

    Casgevy’s approval by the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA) in November 2023 marked the first time a CRISPR-based gene therapy had ever been given the green light. Shortly after, in December 2023, it was also approved by the FDA for the treatment of sickle cell disease, before the regulatory agency widened its U.S. approval in January 2024, stating that the therapy could also be used to treat transfusion-dependent beta-thalassemia.  

    As a one-time gene therapy, Casgevy could prove to be a cure for patients. It works by turning on a gene called fetal hemoglobin, which people naturally have as fetuses, as well as when they are born. This gene prevents people with sickle cell disease or beta-thalassemia from experiencing symptoms until it turns off later in life. Therefore, Casgevy is designed to target a gene called BCL11A, which usually prevents the production of fetal hemoglobin in adults. It is administered by taking blood-producing stem cells from the bone marrow of people with sickle cell disease or beta-thalassemia, before using CRISPR/Cas9 to edit the genes encoding hemoglobin. Once the Cas9 enzyme reaches BCL11A, it cuts both DNA strands and disables the gene, before the modified stem cells are then infused back into the patient, giving rise to red blood cells containing fetal hemoglobin. 

    According to an SEC filing, Casgevy is priced at $2.2 million, making it one of the most expensive drugs. However, Vertex and CRISPR have said that, in the U.S., healthcare costs to manage transfusion-dependent beta-thalassemia are estimated to be more than $5 million over a person’s lifetime. This would make the one-time therapy cheaper in the long run.

    Zolgensma 

    Cost: $2.1 million

    Company: Novartis

    Zolgensma came with a price tag of $2.1 million when it was approved by the FDA back in 2019, which made it the most expensive drug on record at that time. It is intended as a one-shot gene therapy to treat pediatric patients with spinal muscular atrophy (SMA), a rare disease caused by a mutation in the survival motor neuron 1 (SMN1) gene and a leading genetic cause of infant mortality. If given at birth before symptoms develop, Zolgensma could be a cure. However, the older the baby gets, the less effective and riskier the treatment. According to reports at the time of approval, this left families scrambling to find the money to pay for the treatment. 

    The SMN1 gene encodes the survival motor neuron (SMN) protein, which is found throughout the body and is critical for the maintenance and function of specialized nerve cells, called motor neurons. Motor neurons in the brain and spinal cord control muscle movement throughout the body. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. SMA caused by mutations in the SMN1 gene is generally classified into several subtypes, based on the age of onset and severity, with infantile-onset SMA being the most severe and most common subtype.

    Zolgensma is an AAV vector-based gene therapy that targets the root cause of SMA. The vector delivers a fully functional copy of the human SMN gene into the target motor neuron cells. This results in the expression of the SMN protein in a child’s motor neurons, improving muscle movement and function, as well as survival. 

    Myalept

    Cost: $1.26 million

    Company: Chiesi Farmaceutici

    Until the gene therapies listed above came into the picture, Myalept consistently held a leading position in annual rankings of the world’s most expensive drugs, costing patients around $1.26 million a year. It is given as a subcutaneous injection once a day and patients can be taught to self-administer the medicine at home. One vial of the drug goes for $5,867.52 and doses are weight-based. Patients generally use an average of 18 vials per month.

    Now owned by Chiesi Farmaceutici after the Italian company acquired Amryt Pharma in January 2023, the medicine was approved by the FDA back in 2014 as a replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital or acquired generalized lipodystrophy. Lipodystrophy is a group of rare syndromes characterized by loss of fat tissue. In some patients, it is genetic, while in others it may be acquired for different pathophysiological, and in some cases unknown, reasons. Generalized lipodystrophy is characterized by widespread loss of fat tissue under the skin, causing a deficit in the hormone leptin, which then leads to multiple metabolic complications.

    Myalept acts similarly to the body’s naturally occurring leptin, meaning that it can help treat certain problems of high triglycerides and high blood sugar levels in people with generalized lipodystrophy  that result from not having enough leptin.

    Gene therapies: the most expensive treatments

    As can be seen from the list, gene therapies have broken all of the records when it comes to the world’s most expensive drugs. And, as the biopharma industry continues to embrace treatments for orphan diseases – illnesses that typically affect a small population – we have seen more and more gene therapy approvals in the last few years, each one seemingly coming with an even more expensive price tag than the last. 

    But it’s worth noting that the extreme rarity of the diseases that gene therapies are used to treat is exactly why the costs are so high. For example, the world’s new most expensive drug, Lenmeldy, treats MLD, which only affects one in every 40,000 individuals in the U.S. This means that, even though they cost so much, selling gene therapies is potentially a risky business.

    Explore other topics: Gene therapy

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