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10 of the Most Expensive Drugs in the U.S.

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 1, 2024.

1. Lenmeldy

Lenmeldy (atidarsagene autotemcel) is an autologous hematopoietic stem cell (HSC) gene therapy for the treatment of children with metachromatic leukodystrophy (MLD). Lenmeldy is the first treatment for MLD and has the potential to restore enzymatic function to stop or slow this fatal disease with a single treatment. Lenmeldy will be given at Qualified Treatment Centers in some U.S. states.

The wholesale acquisition cost (WAC) of Lenmeldy will be US$4.25 million according to Orchard Therapeutics, making it currently the most expensive drug in the U.S. Officials at Orchard cite the value of therapy to patients and their families, possible caregiver wage loss, and the potential to lower healthcare utilization.

MLD is a rare and potentially fatal genetic disease of the metabolic system caused by a mutation in the arylsulfatase-A (ARSA) gene. This mutation causes accumulation of sulfatides (a type of fat) that destroy the protective layer of the nerves called the myelin sheath. Patients eventually lose the ability to move, talk, swallow, eat and see. Mortality is estimated at 50% at 5 years for late infantile disease and 44% at 10 years for juvenile patients.

Lenmeldy works by inserting one or more functional copies of the human ARSA gene into the genome of a patient’s own hematopoietic stem cells (HSCs), outside the body, using a lentiviral vector. Cells are then infused back into the patient where they can migrate across the blood-brain barrier into the central nervous system and express the functional enzyme.

Open-label studies looked at data from 37 pediatric patients with early-onset MLD with 12 years of follow-up (median 6.8 years). All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to 58% in the natural history group. At 5 years of age, 71% of treated children were able to walk without assistance. 

The most common adverse reactions (≥10%) include fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver.

2. Hemgenix

Hemgenix (etranacogene dezaparvovec-drlb) is approved to treat hemophilia B, a rare, lifelong bleeding disorder. Given as a single, one-time intravenous (IV) infusion, it's list price of $3.5 million makes it the most expensive drug in the U.S. It allows people living with hemophilia B to produce their own factor IX (a blood clotting factor) and can lower the risk of bleeding with a single dose.

Hemophilia B 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. People with the condition are particularly vulnerable to bleeding in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Typically, patients with hemophilia B have to adhere to strict, expensive, lifelong infusion schedules of factor IX.

Hemgenix is an adeno-associated virus vector-based gene therapy. It works by supplying a noninfectious viral vector (AAV5) 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. 

In the HOPE-B clinical trial, Hemgenix reduced the rate of annual bleeds and 94% of patients discontinued factor IX infusions. Seven to 18 months after Hemgenix, the mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by 54%.

The most commonly reported side effects (incidence ≥5%) with this gene therapy were liver enzyme elevations, headache, elevated blood enzymes, flu-like symptoms, infusion-related reactions, fatigue, nausea and feeling unwell.

3. Elevidys

Elevidys (delandistrogene moxeparvovec-rokl) is approved for the treatment of children aged 4 through 5 years with Duchenne Muscular Dystrophy (DMD) with a confirmed mutation in the DMD gene.

It's given as a one-time, single-dose intravenous (IV) infusion with a $3.2 million price tag. Patients selected for treatment have anti-AAVrh74 total binding antibody titers <1:400. Elevidys should not be used in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.

Duchenne Muscular Dystrophy (DMD) is the most common childhood form of muscular dystrophy and typically occurs in boys. It is an inherited degenerative disease that results in muscle weakness and loss of muscle tissue, which worsens over time. The average life expectancy is about 27 years.

DMD is caused by a dystrophin gene mutation that yields low levels of the dystrophin protein, needed to strengthen muscle fibers. Elevidys was designed to treat the underlying cause of DMD by delivering a gene that codes for a functional shortened dystrophin (called Elevidys micro-dystrophin) into the muscle tissue.

Accelerated approval was based on expression of Elevidys micro-dystrophin observed in patients treated with Elevidys. Continued approval may depend upon further clinical trial results from the Phase 3 EMBARK trial, expected in late 2023.

Warnings include acute serious liver injury, immune-mediated myositis (muscle inflammation) and myocarditis (heart muscle inflammation). Common side effects include vomiting and nausea, elevated liver enzymes or total bilirubin, pyrexia (fever), and thrombocytopenia (low platelet counts).

RelatedWhat are the new drugs for Duchenne muscular dystrophy?

4. Skysona

Skysona (elivaldogene autotemcel or eli-cel) gene therapy was approved as the first treatment to slow the progression of neurologic brain dysfunction in boys 4 to 17 years of age with early, active cerebral adrenoleukodystrophy (CALD).

Skysona is made from the patient’s own stem cells and modified to contain a copy of the gene to make a functional enzyme called ALDP (adrenoleukodystrophy protein). Skysona is given as a single, one-time intravenous (IV) infusion treatment at a cost of $3 million. 

Cerebral adrenoleukodystrophy (CALD) is a rare, inherited and fatal neurodegenerative disease that occurs primarily in young boys (median age of onset 7 years). CALD occurs due to a mutation in the ABCD1 gene which prevents the production of the ALDP enzyme. This prevents the breakdown of very long-chain fatty acids, which results in destruction of the sheath (myelin) that surrounds the nerve. CALD results in loss of ability to communicate, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. Nearly half of patients who do not receive treatment die within 5 years of symptom onset.

In studies, Skysona-treated patients had an estimated 72% likelihood of Major Functional Disability (MFD)- free survival at 24 months from time of first neurologic function score (NFS) ≥ 1, compared to untreated patients who had an estimated 43% likelihood of MFD-free survival.

Skysona carries a Boxed Warning for hematologic malignancies, including life-threatening cases of myelodysplastic syndrome. The most common adverse reactions (≥ 20%) include: mucositis (mouth sores, inflammation), nausea, vomiting, febrile neutropenia (fever with low white blood cell count), and alopecia (hair loss), among others.

5. Zynteglo

Zynteglo (betibeglogene autotemcel or beti-cel) is a lentiviral vector (LVV) gene therapy approved for the treatment of adult or pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions. Zynteglo is made specifically for each patient from their own stem cells and is given as a one-time, single-dose intravenous (IV) infusion at a cost of $2.8 million. 

Beta-thalassemia is a rare, genetic blood disease that can result in severe anemia and lifelong dependence on red blood cell transfusions, a lengthy process that patients typically undergo every 2 to 5 weeks.

Zynteglo works by adding functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells. The gene is added into a patient’s cells outside of the body (ex-vivo), and then infused into the patient. This can result in normal or near normal levels of total hemoglobin and can eliminate the need for regular red blood cell transfusions. 

In studies, 89% (32/36) of evaluable patients achieved transfusion independence, defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average total hemoglobin of at least 9 g/dL. 

Warnings and precautions associated with Zynteglo include delayed platelet engraftment, risk of neutrophil engraftment failure, risk of insertional oncogenesis, and hypersensitivity reactions.

In studies, the most common adverse reactions (≥20%) were: mucositis (inflamed mouth / digestive tract), febrile neutropenia, vomiting, pyrexia (fever), alopecia (hair loss), and epistaxis (nose bleed) among others.

6. Zolgensma

Zolgensma (generic name: onasemnogene abeparvovec-xioi) is a life-saving gene therapy approved to treat Spinal Muscular Atrophy (SMA) in pediatric patients less than 2 years of age. Zolgensma is given a one-time, single-dose, intravenous (IV) infusion therapy with a total cost at approval of $2.125 million. It works by replacing the defective or missing survival motor neuron 1 (SMN1) gene to treat the root cause of SMA and halt disease progression. It is considered potentially curative.

Spinal Muscular Atrophy (SMA) is a rare genetic motor neuron disease that results in problems with breathing, holding up your head, and swallowing. The majority of children with SMA do not survive past early childhood due to an inability to breathe (respiratory failure).

In studies, effectiveness was demonstrated in 36 patients who were between 2 weeks and 8 months of age at study entry. Of 21 patients treated with Zolgensma, there are 19 remaining patients, who range in age from 9.4 to 18.5 months; 13 of these 19 patients are at least 14 months of age. Developmental motor milestones were also met.

Zolgensma labeling carries a Boxed Warning that acute serious liver injury can occur.  In studies, the most common side effects were elevated liver enzymes and vomiting. 

7. Myalept

Myalept (metreleptin for injection) was FDA-approved as a replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital or acquired generalized lipodystrophy. Lipodystrophy can be inherited through the genes or acquired without a known cause.

Lipodystrophy is a rare condition that affects how the body stores and use fat. Fat may build in places where it should not be, such as the blood and organs. Patients with generalized lipodystrophy often develop severe insulin resistance, diabetes, or high levels of triglycerides (hypertriglyceridemia) that can lead to pancreas inflammation.

Myalept is given as a subcutaneous (under the skin) injection once a day and patients can be taught to self-administer the medicine at home. One 11.3 mg vial runs about $6,188 and doses are weight-based. As one example, a patient might use about 18 vials per month, therefore annual drug cost might exceed $1.3 million.

In clinical trials, Myalept led to reductions in HbA1c (a measure of blood sugar control), fasting glucose, and triglycerides. Due to the risk of neutralizing antibodies and lymphoma, Myalept is only available through the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program.

8. Danyelza

Danyelza (naxitamab-gqgk) 40 mg/10 mL is approved to treat adults and children 1 year of age and older with high-risk neuroblastoma in the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), who have demonstrated a partial response, minor response, or stable disease to prior therapy.It is used in patients that have progressed or had an incomplete response to therapy.

Neuroblastoma is a solid tumor that occurs in the nervous system, outside of the brain, most often in infants and young children. These tumor cells can spread (metastasize) to other sites in the body, such as the bone or bone marrow. Some tumors can be treated, but the majority are very aggressive. 

Danyelza is classified as a GD2-binding monoclonal antibody immunotherapy. It works by attaching to tumor cells and sends a signal to the immune system to kill the cancer.

Danyelza is administered to patients 3 times in one week (of each 28-day cycle) as an intravenous (IV) infusion in an outpatient setting, liker a clinic. Treatment cycles are repeated every 4 weeks until complete or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. 

In 2 studies, patients had an overall response rate (partial response + complete response rate) of 34% and 45%. In these studies, 23% and 34% of patients continued to respond to treatment without the tumor growing or spreading for at least 6 months after initial response. Treatment may be stopped due to disease progression or intolerable side effects. Your doctor will decide how long to treat you with this medicine. 

Each 40mg/10 mL (4 mg/mL) single vial costs about $24,300. The length of treatment depends on response, and dosing is weight based, so it's hard to estimate an exact cost. As an example, if patient used 48 vials of medicine the drug cost would run about $1.2 million annually. Danyelza is also used in combination with GM-CSF to help your body to produce certain blood cells that help fight the cancer and help prevent infections, which adds to the cost of therapy.

Danyelza contains a boxed warning for serious infusion-related reactions and neurotoxicity. Common side effects include infusion-related reaction, pain, fast heart rate, vomiting, cough, nausea, diarrhea, among others. 

9. Zokinvy

Zokinvy (lonafarnib) is used for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and processing-deficient Progeroid Laminopathies (PL). Zokinvy is indicated in adult and pediatric patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above. Zokinvy offers a survival benefit for patients with genetic premature aging diseases

Progeria and Progeroid Laminopathies are very rare genetic premature aging diseases that accelerate death in young patients. Untreated children with Progeria die of heart disease at an average age of 14.5 years of age. Approximately 20 children and young adults are known to have the disease in the U.S.

Zokinvy is a disease-modifying agent that blocks the accumulation of defective, farnesylated proteins. Data was derived from two open-label clinical trials in 62 patients. In patients with Progeria, Zokinvy reduced the incidence of mortality by 60% and increased average survival time by 2.5 years.

Zokinvy dosing is based on body surface area (BSA) and is given as a capsule twice daily with morning and evening meals. The cost for Zokinvy is about $26,000 for 30 of the 50 mg capsules and $39,000 for 30 of the 75 mg capsules. As an example, in a patient taking four 50-mg capsules per day, the cost would be roughly $1.2 million per year.

The most commonly reported side effects were mild or moderate gastrointestinal events (vomiting, diarrhea, nausea).

10. Kimmtrak

In Jan. 2022 the FDA approved Kimmtrak (tebentafusp-tebn), an immunotherapy for the treatment of HLA-A*02:01-positive adult patients with uveal melanoma that has spread to other parts of the body or can’t be removed with surgery.

Uveal melanoma is a rare and aggressive form of eye cancer. Up to 50% of people with uveal melanoma will eventually develop cancer in other parts of their bodies.

Kimmtrak works by attaching to the HLA-A*02:01 / gp100 complex, a lineage antigen often expressed in uveal melanoma cancer cells. Immunotherapy works along with your own immune system to help your body fight cancer. Kimmtrak was the first T-cell receptor (TCR) treatment to receive FDA approval.

The recommended dose is 20 mcg by intravenous (IV) infusion on Day 1, then 30 mcg IV on Day 8, 68 mcg IV on Day 15, and 68 mcg IV once every week thereafter. The cost for Kimmtrak intravenous solution (100 mcg/0.5 mL) is around $20,764, or an annual cost of around $1.1 million. Patients are typically treated until unacceptable toxicity occurs or there is disease progression.

In Phase 3 studies, overall survival (OS) of Kimmtrak was compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated . Kimmtrak demonstrated statistically and clinically meaningful results with a median overall survival of almost 22 months compared to 16 months for other treatments (a median 6 month overall survival benefit of 6 months). Median means 50% of patients had a survival benefit longer than 6 months, and 50% less than 6 months.

Kimmtrak carries a Boxed Warning for Cytokine Release Syndrome (CRS), which may be serious or life threatening. The most common side effects (occurring in ≥ 30% of patients) are CRS, rash, fever, itching, fatigue, nausea, chills, abdominal pain, edema, low blood pressure, dry skin, headache and vomiting.

Note: Drug costs listed are estimates and are subject to change at any time. This list is not all inclusive. Prices may vary based on length of treatment, doses, manufacturer financial assistance or other factors. 


Further information

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