Lenmeldy, First Approved MLD Gene Therapy for Children, Becomes Most Expensive Drug in the US at $4.25 Million

The US Food and Drug Administration (FDA) has awarded approval to Orchard Therapeutics for its gene therapy Lenmeldy (atidarsagene autotemcel) for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD).

Lenmeldy is the first and only FDA-approved gene therapy for children with these types of MLD.

After its approval on Monday, Orchard announced that the wholesale acquisition cost (WAC) for its one-time gene therapy would be $4.25 million. This makes Lenmeldy the most expensive drug in the US, a title previously held by CSL Behring and uniQure’s gene therapy Hemgenix, which was approved in 2022 and is priced at $3.5 million.

Orchard said the steep price “reflects its clinical, economic and societal value,” including the “potential long-term impact treatment may have on overall healthcare utilization, minimization of productivity loss for caregivers and life opportunities for patients.”

The company said the WAC was based on an assessment by the Institute for Clinical and Economic Review (ICER) which determined the health benefit price benchmark (HBPB) for Lenmeldy to be up to $3.94 million, the highest value-based price ever assessed by ICER.

Acknowledging the high cost, Orchard said it is offering innovative outcomes- and value-based agreements to both private and government insurers “to ensure broad, expedient and sustainable reimbursed access.”

It has also set up the Orchard Assist patient services program to provide individualized support throughout the treatment process.

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Japan-based pharmaceutical company Kyowa Kirin acquired Orchard Therapeutics in a $477.6 million deal that was completed earlier this year. Kyowa said it made the deal for the goal of accelerating the delivery of new gene therapies to patients around the globe. The transaction has proven fruitful with the milestone US approval of the gene therapy just a few months later. Orchard is considered a subsidiary of Kyowa Kirin.

MLD is a rare genetic disease affecting the brain and nervous system caused by a deficiency of the enzyme arylsulfatase A (ARSA), which results in the accumulation of sulfatides (fatty substances) in cells. This buildup causes damage to the central and peripheral nervous system, leading to debilitating loss of motor and cognitive function and early death.

Lenmeldy is a one-time, single-dose infusion that involves taking a patient’s hematopoietic (blood) stem cells (HSCs) from the bone marrow, genetically modifying them to include functional copies of the ARSA gene and re-infusing the modified stem cells into the patient. Before receiving Lenmeldy, patients have to receive high-dose chemotherapy to remove cells from the bone marrow in order for them to be replaced by the modified HSCs.

According to the FDA, it is estimated that MLD affects one in every 40,000 individuals in the US. Every year, less than approximately 40 children in the US are born with the condition. MLD has no cure and current treatments mainly involve supportive care and symptom management.

“Lenmeldy is truly a paradigm-shifting medicine and has the potential to stop or slow the progression of this devastating childhood disease with a single treatment, particularly when administered prior to the onset of symptoms,” said Bobby Gaspar, MD, PhD, co-founder and chief executive officer of Orchard Therapeutics in a statement. “We are committed to enabling broad, expedient and sustainable access to this important therapy for eligible patients with early-onset MLD in the US.”

Apart from Lenmeldy (also known as OTL-200), using its HSC gene therapy technology platform, Orchard had two other clinical-stage programs — OTL-203 for the treatment of mucopolysaccharidosis type I Hurler’s syndrome (MPS-IH) and OTL-201 for mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome.

Related: Beqvez Becomes Pfizer’s First Approved Gene Therapy After Nod from Health Canada

Lenmeldy Clinical Data: Longest Follow-Up for a Newly Approved Gene Therapy

Orchard said that with more than 12 years of follow-up in the earliest treated patients (median of 6.76 years), Lenmeldy is launching with “an unprecedented amount of follow-up data … the longest duration of follow-up available at the time of approval for a gene therapy in the US to date.”

Orchard received its first approval for the MLD gene therapy in the EU in December 2020, where the drug’s commercial name is Libmeldy. Following the EU green light, Libmeldy scored a regenerative medicine advanced therapy designation from the FDA that helped it along its path to US approval.

The efficacy and safety of Lenmeldy were evaluated based on data from 37 children in two clinical trials and an expanded access program. Lenmeldy was found to significantly lower the risk of severe motor impairment or death. Specifically, and remarkably, all children with pre-symptomatic late infantile MLD treated with Lenmeldy survived to six years of age, outperforming the 58 percent survival rate in the untreated group. Additionally, treated children showed preserved walking ability and normal cognitive scores, marking a notable improvement over the untreated group.

At five years of age, 71 percent of Lenmeldy-treated children could walk without assistance.  Additionally, 85 percent of treated children had normal language and performance IQ scores, something not reported in untreated children. Children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD also showed slowing of motor and/or cognitive disease.

Lenmeldy’s application received FDA Priority Review, Orphan Drug, Rare Pediatric Disease and Regenerative Medicine Advanced Therapy (RMAT) designations.

Qualified Treatment Centers

Lenmeldy is being made available to eligible patients through a network of qualified treatment centers (QTCs) in key regions throughout the US to minimize the travel burden on patients and their families. Five treatment centers with specialized expertise in transplant and the treatment of neurometabolic diseases, like MLD, are being activated.

The five QTCs will be ready at the launch of the gene therapy, including the M Health Fairview Masonic Children’s Hospital in Minnesota, which is in the final stages of qualification but has already treated several children with MLD on a compassionate use basis. The other treatment centers, also currently undergoing qualification, include Children’s Healthcare of Atlanta, Children’s Hospital of Philadelphia, Texas Children’s Hospital and UCSF Benioff Children’s Hospital San Francisco.

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