NICE nixes Orchard's gene therapy Libmeldy in metachromatic leukodystrophy

The National Institute for Health and Care Excellence (NICE) has released draft guidance in which the UK drug pricing watchdog recommends against NHS use of Orchard Therapeutics' Libmeldy (autologous CD34+ cells encoding the ARSA gene) to treat metachromatic leukodystrophy (MLD). EU regulators granted the stem cell gene therapy a full marketing authorisation for early-onset MLD last December.

Specifically, the EU approval was to treat MLD characterised by biallelic mutations in the ARSA gene in children with late infantile or early juvenile forms, without clinical manifestations of the disease. It is also indicated for children with the early juvenile form of MLD, who exhibit early clinical manifestations, but are still able to walk independently and before the onset of cognitive decline.

'Uncertain' long-term efficacy

The treatment, which is given as a one-time intravenous infusion, involves collecting ex vivo autologous CD34+ haematopoietic stem and progenitor cells from the patient's bone marrow or peripheral blood. These are then transduced with a lentiviral vector, which inserts copies of human ARSA complementary DNA into the genome, producing modified cells that can secrete functional ARSA enzyme.

NICE agreed in its draft document that Libmeldy, also known as OTL-200, improves mobility and cognitive function, and could correct the ARSA enzyme deficiency caused by the disease. However, it said the treatment's long-term efficacy is "uncertain." Moreover, the agency suggested that the quality-adjusted life year (QALY) gains with Libmeldy are also "highly uncertain and [vary] substantially between subgroups." Taking these factors into account, it concluded that "the cost-effectiveness estimates are unlikely to be within what NICE normally considers cost effective."

List price from €2.5 million to €3 million

For European markets, Orchard has estimated a list price in the range of €2.5 million ($3 million) to €3 million ($3.6 million) for a one-time treatment of Libmeldy. The amount "is less than the average 10-year cumulative cost for some chronic or lifelong rare disease treatments, such as certain enzyme replacement therapies, which do not offer the potential for full genetic correction or a potentially positive impact on cognitive outcomes," the company stated in its annual report for last year. In addition, Orchard said it was working with European payment authorities regarding reimbursement and access, adding it was also considering "novel payment approaches, such as annuity payments," as part of the talks.

Meanwhile, NICE acknowledged that MLD is a rare condition with significant unmet need for an effective disease-modifying treatment. "Also, there are benefits beyond direct health benefits that are not captured in the economic analysis," NICE said, "but even taking these factors into account, [Libmeldy] is not recommended." The agency has set a July 30 closing date for comments regarding its evaluation, with a third evaluation committee meeting scheduled later this year on October 6.

Orchard's treatment was awarded a regenerative medicine advanced therapy (RMAT) designation by the FDA for MLD earlier this year. Late last month, Orchard said that following discussions with the FDA, it plans to submit a filing for US approval of the treatment in pre-symptomatic, early-onset MLD in late 2022 or early 2023, using data from existing patients.