Upstaza to be available at low or no cost for eligible patients in England

Treatment is first disease-modifying therapy for AADC deficiency available through NHS

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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England’s National Institute for Health and Care Excellence (NICE) has recommended that the one-time gene therapy Upstaza (eladocagene exuparvovec) be provided at low or no cost to patients, ages 18 months and older, with severe aromatic l-amino acid decarboxylase (AADC) deficiency.

The favorable decision from NICE’s final draft guidance makes Upstaza the first disease-modifying treatment for AADC deficiency added to the list of medications available through U.K.’s National Health Service (NHS), a public health program funded by taxpayers.

The decision comes about four months after the PTC Therapeutics treatment was approved in the U.K. for the same indication. Upstaza is also approved in the European Union, as well as Iceland, Norway, and Liechtenstein, and PTC plans to file a regulatory application in the U.S. this year.

“The NHS is continually adopting cutting-edge treatments that push the boundaries of medical science and this latest gene therapy demonstrates this once again, providing a first treatment option for children with an incredibly rare condition,” John Stewart, national director for specialized commissioning and interim commercial medicines director at NHS England, said in a press release.

AADC deficiency is caused by genetic mutations in the DDC gene that result in reduced activity of the AADC enzyme needed for producing critical brain signaling chemicals, namely dopamine and serotonin.

Consequently, most patients have significant neurological symptoms. About 80% are considered severely affected, fail to meet major developmental milestones and remain fully dependent on caregivers for their entire lives.

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Upstaza led to motor, cognitive improvements

Only about 120 cases of the ultra-rare disease have been reported worldwide and it’s estimated to affect about 10 children in the U.K., a small number of whom may be eligible for Upstaza.

Formerly known as PTC-AADC, Upstaza provides a healthy version of the DDC gene when infused directly into the brain. It’s the first approved treatment to target the underlying cause of AADC deficiency and the first approved gene therapy to be delivered directly into the brain.

Clinical trial data showed Upstaza led to improvements in motor and cognitive function in children with AADC deficiency for more than five years following treatment. Some children reached important motor milestones like walking without help or running freely.

NICE issues recommendations that dictate which therapies will be listed under the NHS and what patient groups will be eligible to receive them at no or low cost through the public health program.

The decision is based on an analysis of a treatment’s potential benefits and its cost-effectiveness. Upstaza was considered under a Highly Specialized Technologies program, which has a higher threshold for cost-effectiveness.

“The committee heard from patient experts about how the lives of children with AADC deficiency are severely impacted and shortened,” said Helen Knight, director of health technology assessment at NICE. “They also heard about the substantial effect it has on the quality of life of the person with the condition and their family and carers.”

Knight said the committee agreed Upstaza had “transformative benefits” that in some cases were “clearly life changing.”

According to the guidelines, these results  remain “uncertain because the studies are small and provide limited long-term data and limited information about nonmotor outcomes.”

Upstaza’s cost-effectiveness was assessed also on the result of negotiations with PTC to define its final price to NHS England. The confidential deal, which reflects the uncertainty of the therapy’s long-term effects, “has enabled the committee to recommend it as good value for the NHS and taxpayers,” Knight said. While the negotiated price wasn’t disclosed, Upstaza’s list price is around £3 million (about $3.7 million) for its single dose.

NICE’s recommendation supports routine access for severely affected patients.

“If a patient has AADC deficiency and the doctor responsible for their care thinks that [Upstaza] is the right treatment, it should be available for use,” the guidelines state.

NICE expects to publish its final guidance April 19.