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During the COVID-19 pandemic in England, treatment with Brineura (cerliponase alfa) was considered “essential” for children with neuronal ceroid lipofuscinosis type 2 (CLN2) – also called late childhood Batten disease.

This resulted in no patient missing a dose of the therapy, which is designed to slow the gradual loss of the ability to walk, according to one study.

However, supportive therapy services were largely compromised during the pandemic, and information about COVID-19 vulnerability, protection and testing was somewhat confusing for families. According to these families, the loss of additional therapies resulted in a decline in function and abilities in children with CLN2, although improvements were noted once services were resumed.

These are the results of a new study assessing the effects of the COVID-19 pandemic on the availability of Brineura in the UK. The study involved half of children who received low-cost or free Brineura through the country’s National Health Service (NHS) at the end of 2020.

“Our qualitative survey of families of children with CLN2 disease describes the marked impacts of the pandemic on access to support services and family well-being,” the researchers wrote.

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The study, “Impact of the COVID-19 pandemic on access to managed access agreement to cerliponase alfa in England for CLN2 treatmentwas published in the Orphanet Journal of Rare Diseases.

CLN2 disease, also known as late infant Batten disease, is caused by lower than normal levels of the enzyme tripeptidyl peptidase 1 (TPP1), which leads to seizures and a rapid decline in cognitive functions, language, motor and visual skills in children. children. Symptoms usually appear between 2 and 4 years of age.

BioMarin Pharmaceutical’s Brineura in 2017 became the first – and currently the only – approved treatment targeting the underlying cause of CLN2 disease in the United States and Europe.

It became available to children in England on a limited basis in 2019 via the NHS.

An enzyme replacement therapy (ERT), Brineura works by delivering the missing TTP1 enzyme directly into the cerebrospinal fluid via a surgically implanted access device under the scalp. Cerebrospinal fluid is the fluid that surrounds the brain and spinal cord.

Data from previous clinical trials showed that the therapy, given for four and a half hours every two weeks, slowed disease progression, particularly motor and language decline, in children with CLN2 disease.

In England, where an estimated five to six children are diagnosed with the disease each year, the therapy is now available to eligible CLN2 patients under a five-year Managed Access Agreement (MAA). After the five-year period, health authorities will review real-world data and update their guidance to indicate whether the therapy should be recommended for routine use on the NHS.

To continue to receive Brineura under this MA, patients must attend infusion appointments every two weeks and undergo clinical assessments every six months.

As the COVID-19 pandemic has disrupted health services around the world, including in England, the Batten Disease Family Association (BDFA), a UK charity, and Rare Disease Research Partners assessed the impact of the pandemic on access to Brineura in the country.

At the time of the study, this access was limited to a single specialist centre, the Great Ormond Street Hospital (GOSH), in London. Notably, administration of Brineura is being set up at Manchester Children’s Hospital to ease travel pressure on families and make it easier for patients to access therapy.

The families of 11 of the 21 CLN2 patients enrolled at MAA at the time were included in the study, which also involved the two healthcare professionals responsible for providing therapy at GOSH.

In-depth, semi-structured, separate telephone interviews were conducted by members of the BDFA advocacy team in late 2020, between November 9 and December 21. All interviews were recorded and transcribed, and the data collected remained anonymous.

The children included were aged 4.2 to 18.7 years and had an average age of 8.9 years. They had been receiving Brineura for an average of 23.1 months (almost two years) and up to 76 months (about six years). Patients had been enrolled in AAM for an average of 7.1 months and up to one year.

Families lived on average 210 km or about 130 miles from GOSH, with distances ranging from 7 to 398 km (4.3 to 247.3 miles).

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Analyzes of the interview data showed that Brineura treatment through the MAA was designated as an essential service by the GOSH and that this service continued “as usual; but with additional safety precautions in place,” as reported by medical professionals.

This is “a commendable achievement given reports of widespread disruptions in the care of children with rare diseases, including the administration of ERT,” the researchers wrote.

With the support of “highly motivated families” who “considered the benefits of treatment outweighed the potential risk”, GOSH’s decision to continue Brineura treatment despite COVID-19 restrictions meant that no child missed the scheduled doses, the researchers said.

Despite extreme anxiety about travel, hospital visits and overnight stays in patient hotels, these families felt reassured by information from healthcare professionals – and evidence of safety measures put in place by the hospital, as well as their own COVID-19-related additional precautions.

Notably, although all of the regular clinical assessments required by the MAA were not performed, children could continue treatment under the special conditions of national health emergencies, such as the pandemic.

However, families reported that support services – physiotherapy and chiropractic, massage and speech and language therapies – were largely compromised. This added additional stress and made them worry about the potential deterioration of their children’s physical and cognitive status.

According to families interviewed, their children’s function and abilities actually declined without this additional support, although improvements were noted once services resumed.

While the actual, long-term impact of discontinuing support services for these children remains to be determined, these services “should be considered ‘essential’ for those who rely on them to maintain their physical health, to ensure patients do not deteriorate,” the researchers wrote.

“Patient and caregiver support is also essential to help maintain the physical and mental health of patients and caregivers,” they added.

Another key challenge for these families was to “understand the vulnerability of their children with CLN2 disease” to COVID-19, which makes them uncertain “to protect themselves or isolate themselves, especially when they have children. of school age or continued to work”, the authors. wrote.

This was due to conflicting reports in the media and general government advice on shielding and eligibility for government and NHS support.

Families also reported some confusion over guidance around COVID-19 testing: when it was needed, who should be tested, and how to access testing. These issues were likely resolved with the implementation of widespread COVID-19 testing in England in late 2020, the researchers noted.

These findings “will help understand the additional pressures on families during lockdown and will inform discussions with the National Health Service (NHS) and government agencies about future provision during the recurrence of the pandemic or similar situations in the future. “wrote the investigators.

Based on this information, the team recommended that the risk and vulnerability of specific patient populations be determined as soon as possible and by healthcare professionals experienced in caring for these patients.

In addition, “counseling for children with CLN2 disease should be specific and tailored, taking into account the family unit”, and “supportive therapies should be considered essential alongside [Brineura] treatment,” the authors wrote.

If support services are to be discontinued, “parents need support and guidance to help children at home, to mitigate the potential deterioration of their condition”, they added.