Experts Warn Against Interrupting Pompe Treatment During Pandemic

At a recent webinar, experts cautioned that it could be dangerous for people with Pompe disease to stop treatment due to the COVID-19 pandemic.

The disease that would come to be called COVID-19 was first reported in the U.S. more than a year ago. As it spread across the world there have been more than 117 million reported cases, and nearly 2.6 million deaths, according to the World Health Organization. While recently-approved vaccines offer hope to return to normalcy, the experts cautioned that the pandemic is still very much ongoing, and is likely to continue disrupting life for some time yet.

“Even though it might seem so to those of us who have access to vaccines, we’re not nearly at the end of this,” said Maxwell Damian, MD, a consultant neurologist at Cambridge University Hospitals, U.K.

In the webinar, “Impact of Covid 19 on rare neuromuscular diseases: Lessons from Pompe Disease,” hosted by Sanofi Genzyme, Damian offered an overview of the challenges the pandemic has placed on people with neuromuscular diseases, and on systems that care for them. Broadly, pandemic-related concerns often have made it difficult for people to receive, or continue to receive, the appropriate care.

Damian said that healthcare systems have tried to adapt to these changing pressures; for example, there has been an increased reliance on telehealth, when healthcare visits are done virtually (by phone or video calls). Still, as the pandemic continues to unfold, people with Pompe disease may have to make decisions about whether to interrupt treatment due to COVID-19-related safety concerns.

Dangers of interrupting treatment

During the webinar, Benedikt Schoser, MD, a professor of neurology at Ludwig-Maximilians-University of Munich, Germany, provided an overview of data about interrupting treatment in people with Pompe disease. He focused on enzyme replacement therapy (ERT), the standard treatment modality for those with Pompe. ERT for Pompe involves therapeutic administration of the acid alpha-glucosidase enzyme, which is lacking in people with Pompe.

First, Schoser highlighted data from a collection of studies done in Switzerland where, due to national insurance issues, seven people with late-onset Pompe disease (LOPD) had their ERT treatment interrupted for varying lengths of time (ranging from three months to nearly five years).

For these individuals, pausing treatment led to worsening of lung function and physical function. When ERT resumed, some recovered to functional levels near where they had been prior to stopping treatment.

“These data suggest that the long-term interruption of ERT may lead to a deterioration in clinically meaningful parameters and quality of life,” Schoser said.

Schoser then shared data from 12 LOPD patients treated in Germany, whose ERT treatment was interrupted in March-April last year due to COVID-19.

These findings, which were published recently in the Journal of Neurology, also generally indicated that interrupting ERT treatment led to worse lung and physical functioning. Seven of the 12 patients reported a total of 14 adverse side effects related to interrupting treatment. Two of these events were severe, and the most common were reduced muscle function and breathing difficulty.

The big takeaway from these findings is that “the interruption of ERT, in the long term but also in the short-term, should be kept as short as possible,” Schoser said.

Minimizing treatment interruptions may be particularly important for children with classic infantile-onset Pompe disease.

“It’s really the classic infantile-onset [Pompe disease] you would try to avoid any cessation [of treatment], because there it’s really a life-threatening situation,” Schoser said. “We would never try to stop [treatment] if it’s not an absolute emergency.”

According to Schoser, long-term ERT interruption generally had a more severe impact on people who already had more severe disease in the Swiss studies. However, he said the shorter-term German study did not find similar results, so the relationship between disease severity and the effect of interrupting treatment remains unclear.

Schoser also acknowledged that, in some cases, it may be necessary to briefly delay treatments for reasons like travel, but noted that such delays should be kept as short as feasible. The experts also said that there is no data to make a clear recommendation as to whether ERT should be interrupted during pregnancy.

Strategies to avoid interrupting treatment

Damian said that, in many places, systems are already in place to make it easier for people with Pompe disease to safely access treatments. For example, in many hospitals, areas where COVID-19 patients are treated are separate from other locations, so that non-COVID patients can receive treatment with a comparatively low risk of exposure to the virus.

Another possible way to make Pompe treatments more safely accessible is to expand the use of home infusion — where a medication is administered at home, rather than at a hospital. Notably, home infusion is recommended only  for people who already have an established history of ERT treatment.

“Hopefully, it won’t be necessary to interrupt treatment in hospital, but of course, home infusions are even better,” Damian said.

The availability of home infusions, however, differs greatly based on location. For example, Schoser said that home infusions have been a standard practice in the U.K. and the Netherlands. Other countries, such as Italy and Spain, have passed emergency measures allowing home infusion during the pandemic.

“In many other European countries, [home infusion is] not available or even not allowed,” Schoser said.

He highlighted a need to make home infusion more available, particularly in Europe, saying “it could be something that we need really to work up, that we have this in hand for, unfortunately, the next pandemic situation.”

COVID-19 vaccines recommended

Both Schoser and Damian also highlighted that the currently-available COVID-19 vaccines are considered safe and effective for use in people with Pompe disease.

“There basically isn’t any neuromuscular disease where vaccine is contraindicated [recommended against], full stop now, at this point,” Damian said. “And I don’t think there is a particular concern around patients on ERT. So, vaccination is still felt to be beneficial in all neuromuscular disorders.”

Schoser added that there is “no line of evidence” that any of the available vaccines would be unsafe or ineffective in people with Pompe disease.

COVID-19 vaccines — as the one made by Johnson & Johnson that was recently granted emergency use authorization in the U.S. — may utilize a modified adeno-associated virus (AAV). AAV also is used as a vector for gene therapies already approved or in development, including for Pompe disease.

Because of this similarity, there have been some concerns that people who receive the vaccines may not be eligible for future gene therapies. However, Schoser pointed out that the specific type of AAV vector used in vaccines is quite different from the ones used in gene therapies.

Therefore, receiving any of the available COVID-19 vaccines is “not an exclusion” for receiving a future gene therapy, Schoser said.