Scale model of Children's Hospital Colorado in Aurora, a top center of research on neuromuscular diseases. (Photo courtesy of the Muscular Dystrophy Association)
Scale model of Children’s Hospital Colorado, a top center of research on neuromuscular diseases. (Photo courtesy of MDA)

AURORA, Colorado—Those who believe gene therapy has the potential to treat, if not cure, Duchenne muscular dystrophy (DMD) are anxiously awaiting federal regulators’ action on Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001).

The US Food and Drug Administration (FDA) is expected to rule on the therapy’s biologics license application on May 29, 2023. Hospitals and specialized clinics must be prepared to cope with an expected surge of demand for this treatment, said pediatric surgeon Julie Parsons, MD, of Children’s Hospital Colorado in Aurora, a suburb of Denver.

SRP-9001 has “amazing potential,” Dr. Parsons told Rare Disease Advisor in a recent interview here.

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Dr. Parsons, who’s also a professor of clinical pediatrics and neurology, has been associated with Children’s Hospital Colorado since 1976, when she started there as a physician’s assistant.

In the ensuing 47 years, she has become a national expert on spinal muscular atrophy (SMA), and on administering the 3 breakthrough drugs neurologists now widely use to treat it: Biogen’s nusinersen (Spinraza®), approved by the FDA in December 2016; the Novartis gene therapy onasemnogene abeparvovec-xioi (Zolgensma®), which won approval in May 2019; and Genentech’s oral medication risdiplam (Evrysdi®), approved in August 2020.

“I think it will be a little bit different than the therapies that we have for SMA,” she said of SRP-9001. “SMA is really a monogenic disorder. Duchenne and the dystrophinopathies are more complex disorders. We can’t deliver the full gene as we can with SMA, but we have the potential to prolong the lives of men and boys with Duchenne, and to certainly improve the quality of life for these guys.”

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Even so, Dr. Parsons is not necessarily optimistic that giving a gene therapy like SRP-9001 early enough will prevent the symptoms of Duchenne from ever developing, as appears to be the case with onasemnogene abeparvovec.

“It’ll be a little bit different with the dystrophinopathies, where it’s not as urgent,” she said. “Although we certainly want to treat as many patients as we can—and as quickly as we can—there’s no emergency of losing motor neuron cells and developing significant weakness within days to hours of being born.”

She cautioned that with Duchenne, “the results may not be quite as dramatic” as what’s been seen in babies given onasemnogene abeparvovec for SMA.

Creating a ‘Complex Drug Program’ for New Gene Therapies

Children’s Hospital Colorado is one of a number of sites in the US and Europe where SRP-9001 has been undergoing double-blinded, placebo-controlled clinical trials in boys aged 4-7 years. The hospital covers a huge swath of the western United States encompassing Colorado and 6 nearby, rural states: Kansas, Montana, Nebraska, New Mexico, South Dakota, and Wyoming. 

Julie Parsons, MD, a pediatric neurologist at Children’s Hospital Colorado in suburban Denver. (Photo by Larry Luxner)

“Patients sometimes drive 12 hours from Montana in a blizzard just to come here,” she said.  “Our multidisciplinary clinic started in 1989 for that very reason. Patients really can’t be driving back and forth and taking time off of work for several days to come in for an appointment.”

Dr. Parsons, who’s also codirector of the Muscular Dystrophy Association (MDA) neuromuscular clinic here, said her team covers virtually all aspects of care, including physical therapy, occupational therapy, rehabilitation, pulmonary, genetics, social work, nutrition, and neurology.

“We have a lot of different subspecialists who see those patients and meet their particular needs. Of course, all of this was funded as an MDA clinic, which has been fantastic for us,” she said.

In preparing to treat patients with SMA, Dr. Parsons created a “complex drugs program” (CDP) that consists of an operations coordinator—who manages administrative tasks such as authorization, insurance approval, and scheduling—as well as 2 nurses who handle medical issues.

“They see the patients as they come in to be treated, and help with the hospital delivery of these agents. That’s worked really well for the patients, as well as for us in the program,” she said. “When we look at a new drug to be vetted into the CDP, it has to meet certain criteria: it has to be high‑cost, high‑risk, and delivered to a population of complex patients. For instance, boys with [Duchenne] certainly would meet those criteria.”

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Once a particular drug is vetted, Dr. Parsons assigns a “knowledge leader,” which in this case will be Susan Apkon, MD, a professor of physical medicine and rehabilitation and the principal investigator for Children’s Colorado in the current Sarepta trial.

At the moment, 38 children and teens with SMA are receiving nusinersen injections at Children’s Colorado. They come in every 3 months for a spinal tap. “After the initial load, they come quarterly, for life,” she said.

In addition, 17 children have been given onasemnogene abeparvovec. Patients with SMA and their families may choose which treatment to use, but the hospital tries to treat all patients with SMA as emergencies, Dr. Parsons said.

Lessons From the Specialized SMA Treatment

Many of the lessons learned with SMA can be applied to Duchenne if and when Sarepta’s gene therapy receives the FDA’s blessing, Dr. Parsons said.

To that end, Dr. Parsons has formed a “gene team” that comprises experts in hepatology, immunology, cardiology, neurology, pulmonology, infectious disease, nephrology, hematology, oncology, physiatry, ethics, and government affairs. This team has met once a month for more than 3 years in preparation for new gene therapies.

This is extremely important, she said, because SMA gene therapy has already caused liver failure and thrombotic microangiopathy in certain cases.

“How do we prepare medically to deal with these kids when they get sick—because they get sick fast. I had the indistinct honor of being the neurologist whose first kid treated with Zolgensma went into liver failure,” she said. “Fortunately, this patient was treated aggressively, and is now 4 years old and doing just fine.”

Dr. Parsons added: “We know that the immune system is excited when we give this agent, and that some immune issues may come up that can cause significant problems. Internationally, we’ve had 2 deaths of SMA patients who were treated with Zolgensma in the last 6 months. That is very sobering.”

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Figuring out who is going to pay for gene therapy for the thousands of patients with Duchenne who may qualify for SRP-9001 is also a huge challenge. Its likely retail price of around $4 million is nearly twice that of $2.1 million onasemnogene abeparvovec—and insurance companies are already reluctant to reimburse for such costly therapies.

If SRP-9001 wins approval for treating DMD, Dr. Parsons said, her hospital expects to receive 20-25 patients with the disease, depending on what ages and specific genetic conditions the FDA authorizes the therapy for.

“If it gets approved, then we will be hopefully one of the specified sites for treatment. We also hope to be a referral center for other states that are not able to deliver the drug,” she said.