Experts Share Insights on Deciding Treatment in Changing Landscape
Doctors need to know options so patients can make informed decisions: panel
Doctors need to be well-educated about options in the evolving treatment landscape to help patients with spinal muscular atrophy (SMA) make informed decisions, say neurologists in a panel discussion.
The panel of four neurologists with experience in treating SMA patients was convened by Biogen, which markets Spinraza (nusinersen), the first disease-modifying therapy to be widely approved for SMA. Spinraza is administered via injection into the spine every four months; it works to boost levels of the SMN protein whose deficit causes SMA.
Since 2016 when Spinraza was approved, the landscape of SMA has changed, with two other therapies for SMA also gaining approval: Zolgensma (onasemnogene abeparvovec-xioi), a one-time gene therapy sold by Novartis, and Evrysdi (risdiplam), a daily oral medicine marketed by Roche. Like Spinraza, Zolgensma and Evrysdi both work by increasing SMN levels. Zolgensma is approved in the U.S. only for patients 2 years or younger.
Although clinical trials have established the efficacy of all three treatments, there is minimal trial data that directly compares the medicines, nor is there solid data on switching from one medicine to the other or using multiple in combination.
To help fill in this knowledge gap, Biogen convened the panel of neurologists to share their clinical experiences. Each neurologist has been treating SMA patients for 13 to 20 years, including those who switched between therapies.
The group met in mid-2021 to discuss their experiences, and the main take-aways were shared in a study, “Experience and Perspectives in the US on the Evolving Treatment Landscape in Spinal Muscular Atrophy,” published in the International Journal of General Medicine.
“In the absence of randomized, controlled clinical trial data that address changing or combining therapies, real-world experiences in the clinical setting can serve to inform clinicians with regard to the evolving treatment dynamics in care decisions,” the neurologists wrote.
Neurologists offer their insights based on clinical experience and opinions
The team stressed that the paper is based only on their opinions and experience, and it “should not be considered as any form of treatment guidelines, recommendations, or standards of care.”
Since all approved SMA therapies can help to prevent disease progression, but are less effective for restoring lost function, the scientists noted the importance of starting treatment early, especially for newly diagnosed infants who have not shown symptoms yet. They said that, in their experience, families of young SMA children usually opt for treatment either with Spinraza because it’s been in use the longest, or with Zolgensma because it is a one-time treatment.
The panel said it’s important for clinicians to have conversations with caregivers about realistic expectations of treatment — the goal is usually to prevent worsening motor function and help preserve breathing ability.
One feature of the current SMA treatment landscape, the panel said, is that final decisions about starting or switching treatments are usually made by the patient (or by parents or caregivers in the case of young children). Because of this, the experts underscored the importance of clinicians being educated about treatment options, and able to present information in a balanced manner so patients or caregivers can make well-informed choices.
“The panelists highlighted the importance of the physician in presenting all treatment options in a comprehensive, fair, and balanced manner, explaining the known attributes and potential differentiating features of each therapy,” they wrote.
Convenience is often a major factor in treatment decisions, but “the interpretation of ‘convenience’ may differ for each patient,” the panel said. For example, some patients prefer Evrysdi because it can be taken by mouth, whereas others prefer Spinraza because it doesn’t require daily dosing.
The panelists reported anecdotal discussions that Spinraza might be more effective for some patients and Evrysdi for others, perhaps because of pharmacological differences, though this notion “is only a hypothesis, and further research will be needed before any conclusions can be drawn.”
Safety is also a factor in these decisions, with the panel noting that animal studies showing Evrysdi may cause irregularities in sperm development have raised concerns in families of young male patients considering the therapy.
Although patients often express concerns about insurance coverage, “most patients who have wanted to change therapy have been able to do so,” said the neurologists, who’ve also seen “generally good coverage of treatment changes for patients in government insurance programs.” However, while changing therapies is generally covered, combination treatments are often not.
The panel concluded by highlighting the need for more research, especially into the potential use of combination therapies and efforts to maximize early diagnosis and treatment.
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