Drug development trends often move in waves that eventually come crashing onto the shores of the FDA. This year, a number of key decisions involving neurological biomarkers, an RSV vaccine and more have kept the FDA’s every move in the news.
And although cancer is usually king in pharma, the oncology space is so far having a ho-hum year for approvals, according to Sara LaFever, executive director at Citeline.
Here’s more on the three key trends impacting FDA approvals so far this year.
Despite the Aduhelm hoopla, biomarkers are still all the rage
Last year, controversy plagued Biogen’s Alzheimer’s drug, Aduhelm, which FDA officials approved using the agency’s accelerated approval program. The decision, and to a lesser extent the subsequent approval of Eisai's Leqembi, drew fire because the approvals were based on biomarker data, specifically a decrease in amyloid beta plaque in the brain, without proof that the drugs helped patients. Subsequent changes in billing coverage were enough to sideline Aduhelm, and questions about the FDA process resulted in a leadership shakeup. But ultimately the tumult hasn’t deterred FDA officials from using the same pathway to approve several other neurological drugs this year.
In April, FDA officials used the accelerated approval pathway to greenlight another Biogen drug, Qalsody (toferson), for a rare type of amyotrophic lateral sclerosis (ALS) that affects less than an estimated 500 people in the U.S., according to the FDA. The condition is linked to a mutation in the superoxide dismutase 1 (SOD1) gene.
“The FDA is being a lot more flexible in neurology in general, with all of the approvals coming through."
Executive director, Citeline
“ALS is kind of a hot space in general, but this was an accelerated approval that was based off of biomarkers, which is interesting, because it's not something that's been done before in the ALS space,” LaFever said.
In a phase 3 trial, the drug succeeded in reducing levels of plasma neurofilament light chain (NfL) in cerebrospinal fluid. But it ultimately failed to meet the trial’s primary endpoint — slowing disease progression. The decision to approve the drug was nonetheless celebrated by the ALS Association as a ray of hope for this universally fatal disease.
Other accelerated approvals for neurological conditions in 2023 include Daybue (trofinetide), the first approved treatment for Rhett Syndrome, a rare inherited neurological disorder. In February, the FDA also approved Skyclarys (omaveloxolone), another first for Friedreich’s ataxia, a rare degenerative disease affecting the nervous system, LaFever said.
“The FDA is being a lot more flexible in neurology in general, with all of the approvals coming through,” LaFever said.
This is likely the case because there hasn't been a lot of movement in this space in the past decade, she said. There is also a high unmet need for many of these neurological diseases, which are often life-threatening or debilitating.
New vaccine options
While the FDA has given some drugs a little more wiggle room, its generosity only goes so far. A few candidates — particularly those that will be rolled out to larger patient populations — have received more scrutiny, LaFever said.
Last Wednesday, the FDA approved Arexvy, the first vaccine for RSV for adults over age 60. RSV can be serious in high-risk people such as older adults and infants. It, along with a rival candidate from Pfizer PF-06928316 or RSVpreF, have had a long road to approval.
Arexvy seemed to produce a more favorable response than the Pfizer drug, according to members attending a February meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee, but the advisory committee voted to approve both drugs for efficacy and safety.
Still, FDA advisors raised concerns about adverse events related to Pfizer’s vaccine, including a life-threatening case of Guillain-Barre syndrome, a rare neurological condition. Pfizer said it would be willing to conduct an additional post-approval safety study if needed.
Despite the issues raised, it’s likely the Pfizer vaccine is still on track for a May approval. Other RSV vaccines in the works include Moderna’s late-stage mRNA candidate for older adults. Pfizer is also hoping to gain approval for an RSV vaccine that would be given during pregnancy to protect infants after birth.
A slow start for oncology
While the FDA has generated a handful of news-worthy approvals this year, the oncology space has been uncharacteristically quiet.
“Oncology, so far this year hasn’t been that hot, which is kind of surprising. There haven’t been that many approvals,” LaFever said.
There also don’t appear to be as many head-turning drugs coming through.
“We're not seeing more things of interest in oncology so far, at least in the first half of this year,” she said. But stay tuned, she added — the bulk of approvals typically occur in the fourth quarter.