Gaucher Disease, Type 2

Lilly expects a decision on accelerated approval for donanemab by early 2023. Following Eisai’s successful phase 3 readout of its Alzheimer’s disease treatment lecanemab, the pressure—and optimism—is mounting for top competitor Eli Lilly.  On the company’s third-quarter earnings call Tuesday, executives heralded those results, which found a 27% reduction in clinical decline among treated patients with early Alzheimer’s, as providing additional validation of the amyloid beta hypothesis that’s driven the development of Lilly's own donanemab. “Following donanemab’s TRAILBLAZER-ALZ study, this lecanemab study may further support the benefit of removing amyloid plaques for people with early, symptomatic Alzheimer’s data,” said Lilly’s chief scientific and chief medical officer Dan Skovronsky, M.D., Ph.D. Plaque buildup is the result of the amyloid beta protein misfolding in the gaps between neurons and has been thought to be a biomarker of neurodegeneration.  Similarly to Eisai, Lilly is looking to nab accelerated approval of donanemab first, with executives estimating that a decision could come in early 2023. The company would then apply for full approval following a readout of its ongoing phase 3 trial expected by the middle of next year. While the company is bullish on Lilly's prospects, particularly in light of the lecanemab readout, analysts at SVB Securities put the chance of phase 3 success at 40%.  Nonetheless, with both companies gearing up for commercial launches next year, Lilly’s executives used the quarterly briefing to assure investors of its stake in the market. Anne White, the company’s head of neuroscience, said Lilly’s work in Alzheimer’s over the last 30 years—from diagnostic production to setbacks and successes—has cemented its reputation and commitment.  The Alzheimer's spotlight on this morning's call was not solely focused on donanemab, as hyped as the drug was. Lilly also outlined progress on its next-gen amyloid plaque-targeting monoclonal antibody, remternetug, into a phase 3 trial, with a primary endpoint centered on amyloid clearance. But like donanemab, the program will ultimately expand to assess clinical impact.  “We have a broader phase 3 program that [we’re] initiating as well as looking at the clinical endpoints as done for donanemab, but we're excited about what we're seeing so far with remternetug,” said White. The company is aiming to recruit some 400 patients for the trial with an estimated primary completion date of March 2024.  Looming large over both drugs, however, is how much the Centers for Medicare and Medicaid Services will ultimately reimburse for them. At the beginning of the year, following Biogen’s controversial approval for Aduhelm, CMS proposed only reimbursing amyloid-targeting monoclonal antibodies approved through the accelerated pathway when used in authorized randomized control studies. White says that in light of both donanemab’s phase 2 data and lecanemab’s phase 3 data, it’s time to reconsider.  “So certainly, we would hope that this is resolved before remternetug reads out,” she said. “Obviously, the timeline, though, is not clear.” White added that should donanemab have a positive phase 3 readout, the company will request reconsideration, saying that “we cannot see a reason that CMS will continue to prevent Alzheimer's patients from getting these medicines.” Outside of Alzheimer’s, Lilly disclosed clinical challenges for one of its gene therapies acquired from Prevail Therapeutics. GBA01, formerly known as PR001, logged a $206.5 million impairment charge due to “delays in its clinical development and estimated launch timing,” according to a Lilly spokesperson.  The drug is currently in two phase 2 trials for patients with Parkinson’s disease and Gaucher’s disease type 2, respectively. The spokesperson did not respond when asked whether there were delays in both trials, or just one. Lilly also disclosed that it was tacking on a third trial for the drug, targeting Gaucher’s disease without a specific type. GBA01 is one of only two clinical-stage drugs Lilly acquired when it shelled out more than $1 billion to buy Prevail in 2020. Editor's note: This story was updated to include additional editorial from an earnings call.