Aiming to deliver blockbuster sales of its Alzheimer’s-disease-fighting antibody Leqembi in its 2027 fiscal year, Eisai has cleared a key regulatory hurdle in its quest to grow the medicine's reach.
The FDA has approved a once-weekly subcutaneous maintenance dose of the drug in an autoinjector, dubbed Leqembi IQLIK, according to a joint press release from the Japanese pharma and its commercialization partner Biogen.
In line with the label of the drug’s intravenously infused formulation, Leqembi IQLIK is cleared for use in Alzheimer’s patients with mild cognitive impairment or mild dementia. Patients may switch to the new subcutaneous maintenance dose after 18 months of intravenous (IV) initiation treatment every two weeks, or they can opt to stick with infusions every four weeks for maintenance therapy, Eisai said in its release.
IQLIK’s approval could be a “game changer” in Alzheimer’s treatment, Katsuya Haruna, senior group officer and executive vice president of U.S. business operations at Eisai, said in an interview with Fierce Pharma, noting that the 15-second injection is now the first and only amyloid therapy that can be administered at home.
The do-it-yourself benefit could be especially meaningful for patients in rural areas who may have trouble reaching infusion centers, and it could free up more infusion capacity at those centers in parallel, he added.
The autoinjector’s convenience edge should also make maintenance dosing simpler for Alzheimer’s patients and those caring for them, which is crucial to keeping patients “in the earliest stages of the disease,” when Leqembi’s potential to slow progression is most potent, Eisai’s chief clinical officer, Lynn Kramer, M.D., said during the interview.
The FDA based its approval on results from subcutaneous sub-studies of Eisai’s phase 3 Clarity AD open-label extension trial. Those studies showed that patients with early Alzheimer’s maintained clinical and biomarker benefits on par with IV dosing after switching to weekly Leqembi IQLIK injections after 18 months on the initiation dose, Eisai said in its approval announcement.
In terms of safety, none of the patients who received the IQLIK maintenance dose experienced any local or systemic injection-related side effects. Only 1% of patients experienced systemic reactions—like headache, fever or fatigue—on Leqembi IQLIK, while rates reached up to 26% among the cohort that received the infused drug, Eisai said.
Rates of amyloid-related imaging abnormalities (ARIA)—a potentially severe classwide side effect among anti-amyloid drugs—were comparable between the IQLIK and infusion arms in Eisai’s trials and “similar to background rates of ARIA in patients without treatment,” according to the company. Most ARIA in Leqembi patients occurs within the first six months of IV initiation treatment, Eisai noted.
On the topic of ARIA, Eisai’s Leqembi IQLIK nod has dovetailed with a new FDA recommendation that Leqembi patients receive additional, earlier MRI monitoring prior to their third infusion. The move is designed to better identify people displaying ARIA with edema (ARIA-E), which can cause swelling or fluid buildup in the brain. The previous prescribing information recommended MRIs before the 5th, 7th and 14th infusions, according to an FDA communique.
The maintenance equation
A green light for subcutaneous Leqembi and evolutions in testing for Alzheimer’s diagnosis are key milestones on Eisai’s quest to achieve 250 billion Japanese yen to 280 billion yen ($1.7 billion to $1.9 billion) in Leqembi sales in its 2027 fiscal year, which wraps up in March 2028.
While Leqembi sales in the U.S. have taken off slower than analysts initially expected, “we are going in the right direction,” Haruna said of Leqembi’s growth. More and more patients are starting on the drug, and sales momentum continues to pick up, he explained.
Leqembi revenue grew 20% sequentially in the most recent quarter, reaching total sales of 23.1 billion yen (roughly $157 million), Haruna pointed out. The drug generated 9.1 billion yen (nearly $62 million) in the U.S. during that period.
That increased pace is due, at least in part, to a dramatic rise in Alzheimer’s testing rates over the past year, Haruna said. Plus, demand for the drug is climbing as the long-term benefits of Leqembi become more apparent and patients are once again able to perform tasks, such as using the bathroom by themselves, that they struggled with before treatment, the executive added.
Continued maintenance dosing for a drug like Leqembi is essential as recognition of Alzheimer’s as a chronic disease increases, Kramer stressed.
The disease “starts many years before there’s a plaque buildup in the brain,” which Eisai believes is due to protofibrils—peptide assemblies that gather in the brain and eventually become amyloid plaque—he explained.
Leqembi is approved based on its ability to both rapidly clear amyloid plaque and continuously clear protofibrils. For comparison, Eli Lilly’s approved Alzheimer’s competitor Kisunla only targets plaque and can be discontinued once a patient’s amyloid build-up is cleared.
Once plaque has been cleared, however, protofibrils continue to intrude and can lead to more amyloid amassing in the brain over time, causing Alzheimer’s symptoms to return, Kramer noted.
Eisai has been building out its protofibril thesis and recently presented data at the Alzheimer's Association International Conference linking Leqembi’s protofibril-targeting mechanism of action to sustained benefits in patients taking the drug over four years.
Regarding IQLIK’s launch, doctors are already “well aware” of Leqembi’s subcutaneous presentation, and customers have been clamoring for the easier dosing format, too, Haruna noted. The company has said it plans to make IQLIK available in the U.S. on Oct. 6.
In a pricing statement, Eisai noted that it will set its wholesale acquisition cost (WAC) for IQLIK at $375 per autoinjector, which doesn’t account for rebates and discounts through insurance.
That equates to a list price of $19,500 per year, an Eisai representative noted over email. For comparison, the annual WAC for Leqembi IV maintenance dosing is approximately $13,316, though the final price varies because the intravenous version uses weight-based dosing.
“Eisai’s pricing reflects the balance between enabling broad patient access, supporting long-term sustainability of the healthcare system, and recognizing the demonstrated societal value of subcutaneous administration,” the company said.
With an FDA nod for its subcutaneous maintenance dose in hand, Eisai will waste no time pursuing a similar approval for its 500-mg subcutaneous initiation dose, Kramer said during the interview.
The company plans to file that application with the FDA next week. Eisai expects to receive a breakthrough therapy tag on its next subcutaneous initiation dose application and is hopeful it will receive priority review and a rolling submission framework, which would trigger a roughly six-month review timeline for the subcutaneous initiation dose, Kramer said.