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U.S. Food and Drug Administration Issues Complete Response Letter for Accelerated Approval of Donanemab Eli Lilly and Company (NYSE: LLY) today announced the U.S. Food and Drug Administration (FDA) has issued a complete response letter for the...

Key Takeaway: Eli Lilly announced that the FDA issued a complete response letter for the accelerated approval of donanemab, a treatment for early symptomatic Alzheimer's disease due to insufficient data on patient exposure. Despite this setback, the Phase 3 TRAILBLAZER-ALZ 2 trial remains ongoing, with data expected in Q2 2023 to support a traditional approval application. Lilly is committed to collaborating with the FDA to expedite the availability of this treatment for patients.

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POSITIVE FACTORS

  • No other deficiencies were identified in the application.
  • Phase 3 clinical trial data is on track for mid-year 2023.
  • Lilly continues to work with the FDA for potential treatment availability.

CONCERNS & RISKS

  • FDA issued a complete response letter due to insufficient patient exposure data.
  • Fewer than 100 patients received the required 12 months of treatment.
  • The approval process is delayed pending more patient safety data.

Full Press Release Details

Accelerated approval application was based on Phase 2 trial showing amyloid plaque lowering
Complete response letter based on limited number of patients with 12-month drug exposure data in the accelerated approval submission; no other deficiencies were identified
Definitive Phase 3 readout and submission for traditional approval remain on track for mid-year 2023
INDIANAPOLIS , Jan. 19, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY ) today announced the U.S. Food and Drug Administration (FDA) has issued a complete response letter for the accelerated approval submission of donanemab for the treatment of early symptomatic Alzheimer's disease due to the limited number of patients with at least 12 months of drug exposure data provided in the submission . No other deficiencies in the application were noted.
The confirmatory Phase 3 TRAILBLAZER-ALZ 2 trial remains ongoing, with topline data read-out expected in Q2 2023, and will form the basis of donanemab's application for traditional approval shortly thereafter. Lilly will continue to work with the FDA to evaluate the fastest pathway to make this potential treatment option widely available to patients.
In the complete response letter to the accelerated approval application , the FDA specifically requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab. Donanemab's specificity to target deposited amyloid plaque informed the unique clinical trial design of TRAILBLAZER-ALZ, which allowed patients to complete their course of treatment when they reached a predefined level of amyloid plaque clearance. While the trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as 6 months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab . The FDA indicated that the data to meet the exposure expectation would likely need to include the unblinded controlled safety data from TRAILBLAZER-ALZ 2 upon completion.
The safety profile of donanemab was initially reported from the TRAILBLAZER-ALZ trial in the New England Journal of Medicine (Mintun et al, NEJM 2021) 1 . The s afety profile of donanemab has remained consistent since our accelerated approval submission.
This action does not result in a change to Lilly's 2023 financial guidance.
About Alzheimer's Disease Alzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases 1 . There are currently over 55 million people living with dementia around the world, with numbers expected to increase to nearly 139 million by 2050 2 . Over 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3.2 seconds and a significant increase in the caregiving burden placed on society and families. In the U.S. alone, there was an increase of nearly 10 million new caregivers from 2015 to 2020 3 . The current annual societal and economic cost of dementia is estimated at $1.3 trillion , an amount that is expected to double by 2030 unless we find a way to slow the disease 2 .
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about donanemab as a potential treatment for people with early symptomatic Alzheimer's disease, and reflects Lilly's current beliefs and expectations. However, as with any such undertaking, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study findings to date, that donanemab will prove to be a safe and effective treatment, or that donanemab will receive regulatory approval. For further discussion of these and other risks and uncertainties, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
SOURCE Eli Lilly and Company

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Frequently Asked Questions

What prompted the complete response letter from the FDA?

The FDA issued a complete response letter due to insufficient patient data with 12-month drug exposure.

How many patients were required to support the accelerated approval?

The FDA requested data from at least 100 patients treated for a minimum of 12 months.

What is the status of the Phase 3 TRAILBLAZER-ALZ 2 trial?

The Phase 3 trial is ongoing, with topline data expected in Q2 2023.

What aspect of donanemab was highlighted in the trial design?

The trial specifically designed to target amyloid plaque clearance influenced its unique structure.

What additional data might be needed for traditional approval?

Unblinded controlled safety data from the completed TRAILBLAZER-ALZ 2 trial may be required.

Last updated: Jan 19, 2023