LY-3002813

Donanemab

In this underserved market, anti-Aβ MAbs lecanemab and donanemab are poised to follow on the heels of the U.S. FDA’s landmark accelerated approval of ADUHELM for the treatment of Alzheimer’s disease (AD). Lecanemab and donanemab could offer differentiated clinical profiles, which may be bolstered by phase 3 results that are expected to be reported beginning in late 2022.

About donanemab

  1. Eli Lilly and Company
  2. Anti-Aβ N3pG MAb
  3. IV infusion every 4 weeks for the treatment of MCI due to AD and mild AD
  4. ~38m people with AD globally
  5. 30% expected increase in total prevalent cases of early AD in the G7 markets by 2029 due to aging population

Why is it a drug to watch?

Clinical trial data suggest that sufficient exposure to optimal doses of anti-Aβ MAb therapy could be clinically effective in early AD. Phase 3 trial results, expected before a confirmatory post-marketing trial of ADUHELM is complete, could further validate — or refute — the efficacy of agents in the class.

  1. Phase 3 studies (TRAILBLAZER-ALZ-2 and TRAILBLAZER-ALZ-3) are ongoing in patients with early AD and preclinical AD, respectively.
  2. Data from TRAILBLAZER-ALZ-2 are expected in the first half of 2023.
  3. Phase 2 efficacy results showed:
    • a reduction in decline from baseline on the iADRS and other metrics at week 76;
    • rapid, deep reduction in amyloid plaques; and
    • lower risk of ARIA (> 20%) than with ADUHELM (40%).
  4. A small phase 3 trial (TRAILBLAZER-ALZ-4) will compare donanemab with ADUHELM head-to-head to assess superiority of amyloid plaque reduction in early AD patients.
    • Data are expected in the second half of 2022.

Review and approval status

June 2021:
Breakthrough Therapy Designation: U.S. FDA

October 2021:
Rolling BLA submitted to the U.S. FDA based on phase 2 data

Expected launch: 
2022: United States
2025: Europe and Japan

Patents estimated to expire beginning in 2031

How will donanemab impact the market for Alzheimer’s disease?

  1. Until the approval of ADUHELM, symptomatic therapy was the only treatment option for patients with AD.
  2. Acetylcholinesterase inhibitors and memantine, now generic, have been and will continue to be the standard of care across mild, moderate and severe disease.
  3. Other anti–Aβ DMTs are in late-phase development, including gantenerumab (Roche).
  4. Many more drugs from a range of MOAs are in mid- and late-phase trials, with potential for further differentiation (e.g., oral administration) and adjunctive use.
  5. Regulatory success of anti-Aβ MAbs could:
    – infuse more investment dollars into dementia and
    – influence companies’ decisions about which drugs to develop.
  6. Until more definitive clinical data are available to differentiate their efficacy, relative uptake of ADUHELM, donanemab and lecanemab may depend on their respective safety and delivery profiles.

What gaps in treatment does donanemab fill?

The most critical need for patients has long been safe, effective DMTs that slow cognitive and functional decline. Initial uptake of ADUHELM has been slow for a multitude of reasons, limiting the patient benefit. Donanemab could offer improved risk/benefit profiles over ADUHELM, and additional therapies could eventually provide greater patient choice and potentially greater affordability.

What hurdles might it need to overcome to reach blockbuster status?

While blockbuster sales should easily be reached based on population size, market demand and pricing, questions remain amid ongoing controversy about ADUHELM’s approval, pending payer decisions and data readouts. Slow uptake is likely until more data are released and reimbursement clarity is achieved.

$4.52B
Expected sales in 2026
95%
probability of success for
donanemab in the United States.
Source : Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of December 15, 2021  

Drug Timeline & Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rate prediction current as of December 15, 2021

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