AbbVie dumps Alector's Alzheimer's immunotherapy after phase 1 review

Alector’s new approach to Alzheimer’s disease has ended the way of many of the old ideas for how to tackle the perennial problem. After going over data including phase 1 results, AbbVie has severed its ties to a potential Alzheimer’s immunotherapy—and the asset has vanished from Alector’s pipeline. 

AbbVie teamed up with Alector in 2017, paying $205 million upfront for exclusive options on two drug candidates. Alector presented phase 1 data on one of the candidates, AL003, in healthy volunteers late last year, providing early evidence that the candidate is well tolerated up to once-monthly intravenous doses of 15 mg/kg and engages the transmembrane receptor CD33 in both blood and central nervous system compartments.

Based on the data, Alector, which is responsible for designing and executing phase 1 and 2 studies, set out plans to move to the next stage of development in the second half of 2022. Doubts about whether AbbVie would come along for the ride arose in May, when Alector said it was reviewing the next steps. 

Now, the review has reached its conclusion with AbbVie terminating the CD33 collaboration rather than waiting until the end of phase 2 to decide whether to exercise its option. Alector has removed AL003 from its pipeline but is still working with AbbVie on the development of the other candidate covered by the 2017 deal, namely the humanized, TREM2-activating monoclonal antibody AL002.

The termination of the CD33 pact deprives Alector of a potential source of revenues. Across both AL002 and AL003, the AbbVie deal was worth up to $985.6 million in option exercise and milestone payments. The paydays are now limited to the fees and milestones tied to AL002.

Early hopes for AL003 centered on its ability to block CD33, also known as Siglec 3. Expressed on the resident macrophages of the central nervous system, CD33 is an immunomodulatory receptor that is thought to have a similar function to the role PD-1 plays on T cells. 

There is now a range of evidence implicating CD33 in Alzheimer’s, from the upregulation of the receptor  on immune cells taken from the brains of patients after death to the strong association between risk of developing the disease and changes in CD33. In cell cultures, high levels of CD33 inhibit the clearance of amyloid beta.

Alector thought targeting CD33 could release the brakes on the neurological immune system, much as drugs such as Merck’s Keytruda unleash other immune cells to attack tumors. The mechanism may offer a new way to treat neurodegenerative conditions such as Alzheimer’s, but hopes have taken a hit with the exit of AbbVie.

Alector told Fierce Biotech that it was unable to provide further details about the reasons for dropping the therapy.

“Although disappointed by the news, we're not completely surprised, given the phase 1 trial had been completed over one year ago, and [Alector] had been public for the past few months in saying that next steps in the program were being reviewed (which we had interpreted with a more cautious tone),” said Mizuho analysts in a July 8 note.

They noted that AL002 is the more advanced of the two collaboration programs, with a phase 2 study having been initiated in January 2021 and a top-line readout expected in 2024.