Aducanumab-avwa

Eli Lilly will be submitting the data on the modified dosing regime of Kisunla to global regulators. Image credit: Tada Images / Shutterstock. A modified dosing regimen with Eli Lilly’s Alzheimer’s drug Kisunla (donanemab) has shown a reduction in amyloid-related imaging abnormalities with oedema/effusion (ARIA-E). Lilly announced data for the TRAILBLAZER-ALZ 6 Phase IIIb trial (NCT05738486) yesterday (29 October) at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) Conference in Madrid, Spain. Kisunla is approved in the US , Japan , the UK and other countries. Lilly is discussing the results of this study with global regulators, with the intent to submit for a potential label update for Kisunla. ARIA-E was one of the big talking points of the US Food and Drug Administration (FDA) Advisory Committee (AdCom) meeting as they debated whether the drug should be approved in the US . The TRAILBLAZER-6 trial evaluated the impact of different dosing regimens of Kisunla on the rates of ARIA-E and amyloid clearance in adults with early symptomatic Alzheimer’s disease. There were four arms in the study, one on the standard dosing and three on modified dosing schedules, but all patients received the same volume of the drug throughout the study. One of the modified dosing arms met the primary endpoint of the proportion of participants with any occurrence of ARIA-E by week 24. The only difference between the modified titration and the standard dosing regimen is the shift of one vial from the first infusion to the third infusion. Patients on the standard dosing regimen received two vials (700mg) of Kisunla for the first three infusions, then four vials (1,400mg). See Also: Novartis’ Scemblix gains FDA approval for leukaemia GSK to acquire Chimagen’s CMG1A46 for autoimmune disease Meanwhile, patients on the modified titration received one vial (350mg) for the first infusion, two vials for the second infusion, three vials (1,050mg) for the third infusion, and four vials per infusion thereafter. The incidence of ARIA-E was 14% in patients receiving the modified titration compared with 24% for those receiving the standard dosing regimen, a 41% lower relative risk. The largest ARIA-E reduction with the modified titration was seen in apolipoprotein E (APOE4) homozygotes, carriers of a known genetic risk factor for developing Alzheimer’s disease. In these patients, 19% had ARIA-E on the modified titration as compared to 57% on the standard dosing regimen, resulting in a 67% lower relative risk. Patients on the modified titration of Kisunla only saw a slight difference in reduction of amyloid plaque and P-tau217 67% from baseline compared to 69% for patients on the standard dosing regimen. The drug acts by removing amyloid plaques and P-tau217 from the brain to slow the progression of the disease, both of which are believed to be causes of Alzheimer’s disease. Eli Lilly neuroscience R&D group vice president Dr Mark Mintun said: “Lilly is confident in the benefits of Kisunla’s currently approved dosing regimen and is excited that these results reveal a path to potentially improving Kisunla’s profile by reducing the risk of ARIA-E. The modified titration could offer continued convenience of once-monthly dosing and limited duration treatment while also reducing ARIA-E and maintaining similar amyloid plaque removal.” Despite Kisunla’s UK approval, the drug will not be available on the National Health Service (NHS) as it does not represent “good value” . There is only one other drug on the market with the same mechanism of action, Leqembi (lecanemab) , developed by Eisai and Biogen. A third drug on the market, Eisai and Biogen’s Aduhelm (aducanemab) received accelerated approval , but following issues with brain swelling, the companies pulled the candidate off the market and focused efforts just on Leqembi.

iStock/ Evgeny Gromov The acquisition of Aliada Therapeutics gives AbbVie access to a Phase I anti-amyloid antibody as well as the biotech’s novel platform engineered for efficient blood-brain barrier transport. With several early- to mid-stage assets already in its pipeline , AbbVie took an even deeper dive into the Alzheimer’s space Monday with the acquisition of Aliada Therapeutics. At the heart of the deal—which will see AbbVie pay $1.4 billion in cash to acquire the Boston-based biotech—is ALIA-1758, an anti-amyloid antibody currently in Phase I development for Alzheimer’s disease. This is the same drug class that recently burst onto the scene in the form of Biogen/Eisai’s Leqembi and Eli Lilly’s Kisunla , both approved in the last two years as the first disease-modifying therapies for Alzheimer’s. The acquisition also gives AbbVie access to Aliada’s Modular Delivery (MODEL) platform, which is “engineered for both efficient BBB (blood-brain barrier) transport and downstream therapeutic functionality,” according to the company’s website . In an investor note Monday, BMO Capital Markets analyst Evan David Seigerman said BMO views the deal “as positive for AbbVie shares, albeit risky given the indication and stage of development, expanding into a therapeutic area it knows well and continuing to bolster its pipeline for long term growth beyond recent commercial success with Skyrizi & Rinvoq.” Stifel analysts added in an investor note that the deal “seemingly offers a vote of confidence in amyloid, just as sentiment in the space is reaching an all-time low.” ALIA-1758 targets pyroglutamate amyloid beta, which is similar to the epitope targeted by Eli Lilly’s Kisunla , John Dunlop, chief scientific officer at Aliada, previously told BioSpace . The novel technology targets transferrin and CD98 receptors TfR and CD98, which are highly expressed in the brain’s endothelial cells, and uses the transferrin receptor to drive its cargo to cells and force degradation and elimination of the plaques, Dunlop explained. By transporting the cargo in this way, a higher concentration of the antibodies is delivered across the blood-brain barrier to drive therapeutic benefit. “Many promising CNS-targeted therapies fail to reach late-stage trials due to their inability to cross the blood-brain barrier,” Michael Ryan, chief medical officer at Aliada, said in a statement Monday, adding that the company is “excited about AbbVie’s commitment to bringing ALIA-1758 to patients with Alzheimer’s disease.” AbbVie already has a considerable presence in the Alzheimer’s R&D space, and Seigerman noted that Aliada’s assets are potentially complementary to a number of Alzheimer’s assets that AbbVie already has in development. The company’s pipeline includes ABBV-916, an anti-AβpE3 antibody; ABBV-552, an SV2A modulator being evaluated to target nerve terminals to enhance synaptic efficiency; and AL002, an antibody being developed in partnership with Alector Therapeutics. “Neuroscience is one of our key growth areas and we are committed to driving innovation in this field to address critical unmet needs for patients living with seriously debilitating neurological diseases such as Alzheimer’s disease,” Roopal Thakkar, EVP of research and development and chief scientific officer at AbbVie, said in a statement . Aliada’s platform “strengthens our R&D capabilities to accelerate the development of next-generation therapies for neurological disorders and other diseases where enhanced delivery of therapeutics into the CNS is beneficial.” The deal is expected to close in the fourth quarter of 2024, subject to regulatory approvals and other customary closing conditions.