New Alzheimer’s treatments are the tip of the iceberg in a long-stymied area of medicine

After years of mounting frustrations in the field of Alzheimer’s treatments, the approval of disease-modifying anti-amyloid drugs like Leqembi from partners Eisai and Biogen is just one step in making a real difference for patients.

That step is nothing short of revolutionary, said Gene Kinney, CEO of Prothena Biosciences, a clinical-stage biotech with a pipeline in neurodegenerative and other protein misfolding diseases. But a common critique of Leqembi’s approval — and its $26,500 annual price tag — is that progress is too incremental.

“In my mind, there is nothing incremental about moving the treatment paradigm from drugs that treat symptoms to drugs that fundamentally delay the underlying biology of this progressive disease,” Kinney argued. The primary outcome of the Leqembi trial showed a 27% slowing in clinical dementia measurement over 18 months and a 37% slowing of decline in functional daily living.

Kinney harkens back to the first drug for HIV — called azidothymidine, or AZT — that was developed in the 1960s and ignited a treatment revolution. Many drugs have since followed in AZT’s footsteps, improving treatment by magnitudes and changing outcomes for patients over time.

“AZT wasn’t the last treatment for HIV because nobody stopped there despite the beneficial impact it had,” Kinney said. “And ultimately, we now commonly think of HIV as a chronically manageable disease, and that’s where we want to move Alzheimer’s — to a place where we improve the benefit and broaden the population to make it a manageable disease long term.”

Beyond new disease-modifying drugs approaching the market, Prothena is also looking at the next stage of Alzheimer’s therapy: disease prevention in early-stage or even non-symptomatic patients.

A preventive approach

Vaccines have worked wonders in infectious disease and are on the cusp of making a difference in cancer. A vaccine for neurologic diseases like Alzheimer’s would be monumental, Kinney said. Prothena’s PRX123, a preventive treatment targeting both amyloid beta and tau proteins in the brain, is in line for an investigational new drug designation from U.S. regulators this year.

In general, there are two approaches to prevention. Secondary prevention would occur in patients already showing biological signs of Alzheimer’s but still without cognitive decline. Primary prevention would give patients without biological signs of the disease an opportunity to avoid it altogether.

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“In my mind, there is nothing incremental about moving the treatment paradigm from drugs that treat symptoms to drugs that fundamentally delay the underlying biology of this progressive disease.”

Gene Kinney

CEO, Prothena Biosciences

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“We think a vaccine could be the correct modality for that approach, much like we use vaccines in other areas of medicine,” Kinney said. “PRX123 is relatively unique [because] it simultaneously targets both the amyloid beta protein, which may be an early cause of the disease, but also the tau protein, which becomes a critical component of the disease in progressing to cognitive and functional deficits.”

Despite the different schools of thought between targeting amyloid beta and tau Kinney believes, like many others in the field, that both are viable approaches. Prothena has two candidates in early clinical trials that tackle each one: PRX012 for amyloid beta and PRX005 for tau.

“Ultimately, the field is getting excited about potentially using combination approaches in the context of disease,” Kinney said. “I think about it as a complex steam engine pushing a boat across the ocean, where amyloid beta is the coal that drives the engine, but there’s so much more going on that there are multiple ways to slow the boat.”

Comparing Alzheimer’s to yet another field of medicine, Kinney says the multimodality approach to cancer can inform drug development as well.

“Much like we see with oncology, if you think about [Merck’s] Keytruda as a foundational asset, you also see combination approaches that improve the efficacy profile,” Kinney said. “And that can mean a better slowing of disease in a patient population or it could mean expanding the patient population who may receive a benefit from those approaches.”

Collaborative efforts