Dive Brief:

• Roche’s experimental Alzheimer’s disease drug trontinemab showed “best-in-class” potential based on its ability to quickly clear clumps of amyloid protein from the brains of patients enrolled in a small clinical trial, the company said Monday.
• A majority of patients receiving the highest dose of the drug, which is specially designed to penetrate brain tissue, saw their amyloid levels drop below detectable levels after 12 weeks, Roche executives said in an investor presentation on the pharmaceutical giant’s neurology pipeline.
• Though from a small trial, the findings position Roche’s drug as a potential threat to Alzheimer’s medicines Biogen and Eisai, as well as Eli Lilly, have already brought to market or soon could. The drug’s early results make it “worth watching” as a future competitor, wrote RBC Capital Markets analyst Brian Abrahams, in a note to investors.   

Dive Insight:

Like several of its peers, Roche is still plugging away at Alzheimer’s research despite multiple setbacks.

The clinical disappointments of its drugs gantenerumab and crenezumab were part of a run of Alzheimer’s study failures that led many researchers to question whether removing amyloid plaques would actually help patients with the disease. But faith in that so-called amyloid hypothesis has been renewed by the performance in testing of Biogen and Eisai’s Leqembi, as well as Lilly’s donanemab. And now Roche, in its presentation Monday, pointed to a drug it hopes can compete with them.

Leqembi and donanemab have shown an ability to slow the disease’s decline, for instance. But the effects on Alzheimer’s progression are modest and come with side effects, most notably a type of brain swelling called ARIA. And insurers are still hesitant to cover their high costs. A treatment with a more limited duration could reduce those costs, as well as limit side effect risks. 

Roche is positioning trontinemab as that kind of medicine. It uses a type of delivery technology that’s meant to more easily deliver medicines to the brain. Roche is currently testing it in an early-stage trial aimed at uncovering the best dose to use in further testing.

So far, the highest dose tested has been evaluated in just eight people, and Roche only has results through 12 weeks of treatment. It’s unclear whether the findings Roche has seen will be replicated in larger tests, or what type of impact the drug will have on the disease’s trajectory. 

Nonetheless, five of the patients in that group saw their amyloid load drop to undetectable levels, more quickly than what’s been seen in testing of Biogen and Lilly’s medicines. 

“Patients are becoming amyloid negative at this early stage, so it’s really quite a remarkable result,” said Azad Bonni, Roche’s global head of neuroscience and rare disease research, in the presentation.

Additionally, only two cases of ARIA were detected across all four doses evaluated in a total of 49 study participants. Bonni noted, however, that study investigators will need to continue monitoring for future cases given the short study follow-up.  

There’s also the possibility, given its fast plaque clearance, that Roche might consider taking patients off treatment once their amyloid is no longer detectable. Asked by analysts about that possibility, Paulo Fontoura, global head of neuroscience clinical development, said “it’s too early to say” whether reducing or stopping treatment will “lead to the same clinical benefits.”

“That opens up a lot of clinical questions which are not answered yet,” Fontoura said. “What I think it does open up as a possibility is less frequent dosing.”

The potential of the drug to become a monthly infusion with “robust plaque lowering and lower ARIA remains” a possibility, wrote RBC’s Abrahams, and “something we believe will be worth watching” as a potential long-term competitor in Alzheimer’s.”

Still, that outcome is likely a long way away. Roche is currently expanding trontinemab’s early-stage trial and hoping to get a couple hundred patients dosed before determining its next steps, Bonni said.