Lilly scraps an Alzheimer's drug

Once again, Eli Lilly has suffered a setback trying to find a useful drug to combat Alzheimer’s. Last year, a pair of late-stage trials for an injectable drug called solanezumab failed to meet primary endpoints in patients with mild-to-moderate disease (look here).  The results ended hopes of quickly seeking regulatory approval, although another late-stage trial is now under way in patients with mild symptoms (see this).

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 Now, Lilly has ended a mid-stage trial of yet another medication – a beta-amyloid precursor protein site-cleaving enzyme, or BACE, inhibitor – after finding cases of abnormal liver tests. The move is a disappointment because these oral treatments are thought to hold promise, especially after injectables targeting the beta-amyloid protein, which forms brain plaques thought to be responsible for Alzheimer’s, have sputtered. Besides solanezumab, Pfizer ended such a program (back story).

The Lilly compound, however, never generated significant attention. What has been more closely tracked is a BACE inhibitor being developed by Merck, which recently began a Phase II/III study with patients who suffer from mild-to-moderate Alzheimer’s. In announcing its bet last December, Merck noted this is the first drug with this type of mechanism to advance to this stage of clinical research (back story).

Looking beyond the Lilly failure, “we think the more important question here is what does this mean for Merck’s BACE inhibitor,” writes ISI Group analyst Mark Schoenebaum in a note. “While we suspect on first blush that the read across to Merck’s compound is probably minimal, we acknowledge that we cannot totally rule out the possibility that Merck’s compound will also suffer similar results.”

Indeed, beyond putting an end to what had been a horse race between the two drugmakers, there is now going to be concern about a great unknown – was the safety issue confined to the Lilly compound or might this be a sign that such problems exist with all BACE inhibitors? Sanford Bernstein analyst Tim Anderson suggests there had already been hints about problems with the Lilly drug.

“There had been some rumbling in the drug industry about Lilly’s compound, potentially, having a safety issue, which led them to (choose) a lower dose that could have explained the slightly weaker level of beta-amyloid lowering compared to Merck’s compound,” he writes in an investor note. “We asked Lilly directly about this at one point and they denied knowing any safety issues.”

In its statement, Lilly maintained that the abnormal liver tests seen were not related to “the BACE mechanism” and the drugmaker insists it remains interested in developing BACE inhibitors and will reassess this particular program. The suggestion is that the BACE class, as a whole, is not the issue. If true, that is welcome news for Merck, as well as AstraZeneca, Roche and Takeda Pharmaceuticals (more here).

Indeed, Merck may now have “a solid lead above anyone else,” Anderson continues, noting that results from its Phase II trial, which only examines safety, are due later this year. However, this also means that efficacy will not be known until Phase III studies are completed, which he says will not be out until 2017 or so.