TauRx raised more than $225 million from some unconventional financing sources to back their big pair of Phase III studies for a new drug to treat Alzheimer’s. And they traveled to the Alzheimer’s Association’s conference in Toronto to acknowledge that the first study failed on both endpoints.
But that’s not stopping the company from claiming a success.
TauRx CEO Claude Wischik says that investigators tracked a positive response in a subgroup of patients taking the tau inhibitor LMTX as a monotherapy. And while he concedes he has no firm idea why that group benefited when most patients taking a combination of the drug with standard of care showed absolutely identical responses to the control arm, TauRx switched the endpoints on their second Phase III study — just ahead of the data lock — to the relatively small number of patients on monotherapy. And he says they came up with a positive readout that could pave the way to an approval.
The trial results, claims Wischik, are unprecedented in demonstrating an improvement on cognition and function for Alzheimer’s patients.
“We have hit the primary endpoints,” the CEO tells me. “Whether that will constitute adequate evidence for product approval, we can’t say.”
In the first failed Phase III, Wischik says about 15% of the patients in the study were on monotherapy. In the second, it was 20% of the patients. And while Wischik concedes that he’s basing his claim on an analysis of a subgroup of patients in both Phase IIIs, he goes on to reject the notion that it’s a subgroup analysis. After moving the goal posts in the second study, he’s declaring a touchdown on the primary endpoints for the newly switched focus group of patients.
Unlike several of the most advanced drugs in the clinic for Alzheimer’s focused on amyloid beta, Wischik has been an outspoken supporter of the tau theory, pointing to a toxic cluster found in the brains of many patients with the memory erasing disease. But his tau inhibitor LMTX, in combination with standard therapies, failed to separate out from the rate of decline in cognition and function tracked in the control arm.
The data backed up the company’s contention that tau is a “very promising drug development pathway,” Wischik noted. But he also goes on to say that he doesn’t understand why the monotherapy would work while the combo didn’t.
“It’s a weakness,” says Wischik, but not necessarily a fatal one.
If that confusion is shared by regulators, though, it could well scuttle LMTX’s chances of any near-term approval.
In case after case, where a Phase III has ended in failure on the primary endpoints, the developer has had to go back to the drawing board and either design a new program with back to back studies, or throw in the towel.
In Eli Lilly’s case, that meant taking years and hundreds of millions of dollars to tackle the amyloid beta drug solanezumab again. Lilly also moved the goal posts, though, dropping function as a primary endpoint even though regulators are still insisting on seeing clear evidence of efficacy on cognition and function. Others, like GlaxoSmithKline, have walked away after a failure. In GSK’s case, their drug was picked up for $5 million by Axovant, which designed a new Phase III trial for a clearly defined subgroup. Alzheon is taking much the same strategy.
“They can’t get it approved with this,” says one developer actively engaged in the field.
In addition to being equally puzzled about the hypothesis of why the drug would work in this one subgroup and not the rest, the developer noted that regulators would still insist on a new Phase III program before allowing any drug to be marketed to a mass group of desperate patients.
The gold standard in drug development remains a randomized, controlled prospective Phase III trial, and regulators are unlikely to start compromising on that point now.
Based in Singapore with research facilities in Scotland, TauRx was always the odd duck among the flock of companies tackling Alzheimer’s. Unconventional financing from the Malaysian casino and resort operator Genting Group underscored part of the unique picture, and also raises questions of how the company could go about funding a new pair of Phase III studies with 800 to 900 patients, which could easily cost another $200 million.
TauRx has raised expectations of a possible IPO at some point, as company officials say that the absence of any drug that blunts Alzheimer’s could create an instant market worth $10 billion a year for a pioneer like itself. But there have been plenty of others who tried the same thing, only to be beat back in a decade of R&D efforts that have met with universal defeat in the clinic over the past decade.
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