But in a perplexing twist, the drug did show a significant benefit in about 15 percent of patients in the trial who were not taking other standard Alzheimer’s drugs, according to the findings released on Wednesday at the Alzheimer’s Association International Conference in Toronto.
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A phase 3 study of LMTX (TauRx Therapeutics), an investigational tau aggregation inhibitor, has failed to meet its coprimary endpoints in patients with mild or moderate Alzheimer’s disease (AD).
Claude Wischik, cofounder of Singapore-based TauRx and a professor of geriatric psychiatry at Aberdeen University, said in that so-called “monotherapy” group, the drug reduced the rate of decline in cognitive and functional skills by 85 percent. He called this result “unexpected” but “hugely encouraging” and said it jibed with initial results the company has seen from a second large clinical trial, which are to be published later this year. No difference between LMTX and control on cognitive and behavioral changes falls below FDA’s regulatory requirements for approval of an Alzheimer’s drug, Hartley added.
LMTX attacks the tangles of protein (tau) found in dying and dead nerve cells in patients’ brains, a different approach from other Alzheimer’s drugs now on the market.
A number of other companies are developing tau-targeted drugs, including Johnson & Johnson, Roche Holding AG, Bristol- Myers Squibb Co. and AbbVie Inc.
Most Alzheimer’s research is based on the theory that clumps of a different protein known as beta amyloid cause the disease, although no one has yet developed a drug effective enough to validate this hypothesis.
Biogen (BIIB) and Eli Lilly (LLY) are still trying. Another is the beta-amyloid protein fragments that accumulate and form plaques between nerve cells in the brain.
“As a practising clinician I see Alzheimer’s patients, their families and care-givers every day, and continually share their desperate need for a truly therapeutic product as today we only have symptomatic treatments available to us”. There are no approved medicines capable of slowing or reversing the progression of the disease.
The trial involved 891 people who already had mild or moderate symptoms of Alzheimer’s disease.
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The ADAS-cog decline analysis produced significant treatment effects of -6.3 (P 0.0001) and -5.8 (P 0.0001) units after patients received 75 mg twice daily (BID) or 125 mg BID of LMTX as monotherapy, respectively, while the ADCS-ADL decline analysis produced significant treatment effects of 6.5 (P = 0.0013) and 6.9 (P = 0.0007) after treatment with 75 mg BID or 125 mg BID of LMTX as monotherapy, respectively. Both doctors and patients were blinded to their respective treatments. He pointed to a separate analysis of brain scans that showed a statistically significant reduction in the rate of brain shrinkage among the monotherapy patients who benefited, suggesting the drug slowed brain atrophy. Wischik says the most likely explanation is that these other drugs help to clear toxic material out of the brain, so may also clear away LMTX too. The safety of the drug was “acceptable” and comparable to the safety profile of other Alzheimer’s disease drugs in clinical trials.
