The big drug news from the annual Alzheimer’s Association meeting this week involved companies that have found silver linings in otherwise gloomy data—a recurrent theme in Alzheimer’s clinical work. The trials are expensive, so companies are loathe to write them off completely, and the social urgency of finding new treatments encourages data analysis that is generally frowned upon.
“Companies are reluctant to give up drugs in which they have invested a lot,” said Jeffrey Cummings, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health, who attended the meeting in Toronto.
More than five million Americans have Alzheimer’s disease, most of them over 65. As the population ages, the Alzheimer’s burden will grow. The Alzheimer’s Association estimates nearly 14 million Americans will have the disease in 2050. But no treatments other than a pair of old cognition-boosting drugs have been approved to treat Alzheimer’s, in 1996 and 2003, and the past decade has seen numerous high-profile failures.
The human toll of the disease is compounded by the financial toll. Caring for people with dementia costs three times as much, on average, as caring for people of the same age and health profile minus the dementia, according to a 2010 report by the Alzheimer Study Group.
The biggest news this week came from the first-ever Phase 3 test of a pharmaceutical approach different than what’s been used in several failed Alzheimer’s studies. Yet the results for the experimental drug, LMTX, developed by a privately held Singapore company called TauRx Therapeutics, were also negative. LMTX failed to meet its main goal, but TauRx pointed to a silver lining in the data. Company officials said 15 percent of patients in the 891-patient study—those who were taking LMTX by itself, not with other drugs—seemed to benefit and suffered less tell-tale brain atrophy than in patients who were taking LMTX and standard Alzheimer’s drugs. The announcement prompted a few breathless news headlines that were immediately slammed by clinical science watchdogs.
The practice of “subgroup analysis,” as it is known, can be valuable in a disease like Alzheimer’s, where researchers have only scraped the surface of biological insight. Scientists and doctors know what the ravages of Alzheimer’s look like in the brain, but “we don’t understand well at all the multiple causes and susceptibilities” beneath the disease, said Peter Snyder, a neurologist and chief scientific officer at Lifespan Health System in Providence, RI. “In the struggle to figure this out, all these subgroup analyses are performed.”
But it’s one thing to glean insights from such analyses; another to use them to form clinical opinions or make investment decisions. To be useful, slicing up the patient groups within a study has to be planned in advance—not cobbled together after the fact—and thoroughly explained, said Rachelle Doody, director of the Alzheimer’s Disease and Memory Disorders Center at the Baylor College of Medicine in Houston.
TauRx noted in its announcement that its analysis was indeed pre-planned. But Doody called the results “uninterpretable” because of a lack of information. “And they have certainly overstated their results,” she said. Part of the criticism stems from how TauRx compared the patient subgroups with those taking a placebo.
In an interview with Forbes, TauRx cofounder Claude Wischik said that a second Phase 3 study of LMTX has wrapped up, as well, with similar results. Those data will be released later this year, and the company could take both data sets to regulators to ask for approval.
LMTX is meant to work by reducing buildup of an aberrant form of the protein tau, which creates “tangles” in neurons of the brains of Alzheimer’s patients. A second aberrant protein, beta amyloid, is the focus of most Alzheimer’s drug R&D, and for many years researchers have debated which of the two proteins should be attacked, and by what means, in the fight against Alzheimer’s. TauRx’s drug is the first anti-tau treatment to reach late-stage trials. The practice of finding hints of positive data among larger negative results often smacks of drug-company desperation.
“There are many potential subgroups [such as] age, gender, severity, genotype,” said the Cleveland Clinic’s Cummings. “If you do enough analyses you will find a responsive subgroup by chance.”
In Alzheimer’s, major drug programs have moved ahead after their owners re-examined bad news. The biggest example is Indianapolis-based Eli Lilly’s Phase 3 trial of the drug solanezumab. As Lilly (NYSE: LLY) reported in 2012, solanezumab failed to improve the condition of people with mild to moderate Alzheimer’s disease in studies called Expedition 1 and 2. But Lilly saw rays of hope among … Next Page »