CHICAGO New data on Pfizer Inc and Johnson & Johnson's Alzheimer's drug, bapineuzumab, show the treatment reduced underlying markers of the disease in some patients, suggesting the failed medication might work at an earlier stage.
The findings from two large studies, presented at a European neurology meeting in Stockholm on Tuesday, followed the companies' announcement last month that they were scrapping large-scale clinical trials of the drug after it failed to improve memory or thinking skills in patients with mild to moderate Alzheimer's.
Many researchers had expected bapineuzumab to fail this test because they believe that Alzheimer's starts years before memory problems become apparent, and that treatment when patients already have dementia may be too late.
But they have been eagerly awaiting the so-called biomarker results, which measure fluids and tissues in the body, to see if the drug hit its biological targets and therefore, could work at an earlier stage of the disease.
The biomarker results show that bapineuzumab significantly reduced levels of the protein beta amyloid on the brain scans of patients with a gene mutation that increases their risk of Alzheimer's, compared with subjects who were give a placebo.
The drug also significantly reduced the amount of a toxic form of the protein tau in spinal fluid, a sign of brain cell death, compared with patients who were given a placebo.
However, MRI tests showed patients in the treatment and placebo groups had a similar loss of brain volume.
Dr. Reisa Sperling of Harvard Medical School and Brigham and Women's Hospital presented results of a study of patients who carry the ApoE4 gene mutation. She said the findings were not a "home run in biomarkers," but are encouraging.
"I am happy there is evidence that we are having some effect on the disease process in the brain," she said in a telephone interview from Stockholm.
"I am very interested in moving towards a much earlier stage of Alzheimer's disease in which we might be able to impact the biology at a time when we might prevent symptoms."
The results of a second trial of patients who were not carriers of the ApoE4 mutation, presented by Dr. Stephen Salloway of Brown University in Rhode Island, showed no significant improvements, but there was some reduction in a marker of brain cell death at the highest dose. Because the follow-up study only included 39 patients, however, it was likely too small to show much of an effect, Salloway said.
In both trials, a significant number of patients experienced a brain-swelling side effect known as vasogenic edema, and rates of this problem increased as the dose of the drug increased.
In 2009, the highest dose of the drug was dropped from the non-carrier study because of this brain-swelling issue.
Researchers said the lower doses tested in the studies -- 0.5 milligram per kilogram in the ApoE4 carriers and both 0.5 mg/kg and 1.0 mg/kg in the non-carriers -- may explain why the patients failed to see a benefit in memory and thinking skills.
Maria Carrillo of the Alzheimer's Association, who had seen the results, said they suggest the biomarkers were moving in a "positive direction."
Sanford C. Bernstein analyst Tim Anderson said in a note to clients the results "leave open the possibility" that the bapineuzumab may work in earlier stage disease.
Researchers will be comparing these findings to those of Eli Lilly and Co's similar drug, solanezumab. Although the Lilly drug also failed to meet its study's main goals in mild to moderate patients, the company did see a slight benefit when they isolated results for mild patients.
Biomarker results for Lilly's drug are expected to be released on October 8 at a neurology meeting in Boston. Researchers have not yet analyzed pooled data on mild patients in the bapineuzumab studies.
Although Pfizer and J&J discontinued all studies involving the intravenous form of bapineuzumab, they have an ongoing study testing the treatment in a shot form.
Dr. Eric Yuen of J&J said the newer formulation may offer a more smooth exposure to the drug than the IV version, which could help reduce some of the side effects.
Sperling said side effects will play a role in the future of bapineuzumab. "I think it will be important to see whether we will get a better side effect profile that will allow us to dose higher," Sperling said.
Several studies, including one proposed by Sperling, will be testing drugs such as bapineuzumab in patients with normal memories who are likely to develop Alzheimer's, either because they are genetically predisposed to it or because biomarker tests suggest it is already forming.
Salloway, who is also helping to organize a study known as DIAN in patients with an inherited form of the disease, said researchers will examine all available data in order to pick compounds likely to influence the disease process early on.
(Editing by Andre Grenon and Leslie Gevirtz)