When the pharmaceutical company Eli Lilly in Indianapolis last week announced a major change his trial monitored closely for drug solanezumab Alzheimer's, some of the Community industry and the development of scientific medicine cried foul. To critics, the company's decision to eliminate changes in daily ability of an individual to function as a first measure of the effectiveness of solanezumab and focus only on a cognitive test appeared to be a last attempt to keep a drug doomed to fail his third trial. Lilly shares fell nearly 5%, apparently reflecting that feeling
Foul play :. Lilly is trying to cheat on the study midstream # Alzheimer obviously because the medicine will not work. https://t.co/dnp7C9mWYz
- Allen Frances (@AllenFrancesMD) March 16, 2016
largely lost in the line "chat", however, is that the movement Lilly reflects a growing scientific consensus on how the early stages of the progression of Alzheimer's disease, said Dennis Selkoe, a neurologist at Brigham and Women's hospital in Boston, who is not involved in the Lilly trial. "From the standpoint of a neurologist who has seen hundreds of patients, [Lilly’s decision] clinical sense," he said.
Solanezumab is an antibody designed to bind to and promote the clearance of β -. amyloid protein that forms plaques around neurons of people with Alzheimer's disease Not everyone agrees that these plaques are the cause of the disease, a concept called amyloid hypothesis, which Selkoe is a developer, but important fight is the basis of almost all current efforts in the development of Alzheimer drugs. by helping to destroy plaques in people with early stages of the disease Alzheimer's, Lilly hopes solanezumab may slow the progression of the disease.
A major challenge of these trials is how to measure the benefits of the drug, said Selkoe. Although people with early Alzheimer's disease may show impairment and problems with attention and memory of light concentration, they can often follow recipes, make a cup of coffee, or drive a car, said Selkoe. These capabilities are unlikely to change the course of a clinical trial of 18 months, and any medications to improve the daily functions is unlikely to show a difference from placebo, he said.
Regulatory bodies such as the US Food and Drug Administration (FDA) have always required and still officially stipulate that the Alzheimer drugs show efficacy in two cognitive tests and functional measures. Recognizing that functional measures might not be appropriate at an early or mild stage of the disease, however, the FDA and other agencies have begun to soften their initial standards for drugs to prevent, rather than reverse the pathology and symptoms of Alzheimer's disease, said Selkoe.
In two previous trials of solanezumab, called EXPEDITION and EXPEDITION II, Lilly used both a cognitive test and a functional measure to monitor the response of people with Alzheimer's disease in both mild and moderate . Both trials failed to show significant benefits compared to placebo in both measures. Combing through the second trial data, however, Lilly noticed that participants with mild Alzheimer's disease seemed to do better than the controls in the cognitive part of the test, said Eric Siemers, a neurologist employed by Lilly.
This led to Lilly's current play a billion dollars on a study of about 2,100 people with only mild Alzheimer's disease, which ends in October. The last-minute decision to abandon the functional measure in this third trial, EXPEDITION III, was not based on any insight into the current test data, as some have suggested, Siemers said investigators are still blind to which participants received the drug and who received a placebo.
instead, the change reflects the functional evaluation of belated recognition certainly, there is no well validated for mild Alzheimer's patients, according Siemers. "As we've done more analysis, and talked to more people in the field, we got to the point where we did not know what functional measurement is the best for this group," he said. To fill this gap, the company is still collecting operational data using two separate evaluations, and hopes to see if either is better detect subtle changes, Siemers said.
Scott Small, a neurologist at Columbia University who is not involved in all clinical trials of Alzheimer's drugs, says he finds that it is a "reasonable" explanation. "If this is the case of clinical neuroscience moves, why include [function] as an end point?" He said.
Still uncertain is how to shift Lilly clinical trial will be judged by the FDA and other global regulatory agencies during the final data become available in the course of 2017. The company did submit the changes to all relevant regulators. But because a change of setting has no effect on how the study itself was conducted before data analysis, Lilly was not required to seek formal approval from the FDA or any other regulations to make the change, says Siemers.
Selkoe believes FDA sympathetic consideration solanezumab if it shows convincing evidence of cognitive benefit without functional data especially if these positive results are matched with PET encouraging data seeking to demonstrate a reduction in amyloid plaques . "We have long known that the cardinal manifestation of the disease [in the early stages] has minor problems with every day in memory, it is a very subtle process when it starts," he said. As such, Selkoe concludes, " we have to be more sophisticated "in the treatment of test," and that's what Lilly shows evidence. "
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