Eli Lilly and Co. said patients with Alzheimer’s disease whose conditions worsened upon taking the experimental drug semagacestat didn’t improve after dosing was halted.
Lilly stopped development of the pill in August after data showed it harmed patients instead of helping them. The Indianapolis-based company gathered information on the failed compound for 32 weeks after patients stopped taking the treatment. Lilly presented the data Tuesday at the Alzheimer’s Association International Conference in Paris.
“We wanted to understand what happened,” Eric Siemers, senior medical director for Alzheimer at Lilly, said in an interview at the conference. “Even though semagacestat didn’t work, we feel we moved the field forward in terms of our understanding of how you develop these compounds.”
Semagacestat, which was in the last of three stages of testing usually needed for U.S. regulatory approval, was designed to block an enzyme called gamma secretase that’s tied to production of beta amyloid plaque, considered by researchers to be a main contributor to Alzheimer’s. More insight on semagacestat may clarify whether other gamma secretase inhibitors, such as Bristol-Myers Squibb Co.’s avagacestat, pose the same problem, said Marc Goodman, an analyst at UBS AG in New York.
Even seven months after patients stopped the use of semagacestat, they still had more trouble with thinking, remembering and mental functioning than those who didn’t receive the medication, Lilly said Tuesday. Patients who had taken the drug didn’t worsen further, the company said.
“The cognitive worsening wasn’t reversible,” Siemers said. “On the other hand, the lines didn’t continue to diverge. It wasn’t that we initiated some cascade that didn’t stop after you stopped the compound.” The exact reasons for which semagacestat failed are unclear and may never be known, Siemers said. The dosing was right, he also said.
About 36 million people worldwide suffer from the memory-robbing condition, according to the Alzheimer’s Association. By 2050, that number is expected to double.
The disease, first described in 1906 by the German doctor Alois Alzheimer, destroys brain cells and makes it difficult for patients to think, remember and function. Current therapies, including Forest Laboratories Inc.’s Namenda and Pfizer and Eisai Co.’s Aricept, address only Alzheimer’s symptoms and don’t cure or slow it.
“If the semagacestat data points to a significant class effect, we would see risk to Bristol’s compound,” currently in mid-stage testing, Goodman wrote in a July 14 note to clients.
William Thies, chief medical and scientific officer at the Alzheimer’s Association, doesn’t think the Bristol-Myers compound will necessarily be affected by the findings.
“We’ll see whether their gamma secretase is more selective,” Thies said in an interview before Lilly presented the data. “Typically, when new drug classes are opened up, the first agents tend to be dirty and we recognize side effects that we can attack by changing the molecule slightly.”
Siemers said he couldn’t comment on the other gamma secretase inhibitors in development as he didn’t know them well enough.
Lilly is running two final-stage trials of another Alzheimer’s treatment, solanezumab, which works against beta amyloid by trying to clear it through the bloodstream. The U.S. drugmaker needs new products to replace its schizophrenia treatment Zyprexa and other of its top-selling medicines facing generic competition.
A string of study failures over the past years, including the semagacestat one, has called into question the leading Alzheimer’s discovery strategy being pursued by companies such as Lilly, Pfizer and Johnson & Johnson: the theory that amyloid, sticky wads of protein accumulating in the brain, are the driving force of the debilitating disease.
“My problem philosophically is that nobody knows how Alzheimer’s starts and progresses, therefore the chances of hitting on a drug are very slim,” Les Funtleyder, a portfolio manager and healthcare strategist at Miller Tabak & Co. in New York, said in e-mailed comments. He has no estimate for Lilly’s solanezumab as he doesn’t think the treatment will be approved.