Can Lilly capitalize on Alzheimer’s breakthrough?

Eli Lilly and Co. has apparently made major medical history by being the first to develop a drug that alters the course of Alzheimer’s disease. But whether Lilly can be the first to make major money from a disease-altering Alzheimer’s drug is still in doubt.

That’s because Wall Street analysts think Indianapolis-based Lilly almost certainly must conduct another Phase 3 clinical trial of its drug solanezumab, which will need to run even longer than the 18-month trials from which it just reported results. Solanezumab is commonly shortened to merely “sola.”

Such a trial could fail to affirm the results Lilly found in its first two Phase 3 clinical trials of sola (even their results were not entirely consistent). Or it could take so long that a competitor—and there are plenty of them—could beat Lilly to market with an effective treatment against Alzheimer’s.

“We fully expect that LLY will have to conduct further trials that are likely larger and longer than the existing database, but could conceivably be completed over the next several years,” Goldman Sachs Group analyst Jami Rubin wrote in a note to investors, referring to Lilly by its ticker symbol.  Her comments echo the sentiment of nearly all Wall Street analysts, most of whom think Lilly could not bring sola to market until 2017 or 2018.

“We note that there are many large pharma companies all competing to be the first to market with a disease-modifying drug for Alzheimer’s disease, thus LLY may not necessarily be first to market or the only company to compete,” Rubin added.

Other companies with Alzheimer’s disease drugs in or about to start Phase 3 trials include Illinois-based Baxter International and Switzerland-based Roche Group.

The stakes are huge for Lilly. The first effective Alzheimer’s drug to hit the market could garner $5 billion to $10 billion in annual sales, according to analysts’ estimates. Tony Butler, a pharmaceutical analyst at Barclay Capital, predicts that if sola were launched next year, it could reach a peak of $6 billion a year in sales. If it is launched in 2017, and other drugs compete with it, sola’s peak sales would likely be only $4 billion.

The first problem for Lilly is that sola failed the two primary goals in each of its Phase 3 clinical trials, which was to slow both the decline in thinking and daily functioning that occurs in both mild and moderate Alzheimer’s disease.

Sola did slow mental decline in mild patients 34 percent, which was statistically significant, and did slow declines in daily functioning 17 percent, a result that was encouraging but not statistically significant.

But even so, there is no historical precedent of the U.S. Food and Drug Administration's approving a drug that failed all the primary goals of its clinical trials, noted Butler.

A second problem is that, while the 34-percent decline sounds impressive, the mild patients in Lilly studies enjoyed just a two-point benefit in mental scores on the standard test given to Alzheimer’s patients, which is called ADAS-Cog. The name stands for Alzheimer’s Disease Assessment Scale-Cognitive.

By contrast, a drug already on the market, Pfizer's Aricept, which relieves the symptoms of Alzheimer’s for a time but does not slow the progression of the disease, reduces mild patient’s ADAS-Cog scores by nearly 3 points after just six months.

“The absolute change in ADAS-COG score after 18 months of treatment, however, was small,” Butler wrote in an Oct. 9 research note. “It remains controversial whether this magnitude of benefit would be significant on the single-patient level in the real world.”

A third problem is that sola is given to patients through 30-minute infusion sessions. But five drugmakers, including Lilly, are developing a class of oral Alzheimer’s drugs—called BACE inhibitors—which if effective, would be far more convenient.

“Docs we spoke with weren’t that impressed with the failed studies and limited (1-2 pts of ADAS-COG) improvement,” wrote UBS analyst Marc Goodman in a research note. “Even if we have a drug, is it even more effective than Aricept and this isn't even a pill?”

Lilly officials have yet to present their sola data to the U.S. Food and Drug Administration. They say they will talk with regulators before they decide whether to conduct another Phase 3 trial.

If another trial is needed, it would likely take Lilly 12 to 18 months to recruit clinicians and patients, probably two years to run and analyze the results, and at least another year before gaining FDA approval. That’s a four-year delay.

What sola has going in its favor is that there are no effective treatments for Alzheimer’s, and sola proved very safe in its Phase 3 trials. In addition, even though sola’s effect on mild patients was small, it grew consistently over time, leading Lilly officials to conclude that the drug’s impact will only grow the longer patients take it.

"We’re seeing with solanezumab a steady and increasing effect," said Dave Ricks, president of Lilly’s Bio-Medicines business unit, during a conference call with investors. He added, "We need to start reframinig our definition of what a good efficacy number is."