Eli Lilly & Co. plans to give solanezumab, its Alzheimer’s disease monoclonal antibody now completing Phase III studies, “every chance to succeed…and will take it through to conclusion” as long as it shows clear signs of efficacy, CEO John Lechleiter told analysts at the annual JP Morgan Healthcare conference.

Lechleiter touched on a variety of topics, including solanezumab, in his formal presentation on Jan. 10 and a follow-up break out session. The Alzheimer’s candidate is one of his company’s biggest near-term uncertainties— the company has released little information about the drug and considers it to be a high-risk bet.

Solanezumab binds to the mid-domain of A-beta, which forms amyloid plaques, which are protein deposits found in the brains of Alzheimer’s patients. Using biomarkers, Lilly scientists have shown in Phase II studies that solanezumab appears to pull certain kinds of A-beta out of the brain, but the company likely won’t release Phase III data until later in 2012. Lilly’s gamma secretase inhibitor, semagacestat, failed Phase III trials for Alzheimer’s in 2010, a big blow to the class and to Lilly’s Alzheimer’s program Also see "Bristol Opens A Phase III Door Into Gamma Secretase As Lilly Closes Another" - Pink Sheet, 25 July, 2011..

Phase III studies of solanezumab, each of which enrolls 1,000 patients with mild disease, aim to demonstrate improvement in cognition over 18 months, based on well-established daily living and cognition scales for Alzheimer’s, including the ADAS-COG, which worsens on average by about four points a year in people with the disease. The drug also is aimed at slowing progression of disease, so improvement in the ADAS-COG is imperative if solanezumab is to be clinically meaningful, Patients were selected for the trials based on stage of the disease, as determined by imaging biomarkers, Jan Lundberg, Lilly’s chief scientific officer, told analysts at the break out session.

Studies show that people with mild cognitive impairment and positive amyloid scans have a high risk of progressing to a more severe form of disease within 18 months, he added. Pfizer Inc. and partners Elan Corp. PLC and Johnson & Johnson are also expected to release Phase III data on a competing drug, bapineuzumab, targeting A-beta sometime in 2012. While solanezumab is similar to bapineuzumab, the latter binds to a different portion of A-beta, and therefore has a different mechanism of action. That said, the amyloid theory behind many novel drug candidates for Alzheimer’s has been controversial, with some scientists recently arguing that amyloid plaque is symptomatic of disease, not causative ([A#2011900229]).

Analysts also have pegged solanezumab’s chances of success as low, with Sanford Bernstein’s Timothy Anderson putting the probability at 10% to 20% in a Dec. 15 write-up of a conversation with senior Lilly scientists about the drug. In that report, Anderson quoted Eric Siemers, senior medical director of the Alzheimer’s Disease team at Lilly, as pointing out the difficulties his group and others still have in designing meaningful Phase II studies of potential therapies for the neurodegenerative condition. This is in part because such studies have to be impractically large and lengthy to obtain statistically meaningful results. Lilly’s solution, and increasingly that of others, has been to use biomarkers to help shorten the trial duration and improve the utility of small sample sizes.

Also, the use of biomarkers in diagnosing and monitoring Alzheimer’s disease patients is still highly experimental – at a stage which Lundberg, in the conversation with analysts, termed “the frontier of Alzheimer’s Disease biology.” In late 2010, Lilly bought the neuroradiology imaging company Avid Radiopharmaceuticals Inc. for $300 million up front plus earn outs in order to augment its biomarker program; in 2011, FDA issued a “Complete Response” Letter for the company’s positron emission tomography imaging agent, which directly images amyloid plaque, in part because it was concerned that doctors wouldn’t use the agent properly. Lilly is working on a resubmission package.

Lilly executives have told Wall Street that they will provide an update about the drug on the company’s Jan. 31 fourth-quarter earnings call, which comes shortly after the data safety board monitoring the trials makes a futility report.

Tradjenta Making Headway

Lilly’s diabetes pipeline is robust, with two novel basal insulin compounds in Phase III as of mid-2011, Lechleiter said. Lilly expects to complete its first Phase III trials for empagliflozin, an SGLT2 inhibitor, later in 2012.

Tradjenta (linagliptin), a DPP-4 inhibitor that Lilly is co-marketing as part of a diabetes partnership with Boehringer Ingelheim GMBH, is continuing to gain market share in every segment and outperforming the competition in hospitals, although it is third in its class to market, said Enrique Conterno, president of Lilly Diabetes, in response to analysts’ questions. Tradjenta, which the partners launched in the U.S. in May, is also gaining managed care formulary acceptance, with 30% of plans putting it on formulary as of Jan. 1, 2012, because the majority of the market is not “winner take all,” he noted. About 50% of plans will cover the drug as of April 2012, he predicted, and the drug is capturing 25% of new scripts written by endocrinologists. It has about a 10% share of scripts written by primary care physicians, where access has been a limitation, he said.

Lechleiter once again reiterated his position from earlier this month that the company would not consider cutting R&D or other expenses in light of its patent cliff woes. Higher-than expected SG&A and R&D spend caused it on Jan. 5 to confirm previously released 2012 guidance, but also warned analysts that their estimates were largely overly optimistic and out of line with the company’s previously-released 2012 earnings guidance.

As a result, analysts have queried the company hard about cutting costs to maintain earnings momentum—a step Lechleiter has emphatically rejected and did so again at the JP Morgan meeting. “We have 20 molecules in Phase II and the next challenge will be how to run 13 Phase III programs,” he said.

“Our labs have never been more productive than in the last five to six years…We are at the beginning of a new era for this industry and the biggest challenge is to make this business more sustainable long-term,” the exec added.

In addition, Lilly has three key assets in the pipeline directed at immunology, an area in which it is not currently active, and sees “autoimmune disease as a growth area,” he said. This includes an anti-IL 17 monoclonal antibody, which entered Phase III trials in December 2011 for moderate to severe chronic psoriasis, making a total of 12 potential new medicines in Phase III testing, Lechleiter said. Initial Phase II data for the drug was presented at a Gene To Clinic Conference in London late last year, with a more complete data set to be published in Alzheimer’s and Dementia, a peer-reviewed journal, later in 2012.

Lilly To Give High-Risk Alzheimer’s Drug “Every Chance,” says Lechleiter At JP Morgan

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