IHS Global Insight Perspective | |
Significance | Preliminary Phase III clinical trial results of Eli Lilly (U.S.)'s semagacestat showed no reduction in indicators such as disease progression, and a worsening of clinical measures. Separately, the firm's antidepressant Cymbalta (duloxetine HCI) is being reviewed by an expert panel for a potential pain indication. |
Implications | Both developments represent increasing challenges for Eli Lilly in the aftermath of generic competition against one of its top drugs—Strattera (atomoxetine). In the case of Cymbalta, the U.S. FDA's queries pertained to the safety and effectiveness of the drug as a chronic pain medication and doubts were cast over the statistical methods of the study. |
Outlook | Eli Lilly's advanced drug candidate pipeline with respect to neurodegenerative diseases will take a hit in the short term due to the exit of semagacestat. In the context of Cymbalta, the panel will delve into the safety profile and its possible effects when available to a much larger patient population. |
Alzheimer's Drug Clinical Programme
U.S. pharma major Eli Lilly has announced the halting of a drug-development programme for the experimental candidate semagacestat, a gamma-secretase inhibitor. The company was seeking to establish the drug as a potential treatment for Alzheimer's disease. The move to halt the semagacestat clinical programme was in response to disappointing preliminary results from two ongoing long-term Phase III clinical studies—Identity (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and Identity-2. Lilly states that the results showed no slowing of disease progression, a vital measure, and does show worsening of other clinical indicators, such as cognition and ability to perform daily living activities. The Phase III trials compared semagacestat with placebo involving 2,600 patients with mild-to-moderate Alzheimer's disease. Apart from worsening cognition and daily living activities ability, the trials showed semagacestat associated with increased risk of skin cancer compared to placebo. The company is to continue clinical trials of solanezumab, its other Alzheimer's drug candidate.
Cymbalta Review
Separately, the firm's intention to expand its Cymbalta drug franchise with additional indications may have hit a road block. The U.S. FDA has announced that it will seek to get expert opinion from its panel—the Anaesthetic and Life Support Drugs Advisory Committee. The panel are to review the safety and effectiveness of the drug. FDA briefing documents indicate that agency officials are concerned about the hepatotoxicity associated with the product. Eli Lilly is basing its new drug application for chronic pain referring to the drug's efficacy as a treatment for diabetic peripheral neuropathy and fibromyalgia. In its review of the clinical analysis presented by Eli Lilly on Cymbalta's efficacy, the FDA noted that several key points were "problematic". This included the MMRM (mixed models repeated measures) analysis methodology, which was found "not appropriate" for a chronic pain trial as it assumes dropouts occur at random, and utilises data from patients who withdrew early from the trial, the agency said. The full FDA document can be accessed here.
Cymbalta was initially approved in 2004 for the treatment of major depressive disorder, and subsequently approved for the indications of pain associated with diabetic peripheral neuropathy (DPN) in 2004, generalised anxiety disorder, and maintenance treatment of major depression in 2007, and fibromyalgia in 2008.
Outlook and Implications
The developments represent a disappointing phase for Eli Lilly, wherein it has faced a series of challenges on the marketed and drug discovery portfolio front. Since late July this year, the firm has encountered three significant corporate events. A U.S. Court of Appeals ruled in favour of patent challenger Sun Pharma (India) on Eli Lilly's Gemzar (gemcitabine), finding the method-of-use patent as invalid. The firm's pulmonary arterial hypertension drug Adcirca (tadalafil) received a recommendation from the Transparency Commission of France's Higher Authority on Healthcare (Haute Authorité de Santé, HAS) for use in patients with only class 2 or 3 disease, to be prescribed by specialists in pneumology, cardiology, or internal medicine. The drug was only given a medical benefit (Service Médical Rendu, SMR) of moderate in its indication. The third major blow came from a U.S. District Court ruling that Eli Lilly's Strattera (atomoxetine) method-of-use patent is invalid, opening the gates for earlier generic competition. Lilly has responded by revising its financial outlook estimates, reflecting the potential impact on revenues as a result. The larger question is the firm's commercial potency in the medium term.
With respect to Cymbalta, the agency's panel is expected to delve into the safety profile of the drug. Cymbalta currently includes in its product label a class boxed warning for suicidality in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Other serious adverse events associated with Cymbalta and noted in the label include hepatotoxicity, orthostatic hypotension and syncope, serotonin syndrome, seizures, bleeding, and effects on blood pressure. Reviewers will evaluate the potential effects of the drug, which would be (if approved) available to a much larger patient population than the current 15 million and the possible safety issues that are likely to arise.
Related Articles
- United States: 13 Aug 2010: Eli Lilly Loses Strattera Patent, Outlook Revised
- United States - France: 9 August 2010: Lilly's Adcirca Granted Poor ASMR Rating by France's Transparency Commission
- United States - India: 30 July 2010: U.S. Court Rules in Favour of Sun Pharma in Gemzar Patent Litigation