Eli Lilly: strike two for novel schizophrenia drug.
LY2140023 has missed the primary efficacy endpoint in its latest Phase II study.
Eli Lilly’s pipeline schizophrenia drug LY2140023 failed to separate from placebo in a large Phase II study, unlike the active comparator risperidone. Evidence is mounting against the drug’s efficacy, although Lilly’s commitment to a large development program will ensure that no hasty decisions are made regarding the drug’s future.
The Phase II study, termed HBBM, yielded the worst possible outcome for Eli Lilly. Neither of the two LY2140023 doses separated from placebo on the Positive and Negative Syndrome Scale (PANSS), while the active comparator risperidone produced a significant result.
HBBM is the largest completed study of LY2140023 to date, enrolling 880 patients over a seven-week treatment period. Its failure – coupled with LY2140023’s already uncertain efficacy profile – casts serious uncertainty over whether the drug will reach the market.
In LY2140023’s first efficacy study (HBBD), a 196-patient, proof-of-concept trial performed in Russia, the drug showed significant improvement versus placebo in PANSS score over four weeks, with efficacy as early as the first week. However, the drug was outperformed by its comparator, Eli Lilly’s antipsychotic blockbuster Zyprexa (olanzapine). A larger Phase II trial (HBBI), involving 669 patients over four weeks, failed to demonstrate efficacy for any of four LY2140023 doses or for olanzapine. At this point, Lilly argued that a higher-than-expected placebo response accounted for the negative study results and pointed to the failure of olanzapine, which has an established efficacy profile.
LY2140023 employs a novel and untried mode of action in schizophrenia, targeting metabotropic glutamate 2 and 3 receptors. It is hoped that the mechanism will result in a drug with a different clinical profile to the atypical antipsychotics, namely efficacy in negative or cognitive symptoms and an absence of metabolic and extrapyramidal side effects. However, such innovation comes at a higher risk of clinical failure. With two failed studies behind it, the evidence suggests that LY2140023 is now unlikely to reach the market.
For now, Lilly is still committed to developing LY2140023. A recently completed study measuring the drug’s adjunctive effect, alongside a planned interim analysis of an ongoing pivotal Phase III study, should provide the company with ample evidence to justify continuing or halting LY2140023’s development. Should LY2140023 prove successful in its ongoing trials, Datamonitor forecasts the drug to achieve peak-year schizophrenia sales in excess of $300m across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK). Despite its uncertain efficacy, LY2140023 would represent a new and differentiated treatment option that is sorely needed for schizophrenia patients.