HEALTH INDUSTRY APRIL 26, 2011
Lilly Tests New Schizophrenia Drug
By PETER LOFTUS wsj.com
Eli Lilly & Co. hopes to introduce the first of a new class of schizophrenia drugs that sidesteps the weight gain linked to current treatments—and which might work best in people with a certain genetic makeup.
After seeing signs of promise in earlier tests, Indianapolis-based Lilly recently started large-scale, late-stage clinical trials of the drug, code-named LY2140023, some of which are expected to be completed by early 2013.
If the trials are successful and regulators approve it, the drug could hit the market in 2014 and eventually generate $1 billion in peak annual sales, estimated BMO Capital Markets analyst Robert Hazlett. "It's a novel approach that appears to be effective, at least modestly," Mr. Hazlett said.
Lilly is betting on the schizophrenia drug and other potential new products to help replace revenue due to be lost in coming years to patent expirations that trigger generic competition for top-selling drugs, including its antipsychotic Zyprexa.
There is no guarantee the Lilly drug's safety, efficacy or genetic link will be born out by the larger clinical trials. While weight gain may not be an issue, there have been other safety and efficacy issues in trials to date. Even if the drug makes it to market, it will face competition from cheaper generics and possibly newer schizophrenia drugs under development at such companies as Roche Holding AG.
Lilly says there is an unmet medical need in schizophrenia, a mental illness in which patients experience hallucinations, delusions and other symptoms. Widely used drugs known as atypical antipsychotics–which include Zyprexa and AstraZeneca PLC's Seroquel–carry safety risks including weight gain and elevated blood sugar (the companies have paid hundreds of millions of dollars to settle lawsuits alleging the drugs caused diabetes and other injuries).
LY2140023 is designed to stimulate substances in the brain known as metabotropic glutamate receptors, or mGlu for short. This approach differs from atypicals, which generally block the effects of the chemical dopamine in the brain.
One midstage study published in Nature Medicine in 2007 showed Lilly's drug improved symptoms versus a placebo and didn't increase the risk of weight gain. "It's actually a side-effect profile that's much more attractive from a long-term view," said Jan Lundberg, head of Lilly's research and development arm.
In another study released in 2009, however, the drug performed no better than placebo. But Lilly deemed the outcome inconclusive because the study's design may have contributed to higher-than-normal improvements in placebo recipients.
In a six-month safety study presented at a medical conference this month, the drug was comparable to standard treatments including Zyprexa in the time to treatment discontinuation due to lack of tolerability. However, discontinuation due to lack of efficacy was significantly greater for LY2140023 compared with standard treatment. Mr. Hazlett, the BMO analyst, said the drug's efficacy is acceptable but not its strong suit.
Lilly's LY2140023 was associated with higher rates of insomnia, vomiting, agitation and indigestion, while patients on standard treatment had higher rates of weight gain and a movement disorder.
One patient in the trial had two seizures a day after discontinuing three weeks of treatment of the Lilly drug and initiating treatment with a conventional antipsychotic. The patient recovered with no residual side effects, researchers reported.
Joseph T. Coyle, a professor of psychiatry and neuroscience at Harvard Medical School who has studied the role of glutamate receptors in schizophrenia, said the Lilly drug has potential to improve treatment of so-called negative symptoms of the disease, which include social withdrawal, and cognitive symptoms, while avoiding weight gain. But he said that needs to be proved in late-stage trials. He has consulted for Lilly previously but isn't directly involved in developing Lilly's mGlu drug.
The potential genetic angle is part of a broader shift toward "personalized medicine," or the use of genetic information to determine whether individual patients are likely to respond to certain drugs.
A study published last year in the Pharmacogenomics Journal found patients with certain DNA sequences treated with the Lilly drug showed the largest reduction in schizophrenia symptoms.
"Intriguing preliminary data suggest it could be possible to identify a subpopulation of patients which responds better," Mr. Lundberg said. Lilly will track how LY2140023 performs in a predefined genetic subpopulation of patients in its late-stage trials, he said.
Dr. Coyle called the potential genetic link "preliminary," and said more comprehensive genetic analysis would be needed before concluding that it will be possible to identify in advance which patients are likely to benefit from the Lilly drug.
Lilly Tests New Schizophrenia Drug
By PETER LOFTUS wsj.com
Eli Lilly & Co. hopes to introduce the first of a new class of schizophrenia drugs that sidesteps the weight gain linked to current treatments—and which might work best in people with a certain genetic makeup.
After seeing signs of promise in earlier tests, Indianapolis-based Lilly recently started large-scale, late-stage clinical trials of the drug, code-named LY2140023, some of which are expected to be completed by early 2013.
If the trials are successful and regulators approve it, the drug could hit the market in 2014 and eventually generate $1 billion in peak annual sales, estimated BMO Capital Markets analyst Robert Hazlett. "It's a novel approach that appears to be effective, at least modestly," Mr. Hazlett said.
Lilly is betting on the schizophrenia drug and other potential new products to help replace revenue due to be lost in coming years to patent expirations that trigger generic competition for top-selling drugs, including its antipsychotic Zyprexa.
There is no guarantee the Lilly drug's safety, efficacy or genetic link will be born out by the larger clinical trials. While weight gain may not be an issue, there have been other safety and efficacy issues in trials to date. Even if the drug makes it to market, it will face competition from cheaper generics and possibly newer schizophrenia drugs under development at such companies as Roche Holding AG.
Lilly says there is an unmet medical need in schizophrenia, a mental illness in which patients experience hallucinations, delusions and other symptoms. Widely used drugs known as atypical antipsychotics–which include Zyprexa and AstraZeneca PLC's Seroquel–carry safety risks including weight gain and elevated blood sugar (the companies have paid hundreds of millions of dollars to settle lawsuits alleging the drugs caused diabetes and other injuries).
LY2140023 is designed to stimulate substances in the brain known as metabotropic glutamate receptors, or mGlu for short. This approach differs from atypicals, which generally block the effects of the chemical dopamine in the brain.
One midstage study published in Nature Medicine in 2007 showed Lilly's drug improved symptoms versus a placebo and didn't increase the risk of weight gain. "It's actually a side-effect profile that's much more attractive from a long-term view," said Jan Lundberg, head of Lilly's research and development arm.
In another study released in 2009, however, the drug performed no better than placebo. But Lilly deemed the outcome inconclusive because the study's design may have contributed to higher-than-normal improvements in placebo recipients.
In a six-month safety study presented at a medical conference this month, the drug was comparable to standard treatments including Zyprexa in the time to treatment discontinuation due to lack of tolerability. However, discontinuation due to lack of efficacy was significantly greater for LY2140023 compared with standard treatment. Mr. Hazlett, the BMO analyst, said the drug's efficacy is acceptable but not its strong suit.
Lilly's LY2140023 was associated with higher rates of insomnia, vomiting, agitation and indigestion, while patients on standard treatment had higher rates of weight gain and a movement disorder.
One patient in the trial had two seizures a day after discontinuing three weeks of treatment of the Lilly drug and initiating treatment with a conventional antipsychotic. The patient recovered with no residual side effects, researchers reported.
Joseph T. Coyle, a professor of psychiatry and neuroscience at Harvard Medical School who has studied the role of glutamate receptors in schizophrenia, said the Lilly drug has potential to improve treatment of so-called negative symptoms of the disease, which include social withdrawal, and cognitive symptoms, while avoiding weight gain. But he said that needs to be proved in late-stage trials. He has consulted for Lilly previously but isn't directly involved in developing Lilly's mGlu drug.
The potential genetic angle is part of a broader shift toward "personalized medicine," or the use of genetic information to determine whether individual patients are likely to respond to certain drugs.
A study published last year in the Pharmacogenomics Journal found patients with certain DNA sequences treated with the Lilly drug showed the largest reduction in schizophrenia symptoms.
"Intriguing preliminary data suggest it could be possible to identify a subpopulation of patients which responds better," Mr. Lundberg said. Lilly will track how LY2140023 performs in a predefined genetic subpopulation of patients in its late-stage trials, he said.
Dr. Coyle called the potential genetic link "preliminary," and said more comprehensive genetic analysis would be needed before concluding that it will be possible to identify in advance which patients are likely to benefit from the Lilly drug.