BOSTON – According to an official with Eli Lilly, the Indianapolis-based company is “really on board with personalized medicine” and considers targeting drugs to specific market segments to be “the norm.”
John Lechleiter, president and chief operating officer for Lilly, described the company’s approach to personalized medicine at a conference here last week hosted by Harvard-Partners Center for Genetics and Genomics.
Lechleiter said that while critics of personalized medicine complain that it will segment populations and decrease market shares for big pharma’s cash cow drugs, “market segmentation has really been the norm” at Lilly.
According to Lechleiter, approximately 90 percent of drugs in clinical development at Lilly have biomarkers associated with them and these biomarkers come into play earlier in drug development. This “allows us to weed out unpromising candidates, adapt trials midstream, explore secondary indications more quickly, and run efficient trials,” Lechleiter said.
Lechleiters comments echo those of other Lilly officials, including Eiry Roberts, vice president of medical projects and programs at Lilly, who recently spoke to Pharmacogenomics Reporter about the company’s overall strategy for personalized medicine using pharmacogenomics techniques.
Roberts said that strategy involves using PGx along with “more established” tools to improve patient outcomes and, in turn, increase the likelihood that patients will adhere to treatments [see PGx Reporter 11-28-2007].
Clinical researchers estimate that for most prescribed drugs, compliance hovers between 50 percent and 60 percent. Industry observers have noted that by improving patient compliance, drug companies can increase sales of their products, as well.
Lechleiter offered some additional examples of how genomics-based personalized medicine is coming into play at the company.
For instance, Lilly acquired in 2004 a company called Applied Molecular Evolution to help it customize antibodies in early drug development. Following this, Lilly and Applied Molecular Evolution designed a molecule to treat patients that don’t respond to the non-Hodgkin’s lymphoma drug Rituxan, Lechleiter said.
For another study involving an investigational acute coronary syndrome drug, when Lilly completed clinical trials, the drug showed a favorable benefit/risk profile in a majority of patients but in three subgroups the drug at the given dosage raised risks for adverse reactions. Although this drug is investigational, genomic-based personalization strategies allowed Lilly to more finely tune benefit/risk calculations for the product, Lechleiter said.
Lilly has also been working over the last two years with ParAllele, using a transporter chip based on Affymetrix’s GeneChip technology to broadly genotype patients in its clinical trials and help it understand a broad spectrum of drug-metabolizing enzymes. ParAllele will take the lead, with Lilly’s support, in taking any resulting diagnostic through the FDA regulatory process. Lilly would not say when it intends to submit its application for such a diagnostic to the agency.
Using targeted markers to personalized medicine “isn’t such a scary prospect” from an economic standpoint.
Additionally, Lilly is using PGx to avoid serious adverse reactions in certain patients using the sepsis drug Xigris. Lilly entered into a collaboration last year with BioSite to provide bedside testing of serum markers of activated protein C, which Lilly hopes will help identify patients that should receive Xigris.
Xigris is a recombinant version of human activated protein C that manages microvascular function by decreasing inflammation and coagulation and increasing fibrinolysis. In 2005, Lilly updated the label for the drug to warn of an increased risk of mortality with the drug in patients with single organ dysfunction and following recent surgery.
Lastly, Lilly is using PGx to develop diagnostics for cancer treatments. Lilly and the Phoenix, Ariz.-based non-profit Translational Genomics Research Institute announced in July that researchers had identified an altered form of AKT1 that appears to play a role in tumor cell proliferation and cell resistance to certain therapies.
The finding may lead to the development of a diagnostic in breast, colorectal, and ovarian cancer if additional research shows that a therapy targeting this polymorphism will confer a survival advantage in patients [see PGx Reporter 07-11-2007].
According to Lechleiter, using markers to identify target patients may create smaller markets for drugs, but the practice could also have a positive economic impact within those market segments, since targeting the right drug to the right patient improves response rates, drives faster uptake, and protects non-responders from drug-related adverse events.
A company’s market gain for a drug in a biomarker-defined population depends on the frequency of use and response rate within that market, Lechleiter said. As an example, he described a hypothetical marker with a 25 percent frequency for which peak sales in three different scenarios, based on the rate of responders and non-responders, yielded sales of 33 percent, 66 percent, and 122 percent above what the sales of the product would be in an unsegmented population.
Given this example, Lechleiter noted that using targeted markers to personalize medicine “isn’t such a scary prospect” from an economic standpoint.
While a Lilly official previously told Pharmacogenomics Reporter that biomarker-based PGx studies cost more and are more complex than traditional clinical trials [see PGx Reporter 04-18-2007], Lechleiter said that he and others at Lilly believe that biomarker-driven strategies will lower the overall cost of drug development and decrease cycle times.