Eli Lilly is hoping its decision to partner with pharmacogenetics consultancy Cabernet Pharmaceuticals will improve its luck with the US Food and Drug Administration submissions, and perhaps even lead to new blockbuster drugs.
“We are optimistic that additional information on who should or should not take our new products will be viewed favorably by regulatory authorities,” Stephen Eck, Lilly’s vice-president translational medicine and PGx, told Pharmacogenomics Reporter last week.
He spoke after Lilly announced the Cabernet partnership, making the company the first drug maker to hire the consultancy.
“Understanding the genetic contribution to variations in response to new medicines, primarily safety and efficacy, is highly cost effective,” said Eck. “Knowing which patients derive the most benefit from a new medicine will improve uptake by physicians and patients. In the long run this creates value for all parties.
“In some cases we may identify products that are especially well suited for a portion of the larger patient population,” said he added. “In these instances, using genetic testing to identify these patients may prove essential for a drug's success in the marketplace.”
For the time being, both Cabernet and Lilly are keeping a tight lid on what drug programs or disease areas they will tackle. According to Eck, the partners will focus on a variety of therapeutic areas important for Lilly.
“The scope of the work will range across development projects designated by Lilly,” Cabernet CEO Allen Roses told Pharmacogenomics Reporter last week. “The focus here is PGx as it can really fit in with the day-to-day work of drug development and help to inform pipeline decisions.”
Cabernet, based in Durham, NC, specializes in applying PGx strategies to the drug-development and post-marketing setting; designing PGx studies; communicating PGx data to regulatory authorities; genotyping samples; facilitating DNA collection; and obtaining informed consent during clinical trials.
“Which types of service Lilly will use will be up to Lilly,” noted Roses, who had been head of genetics research at GlaxoSmithKline. “What Cabernet is offering is a flexible resource so that clients can take what they need while managing the dynamic progression of their pipelines.”
As part of their alliance, Cabernet will help Lilly cherry-pick the drug candidates in early clinical development that are most likely to clear clinical trials and FDA regulatory review.
“The focus [of the alliance] is [to use] PGx as it can really fit in with the day-to-day work of drug development and help to inform pipeline decisions.”
“We want to know earlier which patient groups are most likely to get benefit and which are most likely to experience side effects, and thus know whom to enroll into clinical trials as they progress,” Roses said. “In other words, we get the information in the early trials as the drug moves toward a proof-of-concept decision, and then we use the information in designing subsequent trials.
“Obviously, once the drug gets to market, PGx can then guide prescribing decisions as well, to the benefit of patients,” added Roses.
According to widely cited industry statistics, approximately 60 percent of investigational drugs fail Phase II clinical trials while 56 percent fail in Phase III.
Based on the “interest expressed by the people we're talking to … everyone wants to reduce the high attrition rates in R&D pipelines,” said Roses, who is also director of Duke University’s Deane Drug Discovery Institute.
When he launched Cabernet earlier this year, Roses said he intended to staff Cabernet with the “brain power … at the universities and the know-how across the pipeline … in big pharma.” [see PGx Reporter 01-30-2008].
According to Roses, Cabernet is currently staffed by PGx experts from industry. However, he noted that the company is looking to hire additional experts from industry and academia who have experience applying pharmacogenetics to an R&D pipeline. Lilly is Cabernet’s first customer.
“Cabernet provides highly trained individuals that complement our existing workforce,” Eck noted. “The current arrangement allows us to rapidly expand our capability and capacity while creating a more flexible cost base.”
Financial terms of the deal were not disclosed.
’We are Going to Die’
Lilly has long said that it is committed to employing pharmacogenetic strategies to help it improve the safety and efficacy of its drugs [see PGx Reporter 12-05-2007]. According to company officials, as much as 90 percent of drugs in clinical development at Lilly have biomarkers associated with them, and the firm is betting they will come into play earlier in the drug-development pipeline to help its researchers make smarter go/no-go decisions and run more efficient trials.
The drug maker relied on PGx tools and strategies before it hired Cabernet. For instance, the company has been working over the last three years with ParAllele to use a transporter chip to broadly genotype patients in its clinical trials in order to better 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.
Additionally, Lilly is using PGx tools to help identify patients who are likely to develop serious adverse reactions when using its sepsis drug Xigris. To that end, Lilly last year partnered with BioSite to test, at the patient’s bedside, for serum markers linked to activated protein C, which is associated with Xigris-induced adverse events.
The drug firm is also using PGx to develop diagnostics for cancer treatments. Lilly and the Phoenix-based non-profit Translational Genomics Research Institute announced in July 2007 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 a diagnostic for drugs against breast, colorectal, and ovarian cancer if additional research shows that a therapy targeting this polymorphism can improve mortality [see PGx Reporter 07-11-2007].
Richard Hockett, Lilly’s director of genomics, said Lilly understands that “if we don’t get on the PGx bandwagon, we are going to die.”
He said that by now some pharma companies are more invested in pharmacogenomics than others. Hockett made his remarks during a pharmacogenomics conference in Montreal last week at which Lon Cardon, Roses’ replacement as GlaxoSmithKline’s head of genetics, placed his company in the latter category when he noted that the drug giant would not build an internal biobanking initiative.
“We want to be a part of that but we will not be building our own biobanking initiative,” Cardon said. “We feel being an active participant is a better role than being a driver.”
Hockett later said that if pharma companies intend to simultaneously launch drug/diagnostic combination products, it is critical that they invest in building internal biobanks. He added that some big pharmas, including Lilly and Pfizer, do collect genetic samples as part of every clinical trial.
It is worth noting that GSK’s move away from internal R&D to a strategy of in-licensing late-stage products perhaps directly led to the birth of Cabernet. When Roses returned to academia last year after a decade of guiding genetics research at GSK, he told Pharmacogenomics Reporter that the R&D focus at the firm had ceased to hold his interest.
“The decision wasn’t so much to leave GSK,” Roses said at the time. “The decision was to go to something that was much more exciting.” Nine months later, Roses’ PGx startup inked its first consulting deal with Lilly.
Roses said that Cabernet is currently in discussions with several other potential clients in various countries.