Novartis is “actively exploring” drug-diagnostic co-development deals in the early development phases, and expects to integrate the concept for later phases of development within the next three to five years, according to a company official.
In addition, the Swiss drug company has recently penned an agreement with Canada-based Warnex to use its pharmacogenomics tools to identify suboptimal doses for its cancer drug Gleevec.
The company has made no secret of the fact that it is abandoning traditional R&D models for the so-called learn-and-confirm strategy, involving a heavy dose of pharmacogenomics and biomarkers, to learn about drug candidates earlier in the development process.
In addition, Novartis officials publicly decreed that the blockbuster will die in the next 10 years and expressed that “niche-busters” – targeted drugs with applicability across several disease markets – may be the pharmaceutical industry’s profit model for the future [see PGx Reporter 03-28-07]
Last week, Trevor Mundel, head of exploratory clinical development at Novartis, provided Pharmacogenomics Reporter even more clarity on how PGx and drug-diagnostic co-development fit into the company’s restructured R&D and business strategy, and in what he calls the “chang[ing] landscape for the pharma industry.”
With a number of high-profile drug candidate failures, soaring drug development costs, and the impending loss of marketing exclusivity for a number of blockbuster drugs, it is a nervous time for the pharmaceutical industry.
According to Mundel, Novartis is“committed” to developing predictive technologies, particularly pharmacogenomics, which the company views as a clinically and economically useful tool in drug development.
While some naysayers feared that PGx would eat into the industry’s profit model, others have long held that big pharma will reinvent the blockbuster using biomarkers and pharmacogenomics opportunistically to arrive more efficiently at cash-cow drugs.
“We have thousands of state-of-the-art samples supporting PGx R&D activities that can integrate new formats and/or new technologies,” Mundel wrote in an e-mail to Pharmacogenomics Reporter this week.
Pharmacogenomicsis “an important element in the drug discovery process that generates substantial benefits for patients by avoiding unnecessary treatment, increasing diagnostic precision, and anticipating adverse events. At the same time, PGx optimizes our cost and resource allocations by more stringently selecting drug trial candidates,” he wrote.
“We expect these early investments [in PGx] to return considerable savings in development costs when optimized, biomarker-based clinical trials provide earlier and more focused efficacy data.”
One way Novartis is currently using PGx is to more accurately define, diagnose, and treat cancer patients, according to Mundel. Last week, Novartis Canada hired Warnex to perform bioanalytical and pharmacogenomic services for the drug maker’s leukemia and intestinal tumors program.
Warnex said in a statement that its Bioanalytical Services division will use liquid chromatography and mass spec technologies to test blood levels of Novartis’ chronic myeloid leukemia drug Gleevec to “help identify non-adherence or suboptimal dosing.” Warnex also will perform PCR-based diagnostic tests to determine if patients have chromosomal abnormalities.
“Gleevec is an excellent example in which treatment is indicated in patients with Philadelphia chromosome-positive chronic myeloid leukemia and bcr-abl expression levels are used for response monitoring,” Mundel wrote.
He added that Novartis also has projects looking at patients' mutational status in therapeutic targets to help the company better enroll or stratify clinical trials.
Mundel said that Novartis’ acquisition of Chiron last year will help the company fulfill its drug-diagnostic co-development strategy. After buying Chiron for $5.1 billion, Novartis created a new division, called Novartis Vaccines & Diagnostics, combining its own vaccines business with Chiron’s blood-testing and diagnostics group.
Novartis is “actively exploring [drug-diagnostic co-development deals] in the early development phases, and expects to integrate the concept for later phases of development within the next three to five years.”
“The current blood testing business, combined with some of Novartis’ in-house diagnostic expertise, provides the platform to grow and expand this business unit and to investigate opportunities in molecular diagnostics,” Novartis said in a filing with the US Securities and Exchange Commission at the time.
According to Mundel, the US Food and Drug Administration also has a role to play in encouraging drug makers to adopt PGx technologies by providing a regulatory framework encouraging Rx-Dx co-development, drafting regulation to reduce the risk for drug and diagnostic companies, and protecting personal data.
“In general, the FDA should further encourage and support the use of PGx endpoints in pharmaceutical development, for example by increasing the number of CRADAs concerning PGx,” Mundel added.
FDA and Novartis currently have a CRADA, under the Critical Path’s Predictive Safety Testing Consortium, to identify nephrotoxic biomarkers that predict the effects of certain drugs on kidney function. Data from this collaboration will be used to build a preclinical genomic biomarker-qualification process.
But according to Mundel, the science has to mature before the FDA can more readily integrate PGx-based considerations into its regulatory process.
“At this point FDA is still learning and continues to make these decisions on a case-by-case basis,” he said.
One way the FDA is learning about pharmacogenomics is through its Voluntary Genomics Data Submission program. The agency launched the program in 2004 as a way to learn how drug makers use various pharmacogenetic technologies, but pledged not to use the data in its review process.
However, an FDA official recently said that drug companies have been “strategically” using the program to help populate Phase III trials with genetically favorable volunteers [see PGx Reporter 01-03-07]. According to Mundel, Novartis has used the VGDS program to share results of exploratory pharmacogenetic analyses from two clinical trials.
“We found the program to be a useful means to discuss genetic data analysis and genotyping technologies with the agency in a highly interactive manner,” Mundel wrote in his e-mail. “We are currently reviewing other potential submissions for this year.”