This article has been updated from a previous version based on comments from a Novartis spokesperson.
By Turna Ray
Novartis is evaluating its submission strategy for a pain killer — previously denied marketing approval by the US Food and Drug Administration — with health regulatory authorities around the world and is planning to develop a companion genetic test that can determine which patients will develop side effects when treated with drug.
Michael Nohaile, head of Novartis's molecular diagnostics unit, told Bloomberg this week that the Swiss drug giant might re-submit a marketing application for Prexige to the FDA later this year along with a genetic test that can determine those at risk for experiencing liver damage upon taking the drug. The story suggested that this diagnostic would be developed by Novartis' new in-house molecular diagnostics unit.
However, in a statement to Pharmacogenomics Reporter, a Novartis official said there were inaccuracies in the Bloomberg story. Bloomberg has not yet run a correction.
"Novartis is currently evaluating commercially available tests. We cannot confirm that a Novartis diagnostic will be developed in-house," the spokesperson said. "Also, Novartis is not planning to re-submit the application to the FDA. We are working with health authorities around the world and will disclose our submissions strategies as soon as they are finalized."
Novartis launched the internal molecular diagnostics unit in January, hoping to spur Rx/Dx co-development products by matching genetic tests with therapeutics in the early stages of clinical trials. This strategy, simultaneous development of a drug and a companion diagnostic, is widely considered to be advantageous for companies when dealing with regulatory authorities and conducting clinical trials in a prospective fashion.
Unfortunately, Prexige's road to personalization isn't the ideal example of an Rx/Dx match-up.
The FDA in 2007 refused to approve Prexige, commonly known as lumiracoxib, as a treatment for patients suffering from osteoarthritic pain based on clinical trial data that showed the COX-2 inhibitor caused serious liver side effects in some patients.
According to Novartis, Prexige is currently approved in more than 50 countries. The Australian and Canadian regulatory authorities pulled Prexige off the market around the same time the FDA did. The company has said previously that it has submitted an alternative trade name for this medicine to the FDA.
Even if Novartis says it is not planning to resubmit its application for Prexige to the FDA, there are plenty of other markets where the drug is still marketed and can be reintroduced with a companion diagnostic.
At the time FDA issued its "not approvable" letter for Prexige, Novartis countered with a statement suggesting that FDA's rejection of its marketing application wasn't the end of the story for Prexige.
"The FDA noted in its response that it remained open to exploring the use of this medicine in patients where Prexige would provide an acceptable benefit-to-risk balance," Novartis said at the time. "This group could include patients with a higher incidence of gastrointestinal complications, including those suffering from ulcers or being treated with anticoagulants."
If Novartis successfully develops a companion diagnostic for Prexige that can gauge which patients are at increased risk for hepatic side effects, then it would be the first example of pharmacogenomics resuscitating a failed drug.
Supporters of personalized medicine have often said that pharmacogenomics may be a useful tool for pharmaceutical companies on several fronts — running more efficient and cheaper clinical trials, increasing the efficacy of targeted drugs, and reviving drugs that have failed trials due to serious side effects.
Now there are a number of marketed Rx/Dx combination products, where a companion diagnostic can determine which patients will respond to a drug — as in the case of oncologics Herceptin, Erbitux, and Vectibix — and there are marketed tests that pinpoint which patients will develop serious side effects associated with a drug — such as the HIV drug abacavir and the anticoagulant warfarin. However, there are no examples in the US where a drug rejected by the FDA for serious side effects has made a comeback with the help of a genetic test.
Even though it may be scientifically possible to discern genetic subpopulations that would not suffer the side effects of a drug, once a drug has been rejected or pulled off the market by the regulatory authorities for safety issues, some industry insiders have questioned whether resuscitating that drug will ever be possible from a marketing standpoint.
The difficulties associated with shedding the "failed drug" stigma, may be why Novartis is backing away from statements that it will try to reintroduce Prexige in the US market.
Of course, the campaign to reintroduce Prexige to the public and to investors began as soon as Novartis received the "not approvable" stamp from the FDA two years ago.
At the time, the Swiss drug giant responded to FDA's rejection by maintaining that the hepatic side effects seen with Prexige were no different than those seen with other currently available pain killers in the non-steroidal anti-inflammatory class.
Furthermore, Novartis touted that Prexige reduced the incidence of serious upper gastrointestinal complications by 79 percent when compared to two other NSAIDs, naproxen and ibuprofen. The company also noted that in its study involving more than 18,000 patients, Prexige users had no cases of jaundice or hepatic failure on the 100 mg once-daily dose.
"Despite this data, the FDA deemed Prexige not approvable," Novartis said at the time in a statement.
Initially, Novartis had hoped Prexige would be a blockbuster for the company, with projected annual sales of more than $1 billion. What slice of that market Novartis hopes to capture now will depend on how prevalent the genetic targets are that would predispose people to experiencing liver side effects with Prexige.
If Novartis successfully reintroduces Prexige with a companion diagnostic in specific subpopulation of patients, then it would be first PGx-based painkiller on the market. Still, the market for painkillers is crowded, and Novartis will have the challenge of differentiating Prexige from numerous other options, even in a genetically targeted subpopulation.