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Novartis Evaluating Submission Strategy for Painkiller Prexige in Various Countries Except US

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By Turna Ray

Despite a report that Novartis intends to resubmit its application for the painkiller Prexige to the US Food and Drug Administration with a companion genetic test, the Swiss drugmaker says that it is not trying to relaunch the drug in the US market.

According to an article in Bloomberg this week, Michael Nohaile, head of Novartis's molecular diagnostics unit, said 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 spokesperson said there were inaccuracies in the Bloomberg story. By the time this article went to press, Bloomberg had not yet run a correction online or retracted the story.

According to the Novartis spokesperson, the drugmaker is discussing with health regulators around the world its submission strategy for Prexige.

"Novartis is not planning to re-submit the application to the FDA," the spokesperson said. "We are working with health authorities around the world and will disclose our submissions strategies as soon as they are finalized."

Although Novartis has the capability to develop a diagnostic in-house through the molecular diagnostics unit it launched earlier this year, according to the spokesperson, the company may outsource the development of the companion diagnostic for Prexige.

"Novartis is currently evaluating commercially available tests. We cannot confirm that a Novartis diagnostic will be developed in-house," the spokesperson said.

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. Health regulators in the UK, Germany, Australia, and Canada also suspended marketing of Prexige around the same time the FDA did.

Even if Novartis says not it is not planning to resubmit its application for Prexige to the FDA, there are plenty of other markets where the drug can be reintroduced with a companion diagnostic.

As far as the US market, from the day Novartis received its "not approvable" letter from the FDA, it has made no secret of its desire to reintroduce the drug and had said the agency was amenable to such discussions.

"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."

At the time, Novartis countered FDA's rejection of its NDA with a statement suggesting that wasn't the end of the story for Prexige.

Novartis highlighted 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. Additionally, the company said clinical data showed Prexige to be safer in terms of causing less gastrointestinal complications than other NSAIDs.

"Despite this data, the FDA deemed Prexige not approvable," Novartis said at the time in a statement.

If Novartis or a third party 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.

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. However, this black mark might be slightly easier to manage in the US, since the company has submitted an alternative trade name for Prexige for US regulatory approval.

Initially, Novartis had pegged Prexige as a blockbuster for the company, with 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 a 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.

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