Johnson & Johnson's Intelence (etravirine) is the first non-nucleoside reverse transcriptase inhibitor approved for the treatment of HIV infection in antiretroviral treatment-experienced adults with documented resistance to NNRTIs and other antiretroviral agents. J&J's Tibotec subsidiary announced FDA approval of Intelence Jan. 18.

"This is another significant new product for many HIV-infected patients who are NNRTI-resistant and whose infections are not responding to currently available medications," FDA Division of Antiviral Products Director Debra Birnkrant said.

"When used with other active anti-HIV medicines and when taken as prescribed, etravirine reduces the amount of HIV in the blood and increases white blood cells that help fight off other infections," FDA said. "In addition, etravirine may reduce the risk of death or infections that can occur with a weakened immune system."

Intelence is the first new NNRTI introduced in nearly 10 years. FDA approved the drug following a six-month priority review (¹ Also see "Tibotec’s Etravirine NNRTI For HIV NDA Has Jan. 18 Action Date" - Pink Sheet, 20 September, 2007.).

While NNRTIs such as Bristol-Myers Squibb's market-leading Sustiva (efavirenz) have been used in the treatment of HIV for years, their use has been limited by cross-resistance within the class.

J&J said it will make Intelence available to wholesalers within one week. The wholesale acquisition cost of the drug is $5.45 per tablet. The approved dose is for four tablets a day, two 100 mg tablets twice daily.

The NDA was based on two Phase III randomized, double-blind, placebo-controlled studies, DUET-1 and DUET-2, which examined the use of Intelence in combination with other antiretroviral medications versus placebo and background regimen in treatment-experienced adult HIV-1 patients with documented resistance to NNRTIs and protease inhibitors.

The 24-week pooled analysis of the DUET studies showed that significantly more patients in the Intelence arm achieved undetectable viral load of less than 50 copies/mL versus placebo (59.8 percent versus 40.2 percent). A significantly greater number of Intelence patients also showed a mean increase in CD4 positive cell count from baseline (mean increase of 81 versus 64 cells/mm) versus placebo.

Use of the drug should be based on resistance testing and treatment history, according to labeling. In addition, the package insert notes that the use of other antiretroviral agents with Intelence is associated with an increased likelihood of treatment response, but patients who already have experienced virologic failure on an NNRTI-containing regimen should not use Intelence in combination with only NNRTIs.

The most common adverse events reported with Intelence were rash and nausea, including rare cases of serious skin reactions such as Stevens-Johnson syndrome and erythema multiforme, according to labeling.

"The long-term effects of etravirine are not known, and its safety and effectiveness in children ages 16 years and younger has not been studied," FDA said.

Co-administration with certain antiretrovirals is not recommended, including tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, full dose ritonavir, protease inhibitors administered without ritonavir and other NNRTIs.

The approval of Intelence comes less than two years after J&J launched the first protease inhibitor, Prezista (darunavir) for treatment-resistant HIV patients (² Also see "J&J’s Prezista Approved For Treatment-Resistant HIV" - Pink Sheet, 23 June, 2006.).

"With one of the most robust virology research and development programs in the industry, we are dedicated to continuing to deliver innovative approaches in HIV management in the years to come," J&J said.

The company has sought to establish itself has a leader in virology. Last year, it announced plans to file marketing applications for four virology drugs in four years. In addition to Intelence, those drugs include the protease inhibitor telaprevir for hepatitis C in the European Union, a second NNRTI, TMC 278, and an investigational drug for multi-drug resistant tuberculosis, TMC 207.

J&J also is seeking approval of Intelence from regulatory authorities in Australia, Canada, Europe, Russia and Switzerland.

The firm announced $24.9 billion in 2007 earnings for its pharmaceuticals business today (³ Also see "J&J Pipeline On Track; Tapentadol Filing Expected This Week" - Pink Sheet, 22 January, 2008.).

- Jessica Merrill (j.merrill@elsevier.com)

J&amp;J’s Intelence Approved For HIV Treatment In NNRTI-Resistant Patients

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J&J’s Intelence Approved For HIV Treatment In NNRTI-Resistant Patients