Intelence

Product
Intelence

Approval Date
January 18, 2008

Release Date
January 25, 2008

Companies
Tibotec Therapeutics, a division of Ortho Biotech Products

Class
Novel nucleoside reverse transcriptase inhibitor (NNRTI)

Indication
In combination with other antiretroviral agents, for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a NNRTI and other ARV agents.

Active Ingredient
Etravirine; 100mg; tabs.

Agency Roster
The CementWorks (professional)
Edelman (PR)

Marketing Strategy/Execution
Intelence is the first agent in its class to show antiviral activity in patients who have developed resistance to an NNRTI. As such reps will pitch the drug to docs as a new option in late-stage therapy for those who have failed on the other two NNRTIs, Bristol Myers Squibb’s Sustiva and Boehringer Ingelheim’s Viramune. One reason patients fail on the drugs is that they develop genetic resistance. Intelence has a higher barrier to resistance, meaning it combats the virus through a higher number of mutations. While tolerability is just as good, Intelence’s twice-daily dosing is a drawback compared to the other agents, both of which are once-a-day. But patients may be more willing to put up with twice-daily dosing in a second-line therapy, especially those struggling to find a regimen that works. The company would not confirm whether any DTC is planned, but Ortho Biotech’s parent company, Johnson & Johnson, abides by the PhRMA DTC guidelines. That means consumers won’t see any DTC for at least six months after approval.

The Market

 
Physician Outlook
Johnson & Johnson/Tibotec Therapeutics recently received FDA approval for Intelence (Etravrine/TMC125), the first next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) and the first NNRTI launched in the past 10 years. Its specific indication is for treatment-experienced patients with treatment failure on other highly active antiretroviral (HAART) regimens. Top HIV thought leaders are enthusiastic about Intelence for several reasons, first and foremost the fact that it has anti-viral activity in patients who already have certain resistance mutations caused by an NNRTI and other antiretroviral (ARV) medications. Additionally, Intelence also does not have CNS side effects that are characteristic of the most commonly used NNRTI on the market. Perceived downsides, however, are the known side effects of rash and nausea, as well as its BID dosing schedule. BID dosing is not expected to hamper usage dramatically, since Intelence is expected to be used primarily in treatment-experienced patients who may be taking other BID antiretroviral medications.

—Noah Pines, EVP, GfK V2, Jan. 2008

Also in the Pipeline (according to Adis R&D Insight)
No competitor compounds in phase III or pre-registration, US.

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Pharmacology
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It works by blocking RNA-dependent and DNA-dependent DNA polymerase activity of HIV-1.

Clinical Trials
Approval was based on two large randomized, controlled studies, DUET-1 and DUET-2, as well as a 24-week pooled analysis of these studies. The results of DUET-1 and DUET-2 were published separately in two articles in the July 7, 2007, issue of The Lancet, and the pooled analysis from the DUET studies was presented at the 47^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in September 2007.

Adverse Reactions
Rash (may be serious, eg, Stevens-Johnson syndrome, hypersensitivity, erythema multiforme; discontinue if occurs), GI upset, fat redistribution, immune reconstitution syndrome, lab value changes (eg, lipids, blood glucose).

Adults
Take after meals. May disperse tabs in water and drink. 200mg twice daily.

Children
Not recommended.

Precautions
Severe hepatic impairment. Pregnancy (Cat.B). Nursing mothers: not recommended.

Interactions
Concomitant tipranivir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, PIs without ritonavir (eg, atazanavir, fosamprenavir, nelfinavir, indinavir), ritonavir (600mg twice daily), NNRTIs (eg, efavirenz, nevirapine, delavirdine): not recommended. Avoid rifampin, rifapentine, St. John’s wort, carbamazepine, phenytoin, phenobarbital; rifabutin with darunavir/ritonavir. May affect, or be affected by, drugs that induce or inhibit, or that are substrates of, CYP3A4, CYP2C9, CYP2C19 (eg, azole antifungals, immunosuppressants); monitor. Potentiated by lopinavir/ritonavir. May antagonize antiarrhythmics (eg, amiodarone, bepridil, quinidine) (monitor), sildenafil. May potentiate warfarin, diazepam. May be antagonized by anticonvulsants, dexamethasone. Clarithromycin (consider azithromycin for treating MAC). Adjust statin dose (except pravastatin, rosuvastatin). Rifabutin (adjust dose with etravirine monotherapy). See literature.