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Prezista (Darunavir, TMC-114) Approved; May Be Important Treatment Advance

By John S. James

June 29, 2006

Summary: A major new antiretroviral has been approved, for patients resistant to more than one protease inhibitor. There is no information yet on risk/benefit compared to standard treatments for first-line use. Tibotec, which developed the drug and is now part of Johnson & Johnson, showed price restraint and avoided setting a new record high price, which other companies have done.

Prezista (also called darunavir, or TMC-114), a new protease inhibitor active against many of the viruses resistant to other protease inhibitors, was approved by the FDA on June 23 "for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor." In hard-to-treat patients already highly resistant to other antiretrovirals, 70% of patients taking Prezista together with other HIV treatments had a virologic response at week 24, vs. 21% of patients on other treatments only, according to the FDA's analysis.

Prezista must be taken with a small dose of ritonavir, and also with food (the type of food is not important). Otherwise, the level of Prezista in the blood will be too low, greatly increasing the risk of viral resistance. Prezista is supplied as 300 mg tablets; the usual adult dose is two of these tablets plus 100 mg of ritonavir, taken twice a day with food (a total of 4 Prezista tablets and two 100-mg ritonavir tablets per day).

While Prezista was designed to overcome viral resistance to other protease inhibitors, resistance to the drug itself can develop. Some of the patients in the trials already had cross resistance to Prezista when the trial began (due to their extensive resistance to other protease inhibitors), and this resistance got worse as they used the drug -- showing the importance of having more than one active antiretroviral, instead of introducing new drugs one by one as they become available, and then often losing them to resistance.


Price and Access -- An Activist Victory

Tibotec, a Belgian company that specializes in designing new drug molecules engineered to prevent resistance, developed Prezista. Tibotec did not have the money to complete the very expensive large clinical trials, so it was acquired by Johnson & Johnson, which provided the money and was able go get the trials moving rapidly, resulting in the current approval.

Shortly after approval, the price was set at $25 a day (wholesale acquisition price) -- at the low end of the last three protease inhibitors approved (the ritonavir will cost extra). This was a clear change from the recent past, where each new drug set a new price record. Companies have called the routine escalation "value benchmark" pricing, saying that the new drug was more valuable so it justified a higher price. Without the activism noted below, the price could have been more than twice as high -- preventing the drug from ever being widely used for first-line treatment, where the need is not immediate and desperate.

In fact, each antiretroviral has complex advantages and disadvantages; most new ones are more equivalent than superior to existing treatments, except for a small fraction of patients who strongly benefit -- the advantage of having more choice instead of less. And cumulatively, the steady price escalation has caused drugs to be used irrationally because patients and public programs cannot afford reliable supplies, leading to unplanned interruptions and people not receiving the medication they need. High prices also increase incentives for private insurance and public programs to use various means of restricting access, depriving doctors and patients of choice, especially when they want to use a treatment off-label (prescribe an approved drug for a use not specifically approved by the FDA, universally recognized as an important part of medicine since companies cannot possible run clinical trials for all appropriate uses, and therefore the FDA cannot approve them. But for private and public insurance, off-label status provides an excuse not to pay for more expensive treatment.)

Before the approval of Prezista and long before the price was announced, activists loosely organized as the Fair Pricing Coalition began a campaign to talk to the leadership of Tibotec Therapeutics about the "growing national and international crisis in the cost of health care" and the need for corporate responsibility. Hundreds of community organizations and individuals signed a consensus letter to Tibotec for pricing that is cost neutral, instead of pushing up the cost of treatment with every new drug. Tibotec responded, and broke the unsustainable cycle of big price increases every time.

The lower price could well be in the company's financial interest, by allowing first-line use if the drug proves suitable -- especially important now that its rival Aptivus (tipranavir) does not seem to be working well as a first-line treatment, with a clinical trial stopped because of performance that appears slightly inferior to a good standard treatment based on Kaletra.1 We have not seen an analysis of that trial, but the general picture is that while a very good resistance profile (such as with Aptivus, or Prezista) is of course a benefit in first-line use because it is likely to extend the success of the regimen, the overall performance of a drug depends on many factors, including tolerability of side effects so that patients can continue taking it. First-line use (by patients who have never taken antiretrovirals) must compete against fairly good standard treatment options. Since Prezista was fortunately tested first for those who needed it most, we do not have such comparisons yet.


For More Information

For more information about Prezista, one place to start is the PREZISTA (darunavir) Tablets -- Patient Information sheet, which should be included with each bottle of the tablets. It can also be found on the Web, probably at www.prezista.com/ (the site was not ready when this issue went to press).

For much more detail see the prescribing information for physicians, which should also be on that site. Incidentally, the information for patients is included as the last six or so pages of the document for physicians.

For information on the pricing campaign, see "Activists Say New HIV Drug Price Encouraging," by Tim Horn.

Also see the lead article in the latest issue of Project Inform Perspective (published before the price was set; do not write to Tibotec as directed; that campaign is over as the company has already announced a price much lower than what was feared). The excellent consensus statement to Tibotec, and lists of signers, is at www.champnetwork.org/index.php?name=tibotec-letter.


References

  1. "Tipranavir Study Halted in Treatment-Naive," by Keith Alcorn, Aidsmap, June 21, 2006.

Copyright 2006 by John S. James. See "Permission to Copy" at: www.aidsnews.org/canhelp/.




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