[e-med] Darunavir, nouvel ARV qui vient d'être autorisé par la FDA

["ReMeD" <c.bruneton@remed.org>]

[on n'arrête pas le progrès... un nouvel ARV vient d'être autorisé par la 
FDA (ESA),  darunavir (DCI) ou le Prezista, un inhibiteur de protease actif 
là où les virus sont résistant aux autres inhibiteurs de protease. Et le 
prix s'élève à 25 dollars par jour aux USA... CB]

****************

Date: Mon, 03 Jul 2006 12:36:46 -0400
From: Mike Palmedo <mpalmedo@cptech.org>
To: ip-health@lists.essential.org
Subject: [Ip-health] AIDS Treatment News on approval and pricing of new
protease inhibitor

http://www.aidsnews.org/2006/06/prezista-approved.html

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

AIDS Treatment News
by John S. James

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 http://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,
http://www.aidsmeds.com/news/am20060627.html
Also see the lead article in the latest issue of Project Inform
Perspective, (published before the price was set),
http://www.projectinform.org/pip/41/pip41.html (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
http://www.champnetwork.org/index.php?name=tibotec-letter

References

1. "Tipranavir Study Halted in Treatment-Naive," by Keith Alcorn,
Aidsmap, June 21, 2006,
http://www.aidsmap.org/en/news/1F626F94-0A95-485B-84F3-D4C095B73CB2.asp
(It may be easier to go to http://www.aidsmap.org and type the first
three words of the title into the search box at the upper right of the
page).