BARCELONA (July 9, 2002) – Roche today announced encouraging results of four new studies examining "double boosting" – an investigational treatment strategy which combines a twice-daily regimen of saquinavir (1000 mg) with Kaletraâ (lopinavir 400 mg/ritonavir 100 mg) – in treatment-experienced HIV patients. Data from 4 studies reported at the conference suggest, this approach provides potent HIV suppression and improvement in CD4-immune status even in heavily pretreated patients.

"The dramatic results from these studies with a boosted saquinavir dose of 1000mg could offer a new treatment strategy for patients who are heavily pre-treated and running out of options," said Dr Bonaventura Clotet, Head of HIV Section, Hospital Germans Trias i Pujol, Barcelona, Spain. "As the problem of growing resistance poses a major challenge, double-boosted protease inhibitor regimens can help buy more time for patients who have become resistant to available treatments."

Co-administering protease inhibitors with low doses of ritonavir, another protease inhibitor, is an investigational treatment strategy known as "boosting." By using low, "non-therapeutic" doses of ritonavir, the metabolism of other protease inhibitors, such as saquinavir, can be inhibited, resulting in higher and more consistent levels of the "therapeutic" protease inhibitor. Since Kaletra is a co-formulation of lopinavir and low-dose ritonavir, dosing saquinavir with Kaletra could boost levels of both lopinavir and saquinavir.

Saquinavir with Kaletra in Heavily Treatment-Experienced PatientsThe first study examined treatment-experienced patients who had become either resistant or intolerant to nucleoside analogue therapy. Dr Schlomo Staszewski and colleagues from the HIV Clinical Research Unit at the Goethe-Universität in Frankfurt evaluated patients after switching to a nucleoside-free therapy with the double-boosted saquinavir/Kaletra regimen. After 14 weeks, CD4 cell count rose from 198 to 291 cells/mm3, and the amount of HIV virus dropped substantially by 2.86 log10 copies/ml.

A second study, conducted by Dr Graham Smith and colleagues from the Montréal Chest Institute evaluated high risk, advanced HIV-infected patients who had developed resistance to all three HIV drug classes. After 48 weeks using the double-boosted saquinavir regimen, the average decrease in viral load was 1.1 log and the mean CD4 cell count increase was 100 cells/mm3.

The third study examined heavily treatment-experienced patients who failed more than two antiretroviral regimens. At baseline, patients were divided into two groups: twenty-four patients initiated treatment with saquinavir and Kaletra plus 3TC, abacavir and ddI immediately, while 22 patients underwent a three month structured treatment interruption before beginning treatment. After 48 weeks of treatment, 45 percent of patients starting treatment without interruption achieved plasma viral loads of less than 80 copies/mL; 50 percent of patients interrupting therapy also achieved this level of suppression. A mean CD4+ increase of 73 and 31 cells/mm3 was observed among patients beginning treatment immediately and after interruption, respectively. Overall, the number of prior regimens, CD4+ count, drug resistance mutations or whether an STI was taken at baseline was not associated with the virological response.

Comparing Saquinavir or Amprenavir with Kaletra at 48 Weeks

A prospective, open-label trial, directly compared either saquinavir or amprenavir in combination with Kaletra. After 48 weeks of treatment, 40 percent of patients taking saquinavir with Kaletra (n=23) and a combination of NRTIs achieved undetectable HIV viral loads (less than 500 copies/mL), while 21 percent of patients on amprenavir-based therapy (n=19) achieved a similar result. Furthermore, 86 percent patients of continuing saquinavir-based treatment to 48-weeks had achieved HIV-RNA reductions of at least 1.0 log10 copies/mL, while 70 percent of patients on the amprenavir arm achieved the same reduction. Patients recruited to the study had baseline median HIV RNA levels of 5.55 log10 and a mean CD4+ count of 93 cells/mm3; 64 percent of patients also had a prior AIDS-defining experience. No treatment-limiting toxicity was identified in either arm of the study.

More about saquinavirSaquinavir is a member of the class of anti-HIV drugs known as protease inhibitors (PIs). PIs block a part of the HIV reproduction process involving the HIV protease, thus preventing the formation of new infectious HIV particles. Saquinavir is almost always used in combination with at least two other anti-HIV drugs and has been shown to significantly improve survival and reduce the occurrence of AIDS-defining events for people infected with HIV. Saquinavir is not a cure for HIV.

Boosting saquinavir with low doses of ritonavir allows more saquinavir to be absorbed into the blood and keeps saquinavir in the body for longer. The benefit for patients is that using this approach it is possible to reduce the dosing frequency together with the required number of capsules while still maintaining therapeutic drug levels.

In June of 2002 the Committee for Proprietary Medicinal Products (CPMP) granted a positive opinion for both INVIRASE™ (saquinavir hard gel capsules) and FORTOVASE™ (saquinavir soft gel capsules) to include co-administration with a low dose of ritonavir for the treatment of human HIV. The corresponding Commission Decision for the dosage schedule (1000mg saquinavir BID in combination with ritonavir 100mg BID) is expected by the end of August 2002.

The new schedule allows for the use of both saquinavir formulations, INVIRASE™ and FORTOVASE™. The new saquinavir/ritonavir schedule is also recommended in the new draft WHO guidelines, "Scaling up antiretroviral therapy in resource limited settings: Guidelines for a public health approach".About Roche

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