On February 16, Tibotec Pharmaceuticals, Ltd. announced that the European Commission has granted conditional marketing authorization for the company's protease inhibitor darunavir (Prezista; previously known as TMC114). Darunavir was approved by the U.S. Food and Drug Administration (FDA) in June 2006. Approval was based on safety and efficacy data from the POWER 1, 2, and 3 studies.

Following are excerpts from Tibotec's press release announcing the approval:

Anti-HIV Medication Prezista Receives Conditional Marketing Authorization in the European Union

Centralised procedure authorises use in all 27 EU member states, plus others

Cork, Ireland, February 16, 2007 - Tibotec Pharmaceuticals, Ltd. announced today that the European Commission has granted a conditional marketing authorisation for PREZISTA (darunavir, also known by the investigational compound number TMC114), a protease inhibitor for the treatment of HIV-1 infected patients.

This decision by the European Commission through a centralised procedure, signifies that the treatment is authorised for use in the European Union (EU), valid in all 27 EU member states. A conditional marketing authorisation was granted to PREZISTA, taken in combination with ritonavir and other antiretroviral medicinal products, because of its benefits for HIV-1 infected patients, however, more evidence is yet to be provided. Additional safety and efficacy data will need to be submitted to the EMEA [European Agency for the Evaluation of Medicinal Products] annually until full authorisation is granted.

The timing of the availability of the product will be decided in discussions with national authorities and will vary from country to country.

PREZISTA, co administered with 100 mg ritonavir, is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV 1) infection in highly pre treated adult patients who failed more than one regimen containing a protease inhibitor (PI) [1].

The approval was based on 24-week safety and efficacy data from POWER 1 and POWER 2, two ongoing, randomised, controlled trials involving 255 treatment-experienced adults. The results were supported by a 24-week analysis of the open label trials (POWER 3 analysis) of 327 patients who were initiated at the recommended dose of 600 mg PREZISTA boosted with 100 mg ritonavir twice daily [2].

POWER 1 and 2 Efficacy Results

In a pooled analysis of the POWER 1 and 2 studies, following 24 weeks of treatment [2]:

• 70 percent of 131 patients in the PREZISTA arm had a virologic response compared to 21 percent of 124 patients in the control group. Virologic response is defined as a decrease in viral load of at least 1.0 log10 (90 percent reduction) from baseline.

• Three times as many patients in the PREZISTA arm (45 percent) achieved an undetectable viral load compared with patients in the investigator-selected PI arm (12 percent). Undetectable was defined as HIV RNA of less than 50 copies/mL.

• The mean increase in CD4 cell counts from baseline was five times higher in the PREZISTA group than in the control group (92 cells/mm3 vs.17 cells/mm3, respectively).

POWER 3 Efficacy Results

The European Commission decision also was based on supportive data from the POWER 3 analysis, a non-randomised, open-label analysis of treatment-experienced patients similar to those of POWER 1 and POWER 2 and who received darunavir/rtv (600mg/100mg twice daily). Data from this large cohort (n=327) showed that after 24 weeks [2]:

• 66 percent of patients achieved a reduction in viral load of 1.0 log10 or more, vs. baseline.

• 43 percent of patients reached undetectable virus levels (less than 50 HIV RNA copies/mL).

Long-Term Results

Additionally, the product labelling includes supportive 48-week long term efficacy data from the pooled analysis of POWER 1 and POWER 2 in treatment experienced patients who received darunavir /rtv (600mg/100mg twice daily). The 48-week analysis indicates that [3]:

• 61 percent of patients achieved a reduction in viral load of 1.0 log10 or more, vs. baseline.

• 45 percent of patients reached undetectable virus levels (less than 50 HIV RNA copies/mL).

"The approval of PREZISTA marks an important step in the management of highly treatment-experienced patients," said Professor Margaret Johnson, Chair of the British HIV Association (BHIVA) Executive Committee and Clinical Director of HIV/AIDS Services, Royal Free Hampstead, NHS Trust. "Finding additional therapy options for highly treatment-experienced patients is one of the greatest challenges in HIV care today, as many of these people are currently on treatments which, are either failing or have already failed. The data presented so far is promising and PREZISTA will provide a vital new option for these patients."

"The approval of PREZISTA reflects the ongoing commitment of Tibotec to delivering therapeutic approaches that help people with HIV who have unmet needs," said Roger Pomerantz, MD, President of Tibotec.

Important Safety Information

PREZISTA does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

In the registrational studies, PREZISTA was generally well tolerated versus the investigator selected PIs. The majority of the adverse reactions reported in this data during treatment with PREZISTA co administered with 100 mg ritonavir twice daily were mild to moderate in severity. The most frequently reported moderate to severe adverse reactions were diarrhoea (2.6%), vomiting (2.2%) and hypertriglyceridaemia (2.0%) [4]. The most commonly reported adverse reactions of any grade were nausea (7.2%), diarrhea (6.6%) and headache (3.3%). Skin rash can also appear but this is usually mild to moderate [5]. One percent of patients discontinued treatment due to adverse events [4]. People who are allergic to darunavir or any of its ingredients, or ritonavir should not take PREZISTA.

Before taking PREZISTA, patients should tell their doctor if they have any medical conditions, including diabetes, liver problems, haemophilia, or allergy to sulfa medicines and should tell their doctor if they are pregnant or planning to become pregnant, or are nursing. PREZISTA should not be used in patients with severe liver problems.

There were some relevant drug-drug interactions [6] with other medications commonly used in HIV patient populations, such as other antiretroviral medications, proton pump inhibitors, and H2 receptor antagonists. Patients should talk to their healthcare provider about all the medicines they are taking or plan to take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Please see full Product Information for more details.

About PREZISTA

PREZISTA was developed by Tibotec Pharmaceuticals Ltd. Tibotec, a division of Janssen-Cilag, will commercialise the product in Europe, Russia, Switzerland and other countries. The marketing authorisation holder for PREZISTA in Europe is Janssen-Cilag International NV. In the U.S., it is marketed by Tibotec Therapeutics, a division of Ortho Biotech Products, L.P. In Canada, it is marketed by Tibotec, a division of Janssen-Ortho Inc.

PREZISTA/ritonavir is currently in Phase III comparative clinical trials in treatment-naïve (ARTEMIS) and less treatment-experienced patients (TITAN) versus Kaletra (lopinavir/ritonavir). In Phase III studies known as DUET 1 and 2, darunavir is being studied with an investigational NNRTI, TMC125, in heavily treatment-experienced patients. Clinical studies on the use of the product in HIV-infected paediatric patients are also ongoing.

For further information, please visit www.tibotec.com.

References:

1. Prezista (darunavir) Summary of Product Characteristics EU (Page 2).
2. Prezista (darunavir) Summary of Product Characteristics EU (Page 15).
3. Prezista (darunavir) Summary of Product Characteristics EU (Page 16).
4. Prezista (darunavir) Summary of Product Characteristics EU (Page 11).
5. Prezista (darunavir) Summary of Product Characteristics EU (Page 32).
6. Prezista (darunavir) Summary of Product Characteristics EU (Pages 5-10).

02/20/07

Source

Tibotec Pharmaceuticals. Anti-HIV Medication Prezista Receives Conditional Marketing Authorization in the European Union. Press Release. February 16, 2007.