High Response Rate with Enfuvirtide (Fuzeon) Plus Darunavir (Prezista) Regardless of Existing Protease Inhibitor Resistance

Interim results from BLQ (Below the Level of Quantification), an ongoing study evaluating the use of the injectable fusion inhibitor enfuvirtide (Fuzeon, T-20) with the recently-approved ritonavir-boosted oral protease inhibitor (PI) darunavir (Prezista), in combination with other anti-HIV drugs, showed that almost two-thirds (64%) of 3-class treatment-experienced patients achieved undetectable HIV viral load (<50 copies/mL) at 24 weeks. In addition, baseline sensitivity to darunavir did not appear to influence patient response.

Preliminary results of the BLQ study were presented by Andrew Zolopa, MD, of Stanford University in a poster discussion session at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007).

Co-developed by Roche and Trimeris, enfuvirtide is the first and only fusion inhibitor commercially available for the treatment of HIV, and is also the sole approved drug in the entry inhibitor class. Ritonavir-boosted darunavir, an oral PI approved for use in treatment-experienced HIV patients, was developed by Tibotec Therapeutics. The BLQ study was sponsored by Roche and Trimeris. Patients received darunavir predominantly through co-enrollment in the darunavir compassionate use program.

"Previous studies had provided encouraging - but limited - information on the use of enfuvirtide in combination with darunavir/ritonavir," said Edwin DeJesus, MD, of the Orlando Immunology Center. "Given that attaining undetectable HIV of less than 50 copies has become the standard of care even in treatment-experienced patients, it is encouraging that so many patients can achieve this result with enfuvirtide and darunavir/ritonavir - 2 agents widely available to patients and physicians today. Even patients with significant resistance to darunavir responded well to this combination."

The BLQ Study

The BLQ study is a prospective, open-label, 24-week, single-arm, multicenter, cohort study conducted in the United States and Australia. The trial was designed to explore the impact of baseline variables - including darunavir phenotypic sensitivity (prior drug resistance) - on virological responses in highly treatment-experienced patients receiving regimens containing enfuvirtide and darunavir/ritonavir.

Patients received the approved dosages of enfuvirtide and darunavir/ritonavir, along with other anti-HIV drugs selected on the basis of individual treatment history and resistance testing.

This protocol-defined interim analysis was conducted when the first half of the total enrolled participants completed their week 24 assessments. Of 63 eligible patients enrolled, 62 had taken at least 1 dose of study medication and a safety follow-up at day 7, and were included in the safety analysis.

A total of 58 patients who received at least 1 dose of study medication and received at least 1 post-baseline efficacy assessment at week 4 were included in the intent-to-treat (ITT) efficacy analysis; 5 were excluded due to missed post-baseline assessments.

Results

• At 24 weeks, 64% of patients achieved undetectable HIV viral load less than 50 copies/mL.

• 78% of patients achieved undetectable HIV less than 400 copies/mL.

• 86% of patients achieved a viral load reduction of at least 1 log10.

• The mean reduction in HIV RNA was 2.39 log10.

• When virological response was analyzed as a function of patients' baseline phenotypic sensitivity to darunavir, the percentages of patients achieving less than 50 copies/mL were similar in the 3 groups of patients:

- 67% undetectable for patients with a low levels of resistance (fold change of less than 10);

- 70% undetectable for patients with medium levels of resistance (fold change of 10 or greater and less than or equal to 40);

- 67% undetectable for patients with high levels of resistance (fold change greater than 40).

• Treatment with enfuvirtide and darunavir/ritonavir with other anti-HIV drugs was generally well tolerated.

• 11 serious adverse events were reported in 7 patients.

• 2 of these patients discontinued therapy due to adverse events.

• 1 additional patient discontinued therapy due to an adverse event not considered to be serious.

• 1 death (unrelated to the study drugs) was reported in a patient with sepsis, worsening anemia, and worsening renal insufficiency.

Conclusion

Based on these findings, the investigators concluded, "In this sample [Expanded Access Program] population of treatment-experienced patients, virologic responses at week 24 were uniformly excellent when darunavir/ritonavir and enfuvirtide were combined with optimized background therapy in patients naive to these 2 drugs."

Orlando Immunology Center, Orlando, FL; Stanford University Medical Center, Palo Alto, CA; AIDS Healthcare Foundation, Los Angeles, CA; Synergy Hematology Oncology Med. Assoc., Los Angeles, CA; Therapeutic Concepts, Houston, TX; Trimeris, Inc., Durham, NC; Roche Laboratories, Nutley, NJ.

More Information about Enfuvirtide (Fuzeon, T-20)

More Information about Darunavir (Prezista) and Darunavir/ritonavir

08/07/07

Reference
E DeJesus, A Zolopa, C Farthing, and others. Response to darunavir/ritonavir (DRV/r) combined with enfuvirtide (ENF)-containing ARV in triple-class experienced patients was not predicted by baseline darunavir (DRV) sensitivity or viral tropism (VT): the BLQ study preliminary results. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, July 22-25, 2007. Sydney, Australia. Abstract (poster) WEPEB039.