Single Tablet Regimen for HIV Studied in Women and in Virologically Suppressed Patients With Known Resistance

Findings from a phase 3 trial demonstrated the effectiveness of switching to bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets (B/F/TAF) (Biktarvy, Gilead Sciences) in women, and a second phase 3 trial evaluated the potential for the single, combination tablet regimen to be an effective treatment option in virologically suppressed patients with known resistance to nucleotide or nonnucleotide reverse transcriptase inhibitors (NRTIs or NNRTIs). ¹

The use of B/F/TAF in patients with known drug resistance is investigational. Data from the 2 trials were recently presented at the 10^th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City.¹

Approved by FDA earlier this year, the B/F/TAF regimen is indicated for the treatment of adults with HIV-1 who have no history of antiretroviral therapy (ART), or to replace a current ART regimen in those who have achieved virologic suppression.² The use of B/F/TAF in patients with known drug resistance is investigational and has not been determined to be safe or efficacious nor is it approved by the FDA for that indication.¹

On June 18, 2019, the FDA approved labeling revisions to Gilead’s B/F/TAF, expanding the patient population to include HIV-1 infected pediatric patients weighing at least 25 kg, or 55 lbs. Gilead’s B/F/TAF product has a Boxed Warning in its United States product label regarding the risk of post-treatment acute exacerbation of hepatitis B. ¹

According to data presented by Gilead at IAS 2019, the MOAB0106 study was an international multicenter, randomized, open-label Phase 3 trial that evaluated 470 virologically suppressed women on a baseline regimen of either elvitegravir/cobicistat/F/TAF; 150/150/200/10 mg (Genvoya, Gilead), elvitegravir/cobicistat/F/TDF (150/150/200/300 mg) or atazanavir+ritonavir+F/TDF (300+100+200/300 mg) who switched 1:1 from these baseline regimens to B/F/TAF. The primary endpoint for this study demonstrated noninferior maintained virologic suppression with a low frequency of serious adverse events and no emergent resistance at week 48. All participants, including those on baseline regimens, switched to B/F/TAF through week 96. ¹

At week 96, 99.5% of the studied women who received B/F/TAF throughout the study duration and 98.5% of women who switched to B/F/TAF at week 48 maintained virologic suppression (missing=excluded; M=E), with no development of treatment-emergent resistance. B/F/TAF was also shown to be well-tolerated with low frequencies of serious adverse events. ¹

“Despite the fact that women account for the majority of new HIV infections globally, they remain largely underrepresented in HIV clinical trials,” said Cissy Kityo, MD, Executive Director, Joint Clinical Research Centre in Uganda, and lead study investigator, in a prepared statement. ¹ “The findings from this study conducted exclusively in women yield important long-term data on the safety, tolerability and efficacy of Biktarvy in this important patient population.”

The MOAB0105 study evaluated a switch to a single-tablet B/F/TAF regimen from dolutegravir (DTG) plus emtricitabine and either tenofovir alafenamide or tenofovir disoproxil fumarate (F/TAF or F/TDF). An ongoing, randomized, double-blinded Phase 3 study, MOAB0105 evaluated 565 virologically suppressed adults who switched 1:1 from a regimen of DTG+F/TAF (50+200/25 mg) or DTG+F/TDF (50+200/300 mg) to DTG+F/TAF or Biktarvy for 48 weeks. ¹

Unlike previous studies — which excluded participants with known resistance – participants in the MOAB0105 study with prior resistance to NRTIs, NNRTIs and/or protease inhibitors (PIs) could enroll. Only those participants with documented integrase inhibitor resistance were excluded, and 24% of participants had resistance to NRTIs. The study’s primary endpoint was the proportion of participants with HIV-1 RNA ≥ 50 c/ml at week 48. ¹

At week 48, 0.4% (n=284) of participants on B/F/TAF had HIV-1 RNA ≥ 50 c/ml, compared to 1.1% of participants on DTG+F/TAF (n=281) (snapshot algorithm), demonstrating noninferiority. In addition, at week 48, no treatment-emergent resistance was detected, and no participants with pre-existing NRTI resistance mutations had HIV RNA >50 c/mL. ¹

Gilead Sciences, Inc. has entered into a licensing agreement with DURECT Corporation to become the sole developer and seller of an injectable, long-acting HIV product.³

The multimillion-dollar agreement grants Gilead access to DURECT’s SABER technology. SABER (sucrose acetate isobutyrate extended release) is a patented technology that sustains release for long-term injectable products. Currently, SABER is the base for POSIMIR, which is a bupivacaine extended release solution, according to a press release.³

The 2 pharmaceutical companies will also collaborate with each other on developmental activities with funding from Gilead.³

References

• Gilead Presents New Data on Biktarvy® for the Treatment of HIV in Women and in Virologically Suppressed Patients With Known Resistance [news release]. Foster City, CA; July 22, 2019: Gilead Sciences Inc. https://www.businesswire.com/news/home/20190722005472/en. Accessed July 29, 2019.
• Rosa K. CROI 2019: Bictegravir Single-Dose Combo As Safe, Effective As DTG/ABC/3TC. Pharmacy Times. https://www.pharmacytimes.com/resource-centers/hiv/croi-2019-bictegravir-singledose-combo-as-safe-effective-as-dtgabc3tc/. Published March 7, 2019. Accessed July 29, 2019.
• DURECT and Gilead Enter into License Agreement for Long- Acting HIV Investigational Product Cision PR Newswire website. Published Jul 22, 2019. https://www.prnewswire.com/news-releases/durect-and-gilead-enter-into-license-agreement-for-long-acting-injectable-hiv-investigational-product-300888384.html Accessed Jul 22, 2019