LATTE-2 Study Results Favorable at 160 Weeks

ViiV Healthcare announced new favorable 3-year results for the phase 2b LATTE-2 study of their long-acting 2-drug injectable regimen for HIV, indicating the combination drug maintained high rates of virological response, long-term durability of the response, and good overall tolerability at 160 weeks. The results were presented at the HIV Glasgow Drug Therapy Meeting, which was held October 28-31, 2018 in Glasgow, Scotland.

LATTE-2 is a phase 2b, multicenter, parallel-group, open-label study of the long-acting 2-drug injectable regimen of cabotegravir and rilpivirine in treatment-naive HIV infected adults. The new data presented include the 3-year results from the investigation.

“The LATTE-2, 3-year data show cabotegravir and rilpivirine as a long-acting injectable regimen may provide an alternative to daily pills, reducing the number of annual doses from 365 to 12. It is encouraging to see these long-term results," John C. Pottage, Jr, MD, Chief Scientific and Medical Officer of ViiV Healthcare said in a recent statement.

Cabotegravir is being evaluated as a long-acting formulation for intramuscular injection and as a once-daily oral tablet for use as a lead-in to establish the tolerability of cabotegravir prior to long-acting injection.

Rilpivirine is a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of HIV in combination with other antiretroviral agents in treatment-naïve adult patients with a viral load of <100,000 HIV RNA copies/mL. Long-acting rilpivirine is not approved by the US Food and Drug Administration or regulatory authorities anywhere in the world.

In the LATTE-2 trial, patients were first put on a regimen of oral cabotegravir and abacavir/lamivudine for 20 weeks. After the induction period, suppressed patients were randomized 2:2:1 to receive either the long-acting injectable cabotegravir and rilpivirine every 4 or every 8 weeks, or to continue the 3-drug oral regimen. Patients on the long-acting regimen were extended through to 160 weeks and patients on the oral regimen were given the option of transitioning to the regimen every 4 or every 8 weeks at week 96.

At 160 weeks, 104 of 115 participants (90%) and 95 of 115 participants (83%) receiving the injectable regimen, every 8 and 4 weeks respectively, remained virally suppressed. Of the patients on the oral comparator arm who chose to switch to the injectable regimen at week 96, 33 of 34 participants (97%) and 10 of 10 participants (100%) remained virally suppressed on every 8 and 4-week dosing, respectively.

Through Week 48, 2 participants developed protocol defined virologic failure (PVDF) on the every 8-week dosing arm, 1 with treatment-emergent, NNRTI and integrase inhibitor resistance. No additional PVDF cases were observed in the study between weeks 48 and 160.

Injection site reactions were reported in a majority of participants through week 160, 85% of which were mild and 14% were moderate. However, 87% of these reactions were resolved within 7 days. Three of the 274 participants experienced injection site reactions that led to discontinuation through week 160.

Excluding injection site reactions, the most common adverse events were nasopharyngitis (38%), diarrhea (22%) and headache 22%. In total, 3 of 115 patients in the 8-week group, and 12 of 115 participants in the 5-week group had adverse events leading to withdrawal.

Rilpivirine is not recommended for patients under 12. Additionally, the most common side effects include depression, headache, insomnia and skin rashes. Hepatic adverse events have been reported and patients with underlying disease including hepatitis B or C may be at an increased risk. Redistribution and/or accumulation of body fat have been observed as well as autoimmune disorders including Graves disease, polymyositis, and Guillain-Barré syndrome.