GSK Submits NDA for Doravirine/Lamivudine Fixed-Dose Combination HIV Therapy in China

On January 8, the CDE website showed that GSK/ViiV’s imported new drug “Dolutegravir and Rilpivirine Tablets” had its marketing application accepted. This drug is a novel dual-combination therapy for HIV.

AIDS is a severe autoimmune disease caused by the retrovirus HIV. Since its first discovery in 1981, it has become a major global public health issue. However, the disease cannot yet be completely eradicated, and patients require lifelong medication. Current anti-HIV drugs mainly include CCR5 antagonists, fusion inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. To avoid drug resistance resulting from monotherapy, clinical practice predominantly employs combination therapy using three or more of the aforementioned drugs.

Among the top 100 global pharmaceutical products by sales in 2019, HIV medications accounted for eight positions. Gilead Sciences led the field with five Top 100 HIV drugs: Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), Truvada (emtricitabine/tenofovir disoproxil fumarate), Odefsey, and Descovy. Johnson & Johnson and GSK each had one and two entries, respectively: Prezista/Prezcobix (darunavir/darunavir with cobicistat) from J&J, and Tivicay (dolutegravir) and Triumeq (dolutegravir/lamivudine/abacavir) from GSK. Overall, dual- and triple-drug combination regimens predominated.

The dolutegravir/rilpivirine tablets submitted for marketing approval in this application are a novel two-in-one fixed-dose combination drug for HIV, comprising dolutegravir (50 mg) and rilpivirine (25 mg). Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) that blocks the integration of viral DNA into host CD4+ cells by HIV. Rilpivirine (RPV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that non-competitively inhibits HIV-1 reverse transcriptase, thereby suppressing viral replication.

Dolutegravir/rilpivirine, as a long-term maintenance therapy, is indicated for adults with HIV-1 who have achieved virologic suppression (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months, have no history of virologic failure, and have no known or suspected resistance mutations to any non-nucleoside reverse transcriptase inhibitor (NNRTI) or integrase strand transfer inhibitor (INSTI). The drug was approved by the U.S. Food and Drug Administration (FDA) in November 2017. According to the Insight database, its global sales reached $468 million in 2019.

Currently, multiple fixed-dose combination HIV medications have also been approved in China. These dual-drug combinations include ViiV Healthcare’s abacavir/lamivudine tablets, Gilead’s emtricitabine/tenofovir disoproxil fumarate tablets and emtricitabine/tenofovir alafenamide tablets, Janssen (Belgium)’s darunavir/cobicistat tablets, and GlaxoSmithKline’s zidovudine/lamivudine tablets, among others.

However, new HIV drugs in China are still predominantly imported. Data from the Insight database shows that among new chemical drugs with indications for AIDS, 38 products are imported, while only 10 are domestically produced. Among the domestic products, only Albuvirtide by Frontier Biotechnologies has been approved for marketing. Additionally, Azvudine by True Biopharma and ACC007 by Aidi Pharmaceutical have submitted marketing applications, while the rest are still in clinical stages.

From the Insight database (http://db.dxy.cn/v5/home/)