Qilu Pharmaceutical's Entrectinib Tablets for the treatment of HIV-1 (Human Immunodeficiency Virus Type 1) infection have recently been approved for marketing in China. This marks the first generic version of the drug and is currently the only domestically produced exclusive product in China. The original drug was developed by Gilead and has not yet been approved for marketing in China, with global sales of the original drug exceeding $1.3 billion in 2023. As the first generic and exclusive product in China, the approval and launch of Qilu Pharmaceutical's Entrectinib Tablets bring new treatment options to Chinese patients and add new variables to the competitive landscape. Amid a scarcity of domestically produced innovative anti-HIV drugs, which other companies in China are investing in the research and development of innovative anti-HIV medications?
Qilu Pharmaceutical Secures Exclusive First Generic of Entrectinib Capsules
Entecavir, Rilpivirine, and Tenofovir Alafenamide Tablets are a triple combination formulation of Entecavir, Rilpivirine Hydrochloride, and Tenofovir Alafenamide Fumarate. Entecavir is a nucleoside reverse transcriptase inhibitor that blocks the synthesis of viral DNA chains. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that inhibits viral replication by non-competitively inhibiting HIV-1 reverse transcriptase and exhibits broad-spectrum antiviral activity against various HIV-1 subtypes. Tenofovir Alafenamide is converted into its active form, Tenofovir, in the body, and then further transformed into Tenofovir Diphosphate through phosphorylation, inducing termination of viral DNA chain replication. The combination of these three drugs has proven efficacy and is a guideline-recommended antiviral treatment regimen for adult and adolescent patients who are new to therapy. The single-tablet regimen is more convenient to administer, requiring only one tablet per day, which helps reduce the medication burden on patients and improve adherence.
In 2023, Gilead's original drug Odefsey achieved global sales of $1.35 billion, but it has not yet been launched in China. According to the information disclosed by Qilu Pharmaceutical, during the research and development process, researchers successfully resolved multiple technical challenges. They systematically compared the quality of their self-produced version with the original product, completed human bioequivalence trials, and ensured that the self-produced version is equivalent in quality, safe, and clinically interchangeable with the original product.
Qilu Pharmaceutical has launched products such as Tenofovir Disoproxil Fumarate Tablets, Emtricitabine Tenofovir Tablets, and Emtricitabine Capsules in the anti-AIDS field.
AIDS, or Acquired Immune Deficiency Syndrome, is caused by the infection of Human Immunodeficiency Virus (HIV). HIV attacks the human immune system, primarily targeting the most crucial CD4 T lymphocytes in the immune system, destroying a large number of these cells, resulting in the loss of immune function, increased susceptibility to various diseases, occurrence of malignant tumors, and a high mortality rate.
Thanks to the implementation of China's "Four Frees and One Care" policy, HIV infection has gradually transformed from a fatal disease into a preventable and controllable chronic infectious disease. The "2022-2027 China Anti-AIDS Drug Industry Development Monitoring and Strategic Planning Report" released by Huajing Industrial Research Institute shows that among Chinese HIV carriers, the proportion of free drugs is 58.2%, medical insurance drugs account for 20%, and self-paid drugs account for 21%.
From a global market perspective, innovative anti-AIDS drugs have achieved impressive sales. Gilead, which dominates over half of the global anti-AIDS drug market, reported combined sales of its anti-AIDS product portfolio exceeding $18.7 billion, marking a 6% year-on-year increase. Its star anti-AIDS product, Biktarvy, generated sales surpassing $10 billion in both 2022 and 2023. GlaxoSmithKline, Johnson & Johnson, Bristol-Myers Squibb, and Merck are also key players in the global anti-AIDS field.
However, the overall price of imported anti-AIDS drugs is higher than that of domestically produced drugs in China. The number of single-tablet combination formulations available to Chinese AIDS patients is too low to meet clinical needs. The approval and market entry of generic drugs can supply the market at more affordable prices, thereby improving drug accessibility and benefiting more patients.
National Policy Encourages Innovation and R&D
Currently, the anti-AIDS drug market in China is dominated by imported drugs and domestically produced generic drugs. The imported drug market is occupied by a few companies such as Gilead, GlaxoSmithKline, and Merck, which account for approximately 80% of the market share, while more than 40 local enterprises, including Qilu Pharmaceutical and Betta Pharmaceuticals, have ventured into the generic drug sector.
To encourage the development of innovative domestic drugs, in December 2017, the former China Food and Drug Administration issued and implemented the "Opinions on Encouraging Innovation in Pharmaceuticals through Priority Review and Approval." It mentioned that applications for the registration of HIV/AIDS prevention and treatment drugs could be included in the priority review and approval scope to accelerate the market entry of domestically produced innovative HIV/AIDS drugs. In the same year, under the national "13th Five-Year Plan" Major New Drug Development Project, Frontier Biopharmaceuticals was specifically appointed to lead a collaboration with Ascletis, Adcare Pharma, Baker Bio, and Desano Pharmaceuticals to carry out the "Research and Development of Innovative Drugs for HIV/AIDS Treatment and Clinically Urgent Medications."
A reporter from The Beijing News searched the Wisdom Tooth Global New Drug Intelligence Database using "HIV infection" as the keyword. As of July 18, a total of 280 drugs worldwide have been approved for clinical trials, or have been submitted for approval / approved for marketing. Among them, 41 drugs have been approved for marketing in China. From the enterprise perspective, GSK, Viatris, Gilead, Merck, and Johnson & Johnson have the highest number of approvals. AdEra Pharma has two drugs approved for marketing (produced in China), both of which are self-developed Class 1 innovative drugs.
In addition, there are 14 drugs in Phase I clinical trials in China, 9 in Phase II clinical trials, 3 in Phase III clinical trials, and 1 drug, Gilead's Lenacapavir, is under submission for marketing approval. This drug was approved for marketing in the United States in December 2022 for use in combination with other antiretroviral drugs to treat adult patients with multidrug-resistant human immunodeficiency virus (HIV) infection.
According to statistics from a reporter of the New Beijing News, so far, there are four domestically produced innovative anti-AIDS drugs approved for marketing in China. The drug Aibohuibet (Aibovir) developed by Frontier Biotech, which was approved for marketing in July 2018, is China's first original Class 1 new anti-AIDS drug and also the world’s first long-acting fusion inhibitor. In June 2021, Aino Wei Lin (Ainuovir), developed by Aidi Pharmaceuticals, was approved for marketing, becoming the second domestically self-developed Class 1 new anti-AIDS drug. One month later, Azvudine Tablets developed by Genuine Biotech had its anti-AIDS indication conditionally approved for marketing. In December 2022, Aino Mitui Tablets were approved, becoming the fourth domestically produced innovative anti-AIDS drug in China.
Driven by policy incentives, an increasing number of companies are joining the effort to advance the research and development of innovative anti-AIDS drugs produced in China. According to incomplete statistics from reporters at The Beijing News, more than 20 local companies are involved in the development of innovative anti-AIDS drugs, including not only Adva Biopharmaceuticals, Genuine Biotech, and Frontier Biotechnologies, but also Hengrui Medicine, Qingfeng Pharmaceutical, Staidson, Clover Biopharmaceuticals, Hansoh Pharma, and Chipscreen Biosciences.
As the exclusive first-to-market generic drug, Enquilitib Pinodazole Tablets face no competition from original research drugs or generics of the same variety. However, they still encounter fierce competition from other imported and domestically produced innovative anti-AIDS drugs. Imported brands have already established high brand recognition and patient loyalty in the market, while domestic innovative drugs also possess unique therapeutic advantages and innovation, making them strong competitors. For Qilu Pharmaceutical to gain a larger market share is no easy task. Nevertheless, it is worth anticipating that as the R&D capabilities of local pharmaceutical companies continue to improve, more high-quality and affordable drugs will be approved and launched in China's anti-HIV drug market in the future, providing patients with more treatment options.
Reporter Wang Kala of The Beijing News
Proofread by Baoqing Liu