China’s First Home Grown Novel HIV Drug Shoots For Prime Time

With a fast-growing HIV population and reliance on older-generation treatments, China could become the next frontier for new antiretroviral drugs. Government support might see the country’s first novel locally developed, long-lasting injectable product take on the big names in the field.

A new fusion inhibitor that prevents HIV entry into cells, albuvirtide, has reached its primary endpoint in a Phase III trial conducted in China, opening the way to the possible approval in this market of what would be the country’s first domestically developed original drug for the disease.

"The results show that albuvirtide is equivalent in efficacy to the current second-line treatment recommended by the World Health Organization [lopinavir plus ritonavir], and with a better renal safety profile," Xie Dong, chief scientific officer of developer Nanjing Frontier Biotech Co. Ltd., said in a statement.

The open-label study compared albuvirtide with lopinavir plus ritonavir in HIV-1 infected adults failing their first-line treatment. The drug was given once weekly via intravenous infusion against the primary endpoint of percentage of participants with plasma HIV-1 RNA levels suppressed to fewer than 50 copies/mL at week 48.

Albuvirtide is a synthetic peptide chemically related to Roche's Fuzeon (enfuvirtide), the only approved fusion inhibitor. However, Fuzeon must be administered by subcutaneous injection twice daily, potentially giving Frontier’s drug the edge in convenience and ease of use.

In China, providing additional treatments for HIV carriers is particularly significant, Xie said. "China lacks domestically developed innovative antiretroviral treatments. Albuvirtide is expected to provide a new option, changing the current all-oral regimen, and to provide an alternative to lifelong daily use of drugs," he added.

Development Quest

Established in 2002, the Nanjing-based firm has been on a quest to develop innovative new drugs for over a decade. The decision to devote its resources to a long-acting anti-HIV injectable drug was a “bold and forward-looking one,” general manager Wang Changjin told Scrip.

Some of the main reasons were to address poor patient compliance that have caused drug resistance issues. Most of the currently available 28 anti-HIV drugs are oral, and developing long-acting injectable therapies is a new trend.

One of the new such therapies is a combination of two long-acting injectable antiretrovirals,ViiV Healthcare's cabotegravir and Johnson & Johnson's Edurant (rilpivirine). Given once every four or eight weeks, the regimen appeared safe and well-tolerated according to results from the LATTE 2 trial presented at this year’s Conference on Retroviruses and Opportunistic Infections.

Long-acting therapies "could offer an attractive option for people with HIV facing a lifetime of antiretroviral treatment" because of such products "being more convenient and potentially improving adherence," noted Liz Highleyman in an article published on the Aidsmap website. "But the drawback is that a long-lasting drug cannot be easily removed from the body, so it is especially important to establish safety in advance."

In China, Frontier is now aiming to become the first to reach the finish line with a long-acting HIV therapy, and is planning a regulatory filing with the China FDA within 2016.

Changing Infection Routes

According to the China Centers for Disease Control, the total reported cases of HIV/AIDS in China reached 575,000, with 177,000 deaths, as of October 2015, putting the country among the top 15 nations with the largest HIV/AIDS populations.

Unlike previous years in which substance abuse accounted for the largest share of cases, 90% of new HIV cases are now spread via sexual intercourse. Men having sex with men (MSM) accounts for the majority of cases and female and senior population cases are also seeing an increase.

But due to a long-held stigma in China against MSM, the number of reported cases is thought to be lower than actual infections, which are estimated to be between three and five million, based on Frontier's estimates, Wang said.

Currently, roughly 330,000 people are receiving HIV treatments covered by China's national antiretroviral program, and the figure is expected to double to 770,000 in two to three years.

The national access program covers mainly older-generation treatments, including second-line drugs recommended by the WHO such as AbbVie Inc.' Kaletra (lopinavir plus ritonavir) and two domestic generics.

The goal for Frontier is to get albuvirtide included in second-line treatment plans and in first-line regimens for patients with conditions such as weakened renal functions and resistance to the existing first-line drug zidovudine.

Access Key To Success

But in a county like China, where many newer HIV treatments are not covered by the government's public health insurance schemes, new therapies must be affordable as well as providing convenience and ease of use.

Roche's enfuvirtide costs roughly $25,000 per year in the US, with the high cost and less convenient dosing regimen meaning that it is used primarily as a reserve therapy for patients with multidrug-resistant HIV.

ViiV's new oral integrase inhibitor Tivicay (dolutegravir) recently gained Chinese regulatory approval, and GlaxoSmithKline PLC is lowering the local price of the drug under a recent manufacturing deal between ViiV and Chinese active ingredient manufacturer [Shanghai Desano Pharmaceutical Investment Co. Ltd.] (Also see "GSK/Desano Tie-Up To Bring Large Dolutegravir Price Cuts" - Scrip, 20 Aug, 2015.).

For Frontier though, ensuring access means working with the government and physicians to include its new therapy in the national antiretroviral program. "We plan to achieve win-wins, so patients can afford it, the government can cover it, and we still have profit," Wang stated.

Young white collar HIV patients may prefer higher efficacy and favor a treatment that offers more convenience, even with a higher price, the company hopes.

"As a specialty drug maker, developing the new anti-HIV drug has [meant we] received grants from the government, enabling us to develop it all the way to the clinical stage. [But] it also needs critical disease coverage and local governments’ fiscal support, making it truly benefit patients and the society," Wang said.

The Chinese company is also looking to develop albuvirtide in selected Eastern Europe countries including Russia and Ukraine.

From the editors of PharmAsia News.