5 Chinese innovative medicines are in a race to be listed in the United States —Who will become the first one?

5 Chinese innovative medicines are in a race to be listed in the United States —Who will become the first one?

The Chinese innovative medicine field is marching into a new phase. The number of novel drugs has exploded in the past few years and is riding on a steady upward trend. It is predicted that 15 to 20 new drugs will be approved from 2018 to 2020, at a speed of 4 to 5 per year at a minimum; the core focus of the industry is gradually shifting from generics to innovations. At the same time, the new emerging rank of Chinese biopharmas has increasingly set their sights on the international market, directly competing with global giants on developing medications against popular targets or aiming to become the first one to launch in a new class.

Among them, 5 drugs are most promising, either undergoing or planning their Phase III clinical trials in the United States. They are BGB-3111 from BeiGene, F-627 from E-Fan Pharmaceuticals, Ensartinib from Beta Pharma, Volitinib from Hutchison Medi Pharma, and Conbercept from Chengdu Kanghong Pharmaceutical Group. Who will become the first Chinese original innovative medication in the American market?  Let us wait and see!

BGB-3111

BGB-3111 is a highly selective BTK inhibitor developed by BeiGene.

The potential market of BTK inhibitors is huge. Currently, there is only one drug, Ibrutinib, on the market. It has received the FDA approval for the treatment of chronic lymphocytic leukemia in 2014. Worth mentioning is that its global sale has already reached $865 million in the 9 months before its official launch. With this dazzling result, Ibrutinib is on its way to becoming a blockbuster and its peak global sale is forecasted to reach a total of $8 billion.

Across the globe, BGB-3111 is another rising star, currently leading the research and development progress of BTK inhibitors. According to the results of its clinical trials, the effect of BGB-3111 is superior to Ibrutinib. However, its strongest competitor would be ACP-196, the fastest developing drug since Ibrutinib, equipped with the same robust clinical data. In the end of 2016, ACP-196 is already in phase III for CLL indications, potentially offering a new therapeutic option for patients who are resistant or not suitable for Ibrutinib. In December 2015, AstraZeneca invested $ 400,000 to acquire 55% of Acerta’s issued shares. This move is aimed to bag latter’s core product, ACP-196, which is expected to become the best in class product, with an annual sales peak of more than $5 billion.

In the face of ACP-196’s dazzling achievements, BeiGene has positioned its BGB-3111 to enter a different indication, in an effort to avoid directly competing with its strongest rival. In all global large-scale clinical trials, it is pitted against Ibrutinib and other leading runners of that disease. At present, ACP-196 has been greenlighted for one application; several others are under development. On the other side of the coin, BGB-3111 is being tested in 3 different diseases. According to BeiGene’s semi-annual report in 2016, BGB-3111 has obtained 3 orphan drug certifications from FDA, and is slated to showcase the progress of its combination drug clinical trial. Currently, its global Phase III clinical trials are ongoing and its Phase II clinical trials in China has started in December 2016.

From the current result in head-to-head trials with Ibrutinib, BGB-3111 is clearly superior to the former and significantly ahead of other Chinese BTK inhibitors. If the phase III clinical trials go well, it has a great potential to become a better in class product. And it is likely that BGB-3111 will be the first China-developed innovative medicine listed in the United States.

F-627

In 2016, E-Fan acquired 53.6% shares of an innovative drug research and development company DHY. This move has given them access to the latter’s advanced new drug discovery and production platform and a series of innovative large molecules in clinical and preclinical stages. Among them, the most promising one is F-627, currently undergoing phase III trials around the globe.

F-627 is classified as the third generation long-acting G-CSF. Compared to the first and the second generations, its bispecific structure puts it in the top spot to solve the severe neutropenia problem in tumor patients after chemotherapy. This has given it a clear leg up on its competitors, potentially setting F-627 as the most optimal recombinant human G-CSF drug.

On October 10th, 2017, FDA greenlighted F-627 to conduct its Phase III clinical trials following the guideline of the special protocol assessment (SPA). Under this program, the success rate of its listing increases dramatically. Currently, F-627 has started its Phase III clinical trials in 38 international centers across more than 20 countries around the world. In accordance with the US production reporting process, it is expected to be approved by the end of 2018 or the first quarter of 2019.

F-627’s direct competitor is Amgen’s Neulasta. When ensuring the same quality and efficacy, F-627 has some advantages in product measurement, dosing convenience, price, etc. The industry believes that as an innovative and long-acting G-CSF drug, F-627 is superior to of Hengri’s 19K both in technology and quality. Currently, Neulasta’s global sale is more than $4.6 billion, representing 70% of the total market. According to a third-party forecast, F-627 is expected to reach $1 billion globally.

Ensartinib

The third competitor is Ensartinib from Beta Pharma, an ALK inhibitor currently undergoing Phase III clinical trials in the United States. According to Haitong Securities, Ensartinib is slated to complete its China testing in 2018 and subsequently received its approval in 2019. Whereas in the United States, its listing date is later, scheduled to be around 2020 and 2021. People familiar with this matter predict that its peak sale will reach more than $300 million in China and around $43 million globally.

About a year ago, the entire market was worried about the disconnection of Beta Pharma’s R&D pipeline. However, with less than a year of effort to revive its business with collaborations and M&A, Beta has developed 6 innovative drug candidates ranging from Phase I to Phase III, including the ALK inhibitor Ensartinib.

According to the first-line data of ALK inhibitor treating non-small cell cancers, Ensartinib from Beta Pharma and Alectinib from Roche are most effective. Although Ensartinib is the 5/6 ALK inhibitor in the market nominally, from the therapeutic point of view, it is actually the third first-line ALK inhibitor. Its efficacy is superior to both Ceritinib from Novartis and Alectinib from Roche. Therefore, Ensartinib is expected to establish itself at the forefront of the competition and grab a total of 10%-15% of the market share.

In China, Ensartinib has adopted the second-line indication listing strategy, greatly speeding up its process to enter the market. After its approval in 2019, Ensartinib will become the only choice for Crizotinib resistant patients in China. Undoubtedly in the face of Crizotinib’s rising sale, Ensartinibi’s market share is expected to increase rapidly as well. By the end of 2020, Ensartinib is predicated to become the major player in the Chinese ALK inhibitor market.

Volitinib

Volitinib, co-developed by Hutchison Medi Pharma and AstraZeneca, is a selective c-Met inhibitor. In 2016, Hutchison has acquired 5% of Volitinib’s right outside China with $50 million, accounted for half of AstraZeneca’s raised funds in Nasdaq.

At present, there is no c-Met inhibitor which has successfully make its way into the market globally, largely thanks to its difficulties in selecting target populations and severe toxicities. Volitinib has the potential to become the world’s first high-selectivity c-met targeting medicine.

After years of clinical explorations, Volitinib has identified its possible target populations, including resistant non-small cell lung carcinoma patients following the EGFR-TKI therapy and patients with tumors driven by the c-Met gene. In July 2017, Hutchison Medi Pharma and Astra Zeneca have launched an international multi-center phase III trial for papillary renal cell carcinoma, which helped Hutchison receive a $5 million milestone payment from Astra Zeneca.

Worth mentioning is that the efficacy of Volitinib and Targrisso combo in non-small cell lung cancers is superior to the two drugs alone. In the wake of the large patient population with non-small cell lung cancers, undoubtedly, Volitinib will attract more revenues from the combined therapy.

Conbercept

In October 2016, the FDA approved ophthalmic Injection Conbercept to carry out Phase III clinical trials on age-related macular degeneration patients in the United States. This has sent shock waves across the spectrum of industry watchers, as it means Conbercept has exempted from Phase I and Phase II testings and goes straight into Phase III in the US market.

This is a very important milestone in Conbercept’s internationalization ambition. In October 2017, Kanghong threw $ 228 million to work with an American CRO company for its Phase III clinical trial, further demonstrated its determination to enter the international market. The current clinical trials are well under way.

Conbercept, listed in 2014, has filled the blank of Chinese Fundus macular degeneration drugs. After just two years into the market, its sales have reached a total of $70 million. However, according to people familiar with this matter, Conbercept currently accounts for less than 50% of the Chinese market share and has penetrated fewer than 1% of its target population, indicating that the figure can climb higher when the year goes on. What is more, Conbercept has entered the Chinese Medicare coverage through national drug pricing negotiations in July 2017. This undoubtedly will boost Conbercept’s revenue even further. It is expected that its sale will reach a total of $200 million in 2019.

In May 2017, Conbercept has got its hands on a new indication, pmCNV, adding another 2 million of target patient population. To make another step forward, Conbercept is also carrying out phase III clinical trials in both RVO and DME in China, expected to complete in 2018 and 2019 at the fastest respectively. By then, Conbercept’s total Chinese target population will exceed 10 million. In China, there are about 5 companies carrying AMD drugs in clinical trials. But they are at least 3-5 years away from making their ways into the market. Their influences would be minimal in the short term. At present, Conbercept’s direct competitor is Aflibercept, which has submitted an application for listing and has been included in the priority review. Aflibercept is expected to be approved in the first half of 2018. However, the general view of the industry is that Aflibercept will compete with Ranibizumba, instead of Conbercept.

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