Gilead Leads Multinational Pharma Innovation in China with Aggressive Hepatitis and HIV Drug Launches

Pharmaceutical Network, April 15 — In 2018, multinational pharmaceutical companies launched a total of 44 new drugs in China, accounting for 77% of all approved new drugs. Among them, Gilead Sciences demonstrated the strongest momentum in new drug launches, Boehringer Ingelheim had the highest number of launches, Sanofi showed a particular preference for rare disease treatments, while Pfizer, the “global pharmaceutical giant,” was the most disappointed, having launched only two new drugs in China over the past two years.

 

Recently, IDEA Pharma released its 9th pharmaceuticalEnterpriseAnnual Innovation Index (PII), in which Gilead Sciences topped the industry innovation rankings for the first time, followed by AbbVie, Eli Lilly, Pfizer, Merck Sharp & Dohme, Sanofi, Novo Nordisk, Roche, Novartis, and GlaxoSmithKline. This ranking reflects pharmaceutical companies’ ability to advance products from Phase 1 and Phase 2 clinical trials to market launch and successfully achieve commercialization.

 

In China, with the continuous reform of new drug review and approval processes and clinical trial reforms, the research, market access, and commercialization capabilities of innovative drugs from multinational pharmaceutical companies have increasingly become important competitive factors in the Chinese market. Especially the "4+7 volume-basedProcurement” This further validates the strategy that the era of high growth for multinational pharmaceutical companies’ original drugs facing patent expiration will come to an end. In the future, multinational pharmaceutical companies will also compete in China based on innovative drugs!

 

In 2018, a total of 57 new drugs were approved for marketing in the Chinese market, a figure approaching the record-breaking 59 new drugs approved by the US FDA, reflecting that the review and approval efficiency of the National Medical Products Administration (NMPA) was on par with its US counterpart. Among these, there were 33 imported chemical drugs and 11 imported biological drugs. Multinational pharmaceutical companies launched a total of 44 new drugs in China, accounting for 77% of all newly approved drugs. The continuous increase in the number of approvals also indirectly reflects the considerable efforts made by multinational corporations to expand their respective product portfolios.

 

 

Among them, the top five pharmaceutical companies with the most new drugs launched in China in 2018 were Gilead Sciences, Merck Sharp & Dohme, Boehringer Ingelheim, Sanofi, and Roche. This ranking differs slightly from that of 2017: in 2017, the top five pharmaceutical companies with the most new drugs launched in China were Boehringer Ingelheim, Novartis, AstraZeneca, Johnson & Johnson, and AbbVie/Bristol-Myers Squibb/Bayer.

 

How robust are the innovative drug portfolios of these multinational pharmaceutical giants in China? Which company has launched the most products? Which has achieved the fastest sales ramp-up? And which has employed the most unexpected strategies?

 

 

In 2018, Gilead Sciences launched five new drugs in the Chinese market. With the addition of one drug from 2017, a total of six innovative medicines were approved for launch within 15 months, making it the biggest winner among multinational pharmaceutical companies in terms of new drug approvals in China in 2018.

 

This U.S. company, which fully entered the Chinese market in 2016, has clearly made new drugs a key focus of its growth strategy in China. The five innovative drugs approved in 2018 are all rooted in the hepatitis and HIV/AIDS markets, achieving multiple “firsts” in China.

 

In May 2018, following the launch of its blockbuster hepatitis C drug Sovaldi in China, Gilead Sciences secured approval in China for another major new drug, Epclusa (sofosbuvir/velpatasvir), for the treatment of adult patients with chronic hepatitis C virus (HCV) infection genotypes 1–6. This marked the first pan-genotypic single-tablet regimen (STR) for HCV approved in China.

 

Five months after its approval, Epclusa was included in the National Essential Medicines List (2018 Edition) in October of that year and is highly likely to be incorporated into the National Reimbursement Drug List in the upcoming round of adjustments.

 

In August 2018, Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide tablets) was approved in China for the treatment of HIV-1 infection, becoming the first single-tablet regimen containing TAF/FTC approved in the country for treating HIV infection in adults and adolescents. Compared with multi-pill regimens, the “all-in-one,” “one pill once daily” approach can better improve patient adherence. Globally, Genvoya generated over $3.6 billion in sales for Gilead Sciences in 2017, representing a 148% increase from $1.484 billion in 2016.

 

In November 2018, Gilead Sciences had three new drugs successively approved in China: Vemlidy for the treatment of chronic hepatitis B, Descovy for the treatment of HIV-1 infection, and Sofosbuvir/Velpatasvir for the treatment of genotype 1–6 chronic hepatitis C.

 

Vemlidy is the first new oral medication approved in the Chinese market for the treatment of hepatitis B in a decade, and upon approval, it was hailed as the “most potent” new drug for hepatitis B in history. Vemlidy exhibits antiviral efficacy similar to that of Gilead’s tenofovir disoproxil fumarate (TDF), but at only one-tenth of the latter’s dosage.

 

 

Boehringer Ingelheim (BI) has launched the highest number of innovative drugs among multinational pharmaceutical companies in China over the past two years, achieving remarkable success. Specifically, it launched five innovative chemical drugs in 2017, and in 2018, it introduced one innovative small-molecule chemical drug and two innovative biologics.

 

Among them, olodaterol aerosol and tiotropium/olodaterol inhalation spray represent the latest generation of therapies, having been marketed abroad for over three years with robust clinical evidence. The launch of these two new drugs has significantly expanded the clinical treatment options for COPD and is expected to alter the current market landscape dominated by a single player in the treatment of asthma and COPD.

 

In 2017, Boehringer Ingelheim saw the successive approval and market launch of telmisartan/amlodipine (Twynsta) for hypertension; empagliflozin (Jardiance) and linagliptin/metformin (Jentadueto) for type 2 diabetes; nintedanib (Ofev) for idiopathic pulmonary fibrosis; and afatinib (Giotrif) for non-small cell lung cancer. These approvals not only significantly enriched its innovative drug pipeline but also expanded Boehringer Ingelheim’s presence in China into a broader range of therapeutic areas, including cardiovascular disease, metabolism, oncology, respiratory diseases, central nervous system disorders, and immunology.

 

 

Compared with other multinational pharmaceutical companies, Pfizer, the “global big pharma,” has been slightly disappointing in launching innovative drugs in China in the past two years. Recently, at the 4th Chinese Medical Affairs Conference (CMAC) held in Shanghai, Gu Chengming, Chief Medical Officer of Pfizer China, publicly joked, “We haven’t faced much pressure in the past two years because we haven’t launched any new drugs in China.”

 

Although the number is small, Pfizer has actually had one new drug approved each year in China over the past two years. In 2017, the marketing application for tofacitinib, an oral JAK inhibitor for the treatment of rheumatoid arthritis, was submitted in China; in 2018, palbociclib capsules (Ibrance) for the treatment of breast cancer were approved.

 

It is worth noting that tofacitinib, approved in 2017, was the first JAK inhibitor approved for the treatment of patients with rheumatoid arthritis and has been approved in more than 50 countries worldwide. Palbociclib, approved in China in July 2018, is the world’s first selective inhibitor of cyclin-dependent kinases (CDK) 4/6. In 2013, the U.S. Food and DrugPharmaceuticalsThe U.S. Food and Drug Administration (FDA) approved Ibrance as a breakthrough therapy for advanced breast cancer. In 2015, the FDA granted accelerated approval for Ibrance for the treatment of advanced breast cancer. Based on this, the National Comprehensive Cancer Network (NCCN) Guidelines recommend Ibrance in combination with an aromatase inhibitor as a first-line treatment regimen for HR+/HER2- advanced or metastatic breast cancer.

 

In the global market, Ibrance’s sales exceeded $2 billion in its second year on the market, reaching $3.5 billion in 2017, with a growth rate of over 117%. However, its current pricing in China is relatively high, at RMB 29,800 per box. With seven boxes required for a six-month course of treatment, the total cost amounts to RMB 208,600.

 

However, the favorable market conditions for this blockbuster new drug in China were short-lived. In November 2018, CPM data showed that the generic drug application for palbociclib capsules submitted by Qilu Pharmaceutical had changed to “accepted” status. In addition, 13 other companies, including Hansoh, Hengrui, Hisun, and Chia Tai Tianqing, were conducting clinical trials on palbociclib capsules. Although Ibrance is still under patent protection, it is foreseeable that the product will soon face intense competition. Pfizer will also come under significant pressure.

 

On November 21, 2018, Pfizer’s palbociclib capsules were included in the Shenzhen Supplemental Medical Insurance Catalogue for Critical and Severe Diseases. Under pressure from generic competitors, Pfizer may seek to lower prices or gain inclusion in the national medical insurance scheme to secure market share ahead of schedule.

 

 

Sanofi launched three new drugs in China in 2018, a slight increase from the one new drug launched in 2017. Two of these three new drugs are for rare diseases.

 

China is gradually increasing its attention to the field of rare disease treatment. In May 2018, five ministries jointly announced the "First Batch of Rare Diseases Catalog," providing strong policy support for the diagnosis and treatment of rare diseases. On March 28, 2019, the CDE released the second batch of clinically urgent overseas new drugs list, which included 14 rare disease drugs.

 

In July 2018, Sanofi’s teriflunomide tablets (Aubagio) were approved in China for the treatment of relapsing forms of multiple sclerosis (MS), marking the first oral disease-modifying therapy (DMT) for multiple sclerosis approved in the country. Multiple sclerosis has been included in China’s “First Batch of Rare Diseases Catalog.” From approval to market availability, Aubagio took only 58 days, setting a recent record for the fastest transition from approval to launch for an innovative rare disease drug in China.

 

In December 2018, Sanofi Genzyme’s rare disease therapy Mozobil (plerixafor injection) was approved in China. As a next-generation hematopoietic stem cell mobilization agent, Mozobil can significantly improve the success rate of hematopoietic stem cell collection, providing patients with more opportunities for cure through transplantation.

 

Since acquiring Genzyme, the US giant in rare diseases, Sanofi has developed a strong focus on rare diseases, deepening its footprint in hemophilia and other rare disease areas. Globally, Sanofi acquired the Belgian pharmaceutical company Ablynx in 2018; Ablynx’s flagship new drug targets rare blood coagulation disorders. In early 2018, Sanofi acquired Bioverativ for $11.6 billion. This company specializes in hemophilia. These two acquisitions cost Sanofi a total of $16.4 billion.

 

Recently, Shanxi Province also confirmed the inclusion of two rare disease drugs under Sanofi—Cerezyme, a specific drug for treating Gaucher disease, and Myozyme, a specific drug for treating Pompe disease—into the scope of medications covered by critical illness insurance, and determined the medical insurance payment standards.StandardsSubsequently, policies will provide corresponding support for rare disease drugs in areas such as review, market access, medical insurance, and pricing. Rare diseases in China may also become a cradle for nurturing “blockbuster” drugs.

 

Recently, Olivier Bogillot, Executive Vice President and Global Head of General Medicines and Emerging Markets at Sanofi, revealed in an interview that rare diseases will become a key component of Sanofi’s strategy in China. To this end, Sanofi will establish a new business unit in China and other emerging markets.

 

05. MSD: PD-1 Makes Debut in China, Nine-Valent HPV Vaccine Approved in 8 Days

 

In 2018, the Chinese market was particularly important for Merck Sharp & Dohme (MSD). That year, MSD obtained approval for five innovative drugs in China, including the blockbuster PD-1 inhibitor Keytruda and the nine-valent HPV vaccine, which was approved within just eight days. In the second quarter of 2018, MSD achieved a 26% year-on-year growth, with the Asia-Pacific region recognized as one of the strongest growth drivers.

 

Just weeks after the approval of Bristol Myers Squibb’s (BMS) PD-1 inhibitor Opdivo, Merck Sharp & Dohme’s (MSD) PD-1 inhibitor Keytruda was approved in China in July 2018 for the treatment of melanoma. Keytruda generated global sales of $7.171 billion in 2018 and also demonstrated robust growth in the Chinese market, with reported sales exceeding RMB 500 million within just four months. In early April 2019, Keytruda was officially approved in China for first-line treatment of non-small cell lung cancer (NSCLC) in combination with chemotherapy. Globally, more than 60% of Keytruda’s revenue comes from its lung cancer indications, suggesting that the drug will continue to experience rapid growth in the Chinese market.

 

Following the approval of the nine-valent HPV vaccine in China, demand surged explosively. Its exclusiveAgentIn November 2018, Zhifei Biological Products issued an announcement stating that future procurement amounts for HPV vaccines would increase significantly, with procurement values of RMB 5.507 billion in 2019, RMB 8.33 billion in 2020, and RMB 4.165 billion in 2021. These figures represent 7.4 times, 11.2 times, and 5.6 times the procurement volume of 2017, respectively. The strong demand for HPV vaccines has driven a substantial rise in Merck Sharp & Dohme’s performance. According to MSD’s semi-annual report for the Chinese market, its sales in China exceeded RMB 6.557 billion in the first half of this year, marking a year-on-year increase of 33.15% compared to RMB 4.924 billion in the same period last year.

 

 

In 2018, Roche launched three new drugs in China, including the new chemical drug alectinib and two innovative biologics: pertuzumab and emicizumab.

 

In August 2018, alectinib (Alecensa) was approved in China for the treatment of ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), and it is currently the best-in-class ALK inhibitor. On December 11, 2015, alectinib received its initial FDA approval for marketing. On November 6, 2017, the FDA further approved alectinib as a first-line therapy for patients with ALK-positive NSCLC, thereby achieving essentially simultaneous market launch in China and the United States. Globally, alectinib has demonstrated strong momentum in expanding its market share, with sales reaching CHF 362 million (+101%) in 2017 and USD 279 million (+91%) in the first half of 2018.

 

In December 2018, Roche’s innovative targeted therapy Perjeta (pertuzumab) was approved in China for adjuvant treatment in combination with trastuzumab and chemotherapy in patients with HER2-positive early breast cancer at high risk of recurrence. Pertuzumab, developed by Roche’s subsidiary Genentech, was first approved in 2012. The dual-targeted regimen combining pertuzumab with Herceptin has been recommended in multiple clinical guidelines and consensus statements worldwide and has received regulatory approval in more than 75 countries. Perjeta has also been included in national reimbursement lists in 44 countries or regions globally.

 

Emicizumab is an innovative drug included in the priority review program as a treatment for rare diseases and a clinically urgent need. Developed by Chugai Pharmaceutical, a subsidiary of Roche, it is indicated for routine prophylactic treatment in patients with hemophilia A with congenital factor VIII deficiency.

 

Four targeted drugs under Roche—trastuzumab, rituximab, bevacizumab, and erlotinib—were included in the National Reimbursement Drug List (NRDL) through price negotiations in 2017, with price reductions of 50%–70%. Within two months, reimbursement policies were rapidly implemented across various regions. According to E-Pharma Manager, Roche China’s sales volume surged by 75% in 2018, while sales revenue increased by 28%. Zhou Hong, head of Roche China, recently stated in an interview with E-Pharma Manager that the company aims to have all three new drugs approved in 2018 included in the NRDL in 2019.