17 First-in-Class Generic Drugs Approved for Production, with Hengrui and Kelun Leading the Race with Three Each

PharmNet, September 5 — First-to-file generic products have consistently been a key focus in the R&D strategies of Chinese pharmaceutical companies. With the reform of China’s new drug review and approval system, particularly the formal implementation of the priority review pathway, the approval timeline for first-to-file generics has been accelerating. According to statistics from Menet, 17 first-to-file generic products have received production approval since 2018 (five of these products achieved sales exceeding RMB 500 million in China’s public healthcare institutions in 2017). Among them, five products were submitted under the new Class 3/4 regulatory category and are deemed to have passed the consistency evaluation upon market approval. Hengrui Medicine and Kelun Pharmaceutical lead with three first-to-file generic products each.

 

　　Table 1: First Generic Products Approved for Market Launch from 2018 to Present

 

Note: Currently, there is no official document that defines the concept of "first generic." The statistical basis for this article comes from the 2012 Guangdong Provincial Price Bureau's issuance regardingPharmaceuticals“First-to-File Generic Concept” Proposed in the Notice on Administrative Measures for Differential Pricing

　　

(Source: Menet Database, data statistics as of September 4)

 

 

Among the 17 first-to-market generic products, four were submitted for marketing approval under New Drug Application Category 4: Solifenacin Succinate Tablets (Sichuan Guowei Pharmaceutical), Ambrisentan Tablets (Jiangsu Hansoh Pharmaceutical), Ticagrelor Tablets (Shenzhen Salubris Pharmaceuticals), and Paclitaxel for Injection (Albumin-bound) (CSPC Ouyi Pharmaceutical). One product was submitted for production approval under New Drug Application Category 3: Ibuprofen Injection (Chengdu Yuandong Bio-pharmaceutical). Upon approval, these five products are deemed to have passed the consistency evaluation and are eligible for policy incentives.

 

Ticagrelor is a direct-acting, reversibly binding P2Y12 platelet inhibitor that effectively reduces the incidence of thrombotic cardiovascular events. Ticagrelor (brand name Brilinta), developed by AstraZeneca, received approval from the U.S. FDA for market launch in July 2011. Since its introduction, Brilinta’s sales have risen year by year, reaching $1,079 million globally in 2017 and becoming a global blockbuster drug.

 

Figure 1: Sales of Ticagrelor Tablets at Public Medical Institution Terminals in China, 2013–2017 (Unit: 10,000 Yuan)

(Source: Menet’s Competitive Landscape of China’s Public Medical Institution Terminal)

 

In December 2012, AstraZeneca’s ticagrelor (brand name Brilinta) entered the Chinese market and has since been included in the 2017 National Reimbursement Drug List, with its price reduced by 22.78%. According to data from Menet, sales of ticagrelor tablets at public medical institutions in China reached RMB 503 million in 2017, representing a year-on-year increase of 42.15%. Currently, AstraZeneca, as the originator manufacturer, holds a dominant position in the domestic market. The launch of Shenzhen Salubris’ generic version of ticagrelor tablets, being the first generic approval, is expected to continuously drive the expansion of the ticagrelor market amid strong essential demand.

 

Paclitaxel for Injection (Albumin-Bound) is a novel formulation of paclitaxel bound to albumin, developed by Abraxis BioScience for the treatment of cancers such as breast cancer. Marketed under the brand name Abraxane, it was approved by the FDA in January 2005 for the indication of breast cancer, with subsequent approvals for indications including lung cancer and pancreatic cancer. In 2010, Celgene acquired Abraxis, thereby adding Abraxane to its portfolio.

 

Figure 2: Sales of Albumin-Bound Paclitaxel for Injection at Public Medical Institution Terminals in China, 2013–2017 (Unit: 10,000 Yuan)

(Source: Competitive Landscape of China's Public Medical Institutions Terminal, Menet)

 

In 2008, Abraxis’ albumin-bound paclitaxel for injection entered the Chinese market. According to data from Menet, the overall market for paclitaxel at public medical institutions in China reached RMB 5.724 billion in 2017, representing a year-on-year increase of 13.46%. Among the top 20 paclitaxel brands, albumin-bound paclitaxel for injection ranked third with sales of RMB 516 million and a market share of 9.02%.

 

Currently, in the domestic market, apart from the original manufacturer Celgene, CSPC Pharmaceutical Group is the earliest to have received approval for production and passed the consistency evaluation of paclitaxel injection (albumin-bound). HengruiPharmaceuticalsPaclitaxel for Injection (Albumin-bound) has completed review and is in the "on-site production inspection" stage. According to the latest update, this product has been approved for production by the National Medical Products Administration. In addition, the bioequivalence (BE) trial of this product registered in ChinaEnterpriseOther companies include Hunan Kelun, Chia Tai Tianqing, and Qilu Pharmaceutical. Among them, Qilu Pharmaceutical has submitted a marketing application and may become the third company to launch this product in China.

 

Ambrisentan tablets are a selective endothelin receptor antagonist used to treat pulmonary arterial hypertension. On June 15, 2007, ambrisentan tablets (brand name Volibris), jointly developed by Gilead Sciences and GlaxoSmithKline, received approval from the U.S. FDA for market launch. Based on Gilead’s sales performance in recent years, the sales revenue of ambrisentan tablets has increased year by year since its launch, reaching $887 million globally in 2017, representing an 8.3% year-on-year growth.

 

According to data from Menet, as of now, in addition to Jiangsu Hansoh Pharmaceutical, which has already received approval for production, companies such as Chia Tai Tianqing Pharmaceutical Group, Zhejiang Huahai Pharmaceutical, and Jiangsu Deyuan Pharmaceutical have submitted Class 4 manufacturing applications for ambrisentan tablets, which are currently “under review and approval.” Furthermore, companies including Jiangsu Jiayi Pharmaceutical, Wuhan Humanwell Pharmaceutical, and Tianjin Chase Sun Pharmaceutical have registered bioequivalence (BE) trials for this product.

 

Ibuprofen Injection belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs) and possesses antipyretic, analgesic, and anti-inflammatory properties. The manufacturing application for Ibuprofen Injection produced by Chengdu Yuandong Bio-pharmaceutical entered the on-site production inspection stage in 2015, but due to coinciding with 2016Drug RegistrationIn the stormy year of review and approval reforms, with strict scrutiny of clinical data, Chengdu Yuandong Bio-Pharmaceutical’s production application was announced as withdrawn in January 2016. In August 2016, the company re-applied for market launch under Class 3 in accordance with the new registration management measures, with the claim of “consistent quality and efficacy with the original drug”StandardGranted priority review status under the rationale of “the first product variety to be re-submitted after improvement,” it received production approval in August 2018. To date, Jilin Sihuan Pharmaceutical and Hangzhou Minsheng Pharmaceutical have submitted production applications for this product, which remain “under review and approval.”

 

 

“King of R&D” Hengrui Medicine has achieved remarkable success in the field of innovative drugs and also leads the way in the generic drug sector. Since 2018, Hengrui Medicine has had three first-to-file generic products approved for marketing, namely desflurane for inhalation, fondaparinux sodium injection, and paricalcitol injection.

 

Inhaled desflurane is indicated for the induction and/or maintenance of anesthesia in adult inpatients and outpatients, as well as for the maintenance of anesthesia in infants and children. Desflurane (brand name Suprane), originally developed by Baxter USA, received FDA approval for marketing in 1992 and is currently available in multiple countries and regions, including China, the European Union, Japan, and South Korea. According to data from Menet, sales of inhaled desflurane at public medical institutions in China approached RMB 100 million in 2017. Apart from the original manufacturer Baxter and Hengrui Medicine, no other companies have currently submitted production applications for this product.

 

Fondaparinux Sodium Injection helps prevent venous thromboembolic events. It was developed by the US company MYLAN IRELAND LTD. and approved by the FDA for marketing on December 7, 2001. In 2009, ARIXTRA (Arixtra) from the UK company Glaxo Group Ltd was approved for marketing in China, and in 2015 it was changed to ARIXTRA (Arixtra) from Aspen Notre Dame de Bondeville in Ireland. In addition to the original manufacturer and Hengrui Medicine, other companies such as Chia Tai Tianqing, Tianjin Hongri, Xintai Pharmaceutical, and Liaoning Haishike have submitted Class 6 applications in the domestic market, but no company has yet been approved for production.

 

Paricalcitol Injection, a new-generation selective vitamin D receptor agonist (VDRA), is indicated for the treatment of secondary hyperparathyroidism in patients with chronic renal failure undergoing hemodialysis. In the domestic market, apart from the originator and Hengrui Medicine, there are currently approximately five companies with this product under development or pending approval.

 

 

“The IV Infusion Leader” Kelun Pharmaceutical has comprehensively constructed a product strategy layout of “promoting innovation through generics, and driving the future with innovation.” Leveraging its advantages in generic drug experience, it continuously launches first-to-market generic and exclusive parenteral nutrition products, maintaining its leading position in the formulation sector. From 2018 to present, Kelun Pharmaceutical has received approval for three first-to-market generic products: Fat Emulsion Amino Acid (17) Glucose (19%) Injection, Fat Emulsion (10%)/Amino Acid (15)/Glucose (20%) Injection, and Amino Acid Glucose Injection.

 

Fat Emulsion, Amino Acids (17), and Glucose (19%) Injection is a three-chamber bag for parenteral nutrition, indicated for adult patients who are unable, have insufficient function, or are contraindicated to receive nutrition orally/enterally. It is listed as a Class B drug under the National Medical Insurance Scheme. The originator company is Fresenius Kabi. It was first launched in Germany in 1999 under the brand name Kabiven, and received import approval in China in 2004 under the brand name Kaquan.

 

Fat Emulsion (10%)/Amino Acids (15)/Glucose (20%) Injection is the world’s first industrially manufactured “all-in-one” three-chamber bag product, indicated for nutritional support in children aged 2 years and older and adult patients who are unable, have insufficient function, or are contraindicated for oral/enteral nutrient intake. The original manufacturer is Baxter, and it was first approved for marketing in France in 1997, making it the earliest three-chamber bag product launched globally. It received approval from the National Medical Products Administration for marketing in China in 2013, under the brand name Clinimix.

 

Figure 3: Sales of Fat Emulsion, Amino Acid, and Glucose Injection at Public Medical Institution Terminals in China, 2013–2017 (Unit: 10,000 Yuan)

(Source: Menet Network – Competitive Landscape of China’s Public Medical Institutions Terminal)

 

According to data from Menet, in 2017, the sales revenue of fat emulsion, amino acid, and glucose injection at public medical institutions in China reached RMB 1.592 billion, a year-on-year increase of 12.72%. Among them, the sales revenue of fat emulsion amino acid (17) glucose (19%) injection was RMB 1.443 billion, accounting for 90.65% of the market share; the sales revenue of fat emulsion (10%)/amino acid (15)/glucose (20%) injection was RMB 99 million, accounting for 6.19% of the market share.

 

Amino Acid and Glucose Injection is the first amino acid-glucose ready-to-use parenteral nutrition dual-chamber bag marketed in China, and it is the only series of dual-chamber bags available globally that can be used in pediatric patients. The original manufacturer is Baxter, which first launched the product in France, Spain, and other countries in 1996. It is currently marketed in more than 10 countries, including the United Kingdom, Italy, and the Netherlands. Kelun Pharmaceutical is the first enterprise in China to obtain production approval for amino acid and glucose injection; to date, no other enterprises have submitted applications for the production of this product.

 

　　Source: Menet Database, Announcements of Listed Companies