Qilu Pharma Secures First Generic Approval for Tofacitinib Extended-Release Tablets as Global JAK Inhibitor Sales Hit $6.9 Billion; 17 Domestic Class 1 New Drugs in Pipeline

Recently, the field of JAK inhibitors has been experiencing a surge of activity: Qilu Pharmaceutical secured the first generic version of Tofacitinib Citrate Extended-Release Tablets, Pfizer's Abrocitinib Tablets were approved in China, and new indications were added for Tofacitinib Citrate Tablets… Currently, nine JAK inhibitors have been approved globally, five of which have received approval in China. The combined global sales of five JAK inhibitors in 2021 reached $6.89 billion, while the domestic market in China is still in its early stages. Among Chinese-produced JAK inhibitors, only the generic drug Tofacitinib Citrate Tablets has been approved so far, with 17 Class 1 new drugs under development by companies such as Hengrui, Kelun, and Zhengdatianqing.

Qilu Takes the Lead in Launching the First Generic Tofacitinib Sustained-Release Agent, Pfizer's Second JAK Inhibitor Arrives

Following the approval and launch of AbbVie's JAK inhibitor Upadacitinib Extended-Release Tablets in China, along with two new indications, another JAK inhibitor has entered the Chinese market. Meanwhile, Qilu Pharmaceutical's Tofacitinib Citrate Extended-Release Tablets, the first generic version, have closely followed.

On April 11, the National Medical Products Administration (NMPA) announced the approval and market launch of Pfizer's Class 1 innovative drug, the JAK1 inhibitor abrocitinib (brand name: CIBINQO), for adult patients with refractory, moderate to severe atopic dermatitis who have had an inadequate response to or are unsuitable for other systemic treatments (such as hormones or biologics). Abrocitinib is the second JAK inhibitor approved by Pfizer in China.

The first JAK inhibitor, Tofacitinib Citrate Tablets (brand name: Xeljanz), was approved for marketing in the United States in 2012 and imported into China in 2017. It is the world's first small-molecule targeted JAK kinase inhibitor for the treatment of rheumatoid arthritis. On April 18, Pfizer announced that the second indication for Tofacitinib Citrate Tablets had been approved and the first prescription in China was issued, for the treatment of ankylosing spondylitis.

In the Chinese market, Tofacitinib Citrate Tablets are caught in a fierce wave of generic substitution. Companies such as Bright Future Tianqing, Qilu Pharmaceutical, and Kelun Pharmaceuticals—15 enterprises in total—have received approval to produce generic versions of Tofacitinib Citrate Tablets. The oral conventional release formulation of Tofacitinib has also been included in the third batch of centralized procurement, further accelerating the substitution of the original drug.

On April 21, the official website of the National Medical Products Administration showed that Qilu Pharmaceutical's Tofacitinib Citrate Sustained-Release Tablets were approved for marketing, becoming the first generic version in China and the first to pass the evaluation. Qilu Pharmaceutical's Tofacitinib Citrate Tablets are the second domestically produced product, and the approval of this sustained-release formulation will further enhance the company’s competitiveness in the JAK inhibitor field.

Nine JAK Inhibitors Approved Globally, Five Major Products Combined for $6.9 Billion

JAK belongs to the non-receptor protein tyrosine kinase family, which consists of four subtypes: JAK1, JAK2, JAK3, and TYK2. As one of the popular R&D targets in the industry, there are already nine JAK inhibitors approved globally, involving pharmaceutical giants such as Pfizer, Eli Lilly, and Novartis.

Among the 9 JAK inhibitors, 5 are first-generation JAK inhibitors, including Novartis' ruxolitinib, Pfizer's tofacitinib, Eli Lilly's baricitinib, Astellas' peficitinib, and Japan Tobacco's delgocitinib; 4 are second-generation JAK inhibitors, including Celgene's fedratinib, AbbVie's upadacitinib, Gilead's filgotinib, and Pfizer's abrocitinib.

Data from MiNe Network shows that the global sales of five JAK inhibitors, including Ruxolitinib, Tofacitinib, Baricitinib, Upadacitinib, and Fedratinib, totaled $6.89 billion in 2021. Pfizer's Tofacitinib led with sales of $2.455 billion, while AbbVie’s Upadacitinib surpassed Novartis’ Tofacitinib in sales just three years after its launch.

Globally Marketed JAK Inhibitors

Currently, five JAK inhibitors—Tofacitinib, Ruxolitinib, Baricitinib, Upadacitinib, and Abrocitinib—have been successively approved for marketing in China. Due to their relatively late market entry, the domestic JAK inhibitor market is still in its infancy.

Data from Menet shows that the total sales of Tofacitinib, Ruxolitinib, and Baricitinib in Chinese urban public hospitals, county-level public hospitals, urban community health centers, and township health clinics (referred to as Chinese public medical institutions) were close to 400 million yuan in 2020, with combined sales exceeding 300 million yuan in the first half of 2021.

17 Class 1 New Drugs in Development! Hengrui, Kelun... Making Efforts

Although the JAK inhibitor market in China is still in its early stages, many local companies have already begun developing innovative drugs targeting the JAK pathway.

Currently, 17 novel Class 1 drugs targeting JAK inhibitors are in clinical research stages. Among them, SHR0302 from Hengrui Medicine and Jaktinib from Zelgen Biopharmaceuticals have entered Phase III clinical trials, representing the most advanced progress in development. Additionally, six other novel drugs are in Phase II clinical trials, including KL130008 capsules from Kelun Pharmaceuticals, TQ05105 tablets from Chia Tai Tianqing, and TLL-018 tablets from Disgene Medicine.

Research Status of JAK Inhibitors Produced in China

Hengrui Medicine's SHR0302 targets JAK1 and has developed two dosage forms: tablets and ointments, with multiple indications in its pipeline. Currently, the indications for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, atopic dermatitis, alopecia areata, and colitis of SHR0302 tablets have all entered Phase III clinical trials, and the indication for atopic dermatitis has been included in the breakthrough therapy program.

Zelgen's Jaktinib is a JAK inhibitor-targeted small molecule, developed in two dosage forms: tablets and cream. Currently, the myelofibrosis and severe alopecia areata indications for Jaktinib Hydrochloride Tablets are both in Phase III clinical trials; the mild-to-moderate alopecia areata and mild-to-moderate atopic dermatitis indications for Jaktinib Hydrochloride Cream are both in Phase I clinical trials.

KL130008 capsule, developed by Sichuan Kelun BoTai, a holding subsidiary of Kelun Pharmaceutical, is a selective inhibitor targeting JAK1 and JAK2 kinases. The product is currently in Phase II clinical trials for the indication of rheumatoid arthritis, and its indication for severe alopecia areata was approved to enter Phase II clinical trials in March 2022. TQ05105 tablets from Zhengda Tianqing are JAK and ROCK inhibitors, and their indication for myelofibrosis is currently in Phase II clinical trials.

In terms of R&D progress, Hengrui Medicine's SHR0302 is expected to become the first domestically produced innovative JAK inhibitor in China.

Data source: MiNeiNet database, NMPA, etc.

Note: Data statistics are as of April 21. If there are any omissions, corrections are welcome!