FDA's Approval was Postponed Again, Chinese Innovative Pharmaceutical Companies has Extended Their Businesses to the Middle East and North Africa

The export of domestic PD-1 is much more difficult than expected. On December 23, Junshi Biosciences failed to get the FDA's reply letter on the Biologics License Application (BLA) of its PD-1 product - Toripalimab Injection as expected, which means that the FDA's relevant approval process was postponed again.

In March last year, Junshi Biosciences announced to submit the rolling marketing application to FDA about the Toripalimab for the treatment of recurrent or metastatic nasopharyngeal carcinoma, becoming the first domestic PD-1 antibody drug to submit the marketing application to FDA. In May, Junshi Biosciences announced to receive a complete reply letter from FDA about the BLA of the use of Toripalimab combined with gemcitabine/cisplatin as the first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma, and the use of the single-drug as the second-line or above treatment of recurrent or metastatic nasopharyngeal carcinoma after platinum-based treatment.

According to the letter, a change in the quality control process was needed before the official approval of Toripalimab. However, due to the travel restrictions related to COVID-19, the required on-site verification could not be completed in China as scheduled. Therefore, the review time of application for the marketing license of Tislelizumab would be extended until the on-site verification was completed.

In July 2022, TopAlliance announced that FDA had accepted the BLA application of Toripalimab and set the target review date of the Prescription Drug User Fee Act (PDUFA) as December 23, 2022. That is, the approval of the marketing application of Junshi Biosciences's PD-1 monoclonal antibody was determined before this date.

In fact, Toripalimab is the first anti-PD-1 monoclonal antibody approved for the treatment of nasopharyngeal carcinoma in the world. FDA has not approved to use any tumor immunotherapy for the treatment of nasopharyngeal carcinoma. Therefore, there are high hopes for the marketing of Junshi Biosciences's Toripalimab in the United States.

However, under the attention of the industry, the FDA postponed the approval again. On December 24, Junshi Biosciences announced that: they failed to get the FDA's reply letter on this BLA application of Toripalimab, which means that the expected result was not achieved on the original target review date, i.e. December 23. This is FDA's another postponement to the BLA application process for Toripalimab.

Because of the Difficulties in the United States, TopAlliance Turns to the Middle East and North Africa

According to the financial report of TopAlliance in 2021, the sales volume of Toripalimab was only RMB 412 million, which decreased by nearly 60% year-on-year, and was one of the worst performances among the domestic PD-1 disclosed. In the first three quarters of 2022, the sales volume of Toripalimab increased to RMB 516 million, but it was still at the bottom of the four main PD-1s. Because of the poor sales volume in China, the "Export" of TopAlliance is imperative.

This time, TopAlliance turns to the Middle East and North Africa. On December 25, Junshi Biosciences issued an announcement: it has signed the Exclusive License and Commercialization Agreement with Hikma, a company listed on the London Stock Exchange, which grants Hikma the exclusive license to develop and commercialize Toripalimab injection in 20 countries in the Middle East and North Africa, including Jordan, Saudi Arabia, the United Arab Emirates, Qatar, Morocco, Egypt, etc. In addition, it can get a total payment of up to US$ 12 million, plus a ladder sharing of nearly 20% of net sales.

Hikma was founded in 1978. After more than 40 years of development, now it has 31 pharmaceutical factories and 7 R&D centers in more than 50 countries in the world, with nearly 10,000 employees, and its products involve the drugs for anti-infection, cardiovascular disease, central nervous system disease, diabetes, tumor, pain management, respiratory system disease, etc. In 2005, Hikma was listed on the London Stock Exchange. Now Hikma employs more than 8,700 people, and has strong commercial experience in the drug market of the Middle East.

This year, the tightening of FDA's approval policies negatively affected the export of more than one domestic PD-1s. In February, the BLA application of Innovent's PD-1 inhibitor - Sintilimab - for non-squamous and non-small cell lung cancer (NSCLC) was rejected by FDA, with the reason that it needed to supplement clinical trials in the Americans before approval; The monotherapy of Tislelizumab, a PD-1 drug from BeiGene, for the indications of NSCLC was rejected by FDA due to the similar reason, because in clinical trials, it did not fully reflect the number of patients and the nursing standards used in the United States.

Since the big market in the United States is not feasible, domestic pharmaceutical companies began to make the shift in thinking. The Middle East and North Africa has become a new choice for the export of domestic innovative pharmaceutical companies in the past two years. It refers to the horizontal region from Morocco to Iran. This region connects three continents: Asia, Europe and Africa, two oceans: the Atlantic Ocean and the Indian Ocean, and five seas: the Caspian Sea, the Black Sea, the Mediterranean Sea, the Red Sea and the Arabian Sea. Locating in the place of "two oceans, three continents and five seas", it is an important strategic area. It is between the active East Asian economic circle and the developed European economic circle, with the huge economic development potential. Moreover, in terms of pharmaceutical regulation, most countries in the Middle East and North Africa have introduced the FDA-related systems to bring their regulatory standards in line with international standards, which have huge R&D advantages. In addition, the large population makes the Gulf countries in the Middle East a huge blue ocean market.

In addition to Junshi Biosciences, in June, Hangzhou Zhongmeihuadong Pharmaceutical Co., a subsidiary of Huadong Medicine, reached a cooperation with Julphar, a well-known enterprise in the Middle East to grant the rights and interests in the development, production and commercialization of its Liraglutide Injection for the two indications - diabetes and weight loss - in 17 countries in the Middle East and North Africa, including the United Arab Emirates, Saudi Arabia, Egypt, Kuwait and Oman, to Julphar.

In December, Tonghua Dongbao granted Kexing Biopharm the exclusive commercialized license rights of its Liraglutide Injection products in a total of 17 countries in Latin America, the Middle East, North Africa, Southeast Asia and South Africa.

Commercialization of Zanubrutinib, a BTK inhibitor of BeiGene, also includes the emerging markets and regions such as the Middle East and Africa.

At present, in addition to the US market, the Middle East and North Africa has become a new choice for the export of domestic innovative pharmaceutical companies. But innovation is the hard power of successful exports, regardless of destination. Compared with mature markets such as Europe and the United States, there are still a large number of unmet clinical needs in the Middle East and North Africa, which can not only be another choice for the export of domestic innovative pharmaceutical companies, but also provide new living space for them.

Main Reference Materials:

1. Announcement and financial report of TopAlliance;

2. https://www.biospace.com;

3. GLG Insight | Go into the Middle East and Africa: How can medical enterprises export steadily?, GLG, April 21, 2022

4. There is another way to the "Export" of innovative drugs: 51 pharmaceutical companies "Export" in the first half of 2022, Mu Haitang, July 28, 2022