Under the "double shackles" of capital and international supervision, where is the "Kangzhuang Avenue" of "going to sea" pharmaceutical companies?

After the revelry, it is finally calm

"Throttling"

For example, Genting Xinyao's "meat cutting" core product TROP-2 ADC goshatozumab is "bloody and life-saving"; Watson Bio terminated clinical research on recombinant EV71 vaccine due to the predictable low social and economic benefits of the product; Clover suspended its investment in three clinical pipelines and prioritized resources for COVID-19-related products and early-stage projects

Under the difficult times, some enterprises that choose "open source hematopoiesis" to judge the situation and size up the situation have obtained gratifying benefits, in order to make full "backing" for the research and development of innovative projects and the expansion of the international market:

"Open Source Hematopoiesis"

For example, Henlius has entered into License-out deals with a number of multinational companies, and the transaction with Organon for HLX11 and HLX14 will bring potential revenue

In addition to solving its own product pipeline and funding problems, BIOTECHS is also facing an increasingly "harsh" international regulatory environment

International supervision has become stricter, and "folding" incidents have occurred frequently

International supervision has become stricter, and "folding" incidents have occurred frequently

According to a recent special report released by GBI (click to read relevantly), in the first half of 2022, in terms of the distribution of product therapies of Chinese companies License-out, biological drugs including monoclonal antibodies, ADCs, other antibodies and cell therapies accounted for 69%

GBI (click to read)

Although domestic innovative drugs are increasingly recognized by overseas companies and have increasing influence in the world, it is not difficult to see from the recent FDA approval trend of new drugs in the United States and the frequent cases of "going to sea" that international supervision is becoming stricter, and differentiated innovation that can meet local unmet clinical needs is the key

International supervision is becoming stricter, and differentiated innovation that can meet the local unmet clinical needs is the key

Table 1.

Table 1.

Source: GBI SOURCE Global Drug Database

GBI SOURCE Global Drug Database

The tightening of supervision can also be glimpsed from the twists and turns of the domestic PD-1's "going to sea"

The tightening of supervision can also be glimpsed from the twists and turns of the domestic PD-1's "going to sea"

Refusal to list Daboshu;

In May 2022, the review date of Junshi Biotuoyi (Treplelimab) was delayed

COVID-19-related travel restrictions

In July 2022, BeiGene announced that the US FDA was unable to complete the required on-site verification work in China as scheduled due to COVID-19-related travel restrictions, and would extend the review time of The BLA for second-line treatment of patients with unresectable or metastatic esophageal squamous cell carcinoma by The US FDA, and the date of the new PDUFA has not been determined

COVID-19-related travel restrictions

International Multi-Center Clinical: The "Hurdle" That Can't Be Bypassed

International Multi-Center Clinical: The "Hurdle" That Can't Be Bypassed

Concerned about the reasons for the setback of the domestic PD-1 "going to sea", Junshi and Baekje have been temporarily hindered by the new crown epidemic, while Cinda Daboshu has been explicitly rejected due to the lack of international multicenter clinical trial (MRCT) data that can represent Patients in the United States

International multicenter clinical trials (MRCT) data that represent patients in the United States are lacking

It is worth noting that the FDA has given negative feedback due to the lack of clinical trial data representing the U.

In March 2021, Athenex's oral paclitaxel formulation Oraxol was not approved for marketing

"Represents the population of the United States"

In May 2022, Hehuang Pharmaceutical announced that the US FDA has delayed the listing application of sofotinib for the treatment of pancreatic and non-pancreatic neuroendocrine tumors
.
The FDA noted that the data packages from the Sulfantinib China Phase III study and a US bridging study were not sufficient to support approval in the US and that more MRCT
representing PATIENTS in the US needed to be included.

More MRCT representing patients in the United States need to be included
.

The frequent occurrence of "folding" incidents is sending a signal to the "latecomers" that differentiated and innovative products are prerequisites, and that MRCTts that represent local demographic characteristics may be more conducive to approval
.
This is why the industry is still positive about the results of the review of Junshi and Baekje PD-1 products
.
Since no tumor immunotherapy has been approved for nasopharyngeal cancer treatment in the United States, the treatment of NASOPRIN in the treatment of nasopharyngeal carcinoma meets the "unmet clinical needs"
.
The indications for baekje tirrizumab for the second-line treatment of esophageal squamous cell carcinoma are based on MRCT in the true sense, and the test results also show the advantage of overall survival, so compared with other domestic "going to sea" PD-1, the clinical data of tirelizumab may be more convincing and conducive to its approval
.
BeiGene can be described as a representative of "independent going to sea", the company has a R & D team of more than 2900 people, including 2200 global clinical development team, strong independent clinical development capabilities make it basically achieve "decrocro"
.
BeiGene conducts clinical trials in multiple countries and territories around the world to recruit patients faster and reduce the time and cost of clinical trials by one-third
.

Differentiated and innovative products are prerequisites, and AN MRCT that represents the local demographic characteristics may be more conducive to approval
.
MRCT in the true sense of the word

Agile access, the United States is not the only solution

Agile access, the United States is not the only solution

In fact, for the domestic leading innovative pharmaceutical companies that pursue real innovation and are committed to long-term expansion of overseas "territory", international research and development is ultimately a "barrier" that is difficult to avoid, and with the tightening of supervision, the necessity and first-mover advantage of the global clinical trial layout based on "access to increase the size of the forced research and development" have become increasingly prominent
.
In addition to baekje-like "bellwethers", other companies aiming for overseas markets are also making great strides
.
According to GBI incomplete statistics, at present, there are nearly 60-70 local biotechnology companies in China that have actively laid out medium- and long-term clinical research and development in the international market, including Cinda Biologics, Kangfang Biologics, Nuocheng Jianhua, Pioneering Pharmaceuticals, Fuhong Henlin, etc
.

The necessity and first-mover advantage of the global clinical trial layout based on "access to increase the size of the forced research and development" have become increasingly prominent
.
GBI

Table 2.
Some local biotechnology companies have a layout of drugs for multi-country clinical trials

Table 2.
Some local biotechnology companies have a layout of drugs for multi-country clinical trials

Source: GBI SOURCE Global Drug Database

GBI SOURCE Global Drug Database

It is worth noting that in addition to the United States, the international clinical layout of pharmaceutical companies is touching many European countries and other emerging markets
.
From the previous GBI global access projects, we also found that although the United States is the "most ideal" access market, for most pharmaceutical companies, after comprehensive consideration of disease spectrum, registration supervision, competitive landscape, substandard clinical needs, patient groups, tax environment, etc.
combined with the characteristics of the products, they often take the lead in successfully entering countries
outside the United States.
Facts have proved that the United States is not the "only solution to victory", the opportunities and potentials contained in emerging markets should not be underestimated, and the "curve to save the country" market access strategy is also a good strategy
for successfully "going to sea".

The GBI global access project in the United States is not the "only solution to win", the opportunities and potential contained in emerging markets should not be underestimated, and the "curve to save the country" market access strategy is also a good strategy
for successfully "going to sea".

According to the global drug pricing and access database, there are obvious differences in the average reimbursement time and average treatment cost of the same drug in different national markets
.
In the case of O-Drugs, the average medicare reimbursement duration in Spain is the same as in Canada (41 months), while in Australia and Germany it is relatively short (36 months and 38 months).

Based on the scientific analysis of business opportunities and access risks, enterprises should comprehensively consider the commercial potential, access risks and purchasing power of the target countries to formulate a scientific order
of access.
The best for you is the best, and you can prioritize markets
where the expected trial data can realistically meet their clinical needs.
Taking Singapore as an example, as one of the five founding members of ASEAN, its rapid economic development and excellent medical level and scientific research and innovation capabilities, in addition, small language barriers are also more conducive to pharmaceutical companies to communicate with local regulators and establish an international research and development system, if Singapore is used as a breakthrough, and then enter more ASEAN countries, and then impact the developed markets of Europe and the United States, it may "overtake in a curve"
.
In short, compared with the "thousands of troops" crowded in the "single wooden bridge" to the United States, with an agile access strategy to look at the broader market, it may be a more suitable choice
for most pharmaceutical companies.

Global Drug Pricing and Access Database

Having gone out on the expedition, he will surely travel far

Having gone out on the expedition, he will surely travel far

Existing experience shows us that without the support of the international market, it is difficult for high-value innovative drugs to achieve economies of scale and develop and grow
.
Therefore, if local innovative enterprises want to truly narrow the gap with their international advanced counterparts and gain the right to speak, no matter how long and tortuous the process of "going to sea" is, it is the only way to
"open the bow and have no turning back".

It is true that not all local innovative pharmaceutical companies have sufficient resources to support international research and development, but when low-cost me-too drugs are "struggling" in the international market with little clinical demand, the same variety or more indications, "going to sea" has become more and more "the game of the strong"
.
For the strong, compared with being squeezed by domestic market competition, "going to sea" should be an active choice
that has confidence in the competitiveness of their own products.
This confidence stems not only from the quality controllability, safety and efficacy of the drug, but also from the "value" it can bring to the target market, including multi-dimensional evidence including economic value, clinical value, social value, etc.
, which is the key to the successful access and commercialization of drugs, and MRCT that can represent more patient populations will undoubtedly provide strong support
for the evidence preparation of enterprises.

MRCT, which represents a larger patient population, will undoubtedly provide strong support for the preparation of the evidence for the enterprise
.

It is not terrible to encounter obstacles, it is important to learn from the obstacles and calm down and wait for a "willow dark flower"
.
Innovation is not easy, and the road to "going to sea" is not a smooth road, but since it has gone out, it will definitely travel a long way
.
When more and more enterprises sink their hearts into doing "source innovation" and take steps to lay out international research and development, I believe that more innovative drugs with international quality standards and international market recognition will emerge in the future, and local innovative pharmaceutical companies that have stepped through the "kan'er" will eventually usher in their own "dawn on the sea"
.