Since entering the march annual reporting season, many white horse stocks have experienced a shocking slippery slope, superimposed on the "Cinda ODAC incident" and the impact of the epidemic on the Shanghai Innovative Drug Center... Confidence in the entire innovative drug industry needs to be boosted.
The chain of "R&D-sales" cannot be broken. In the current environment, choose BD to go to sea, products directly to the sea, or strengthen domestic sales force? In these major issues related to the survival of innovative pharmaceutical companies, many companies are looking for an optimal solution.
Overseas licensing is the choice of many innovative pharmaceutical companies in recent times. Since March, Henlius, Hebo Pharmaceutical, Jinfang Pharmaceutical, Boaoxin Biological, etc. have signed BD large orders and withdrawn funds in advance.
There are also companies that choose to let their products go directly to sea. On April 11, BeiGene announced that the final results of a global Phase 3 clinical trial of the BTK inhibitor zebutinib were announced: in a study treating adult patients with relapsing refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), the overall superiority was superior to the control drug ibutinib. At present, zebutinib has been approved in 45 countries and regions around the world.
The updated data from this clinical trial means that zebutinib has once again confirmed its potential as the world's "best-in-class" BTK inhibitor in a "head-to-head trial".
The results of the CLL approval that challenged ibltinib's core market will be implemented in October
Ibutinib is currently the seventh largest variety in terms of global sales, selling $9.777 billion in 2021.
CLL, also known as "slow shower" in China, is the main battlefield of the BTK inhibitor market. In the 2019 CLL/SLL treatment guidelines published by the National Comprehensive Cancer Network, ibutinib monotherapy was the only recommended regimen of choice among all first-line treatment options.
In April 2020, ibutinib was approved for the 11th indication in the United States. At that time, there were institutional statistics, and 6 of the indications were in the field of slow lymph.
The full-strength layout of ibutinib on slow lymph is inseparable from the characteristics of European and American patients. Wang Xin, director of the Department of Hematology of Shandong Provincial Hospital, once introduced: "Slow lymph is the most common type of adult leukemia in Western countries, and the incidence of Westerners is about 4-5/100,000 people. ”
BeiGene can directly cut into the core field of ibutinib by relying on "head-to-head testing".
In June 2021, BeiGene disclosed that the Zebutinib Phase 3 ALPINE study reached the primary endpoint. On April 11 this year, the company gave further specific data in the disclosed final remission assessment: after the independent review committee assessed, the total remission rate orr of zebutinib in the treatment of slow and small lymph had reached 80.4%, higher than the 72.9% of the ibrutinib group, showing efficacy.
In this regard, Wang Lai, head of global research and development at BeiGene, also said: "Overcoming the recurrence and treatment resistance of CLL is the most difficult challenge faced by patients and clinicians, and the results of this updated evaluation demonstrate the potential of zebutinib for CLL." ”
The ALPINE head-to-head trial is one of 35 clinical trials of zebutinib conducted worldwide, recruiting 652 patients in many countries and regions such as Central, European, American, Australian and New Zealand, with the median follow-up time of more than two years.
In 2019, zebutinib was first approved for marketing in the United States, and since then it has been approved for multiple lymphoma indications in dozens of countries. This is also the second "head-to-head" trial of zebutinib directly against ibltinib.
Head-to-head, it means that the two sides are short and close, 1V1 heads-up. This kind of experiment is expensive and risky, because once it fails, no one will believe it anymore, and it is difficult for drugs to be approved, so in the past few domestic companies carried out head-to-head research. This year's Cinda Biological PD-1 Xindili monoclonal antibody, which failed to go to sea, was required by the FDA to make up for the head-to-head global multi-center trial.
According to the rules of the US FDA, on October 22 this year, Zebutinib in BeiGene will also receive the results of the review of the new indications for CLL, and experts will decide whether they can be approved for the treatment of new indications for chronic lymph in the United States.
The internationalization of sales in the 10 billion market has just started
For many years, BeiGene has been giving the outside world the impression of "burning money" and investing thousands of dollars in research and development.
According to the 2021 annual report, BeiGene's research and development expenses were US$1.46 billion, or about 9.5 billion yuan.
In fact, the focus of R&D is Phase 3 clinical, especially global studies. According to BeiGene's annual report, the company currently conducts more than 100 clinical trials in 45 countries around the world, with a total global enrollment of more than 14,500 people. Among them, the number of large-scale Phase 3 clinical trials is 38. The cost of head-to-head trials is more complex, in addition to the cost of the test, but also to buy a control drug, which is naturally a big expense.
So, can a large investment in global R&D experiments translate into benefits in the future?
Taking zebutinib as an example, the above-mentioned Phase 3 ALPINE clinical study in BeiGene has been opened in 2019, and this investment is exchanged for the opportunity to divide the nearly ten billion US dollar market of ibrutinib.
According to the convention, once the US market is broken, especially with head-to-head research data, the recognition in various countries and regions will be high. Zebutinib has successfully landed in 45 countries and regions around the world.
Everyone is eyeing the FDA, which is a helpless choice in the current global pharmaceutical landscape, after all, once the challenge is successful, the benefits are huge. Unlike the previous years, which generally used the FDA as a sign to decorate the façade, it is really necessary to see the hard power gap when it comes to the listing approval process.
Fortunately, the gap is narrowing little by little, and Chinese pharmaceutical companies have begun to touch the threshold of the FDA.
However, after the "globalization of research and development", innovative pharmaceutical companies still have to face the problem of "sales globalization".
The launch of China's innovative drugs in full swing today is only the first step in the internationalization process of Chinese pharmaceutical companies. This road will not be smooth, enterprises must have confidence and expectations, and the capital market must have expectations. For enterprises, what is more important is forward-looking prediction and strategic layout, as well as all-round preparation and investment on the road to sea.