TOP14 R&D efficiency PK of pharmaceutical companies: Who is more efficient in independent R&D vs. external innovation?

The pharmaceutical industry is highly dependent on innovative growth

Recently, "Drug Discovery Today" magazine has conducted qualitative and quantitative analysis on the data of 14 leading pharmaceutical companies in the world's TOP20 companies, such as Roche, Pfizer, etc.

After researching 270 new molecular entities (NME) and 160,000 data, it is found that the R&D efficiency of these 14 companies seems to have declined, but the NME launched by them still occupies half of the industry

On the other hand, research has found that there is a "scale effect" in pharmaceutical R&D: large R&D institutions benefit from increased scale output and are more efficient and competitive than small companies

The usual measure of R&D efficiency is to divide R&D investment by R&D output (such as the number of approved new drugs, publication of papers, etc.

01 Two major standards: the number of new drugs approved and the publication of papers

The number of new drugs approved as the primary criterion for measuring R&D output is the most concerned data in the industry

From 1999 to 2018, the year with the largest number of new drugs on the market was 24 in 2014, followed by 21 in 2015

In the past 20 years, R&D investment has also shown a steady growth trend, from 49.

As one of the standards for measuring R&D output, the publication of papers has also attracted much attention

Between 1999 and 2018, 14 pharmaceutical companies published a total of 167,138 scientific papers

(Note: a represents the number of new drugs approved, b represents the cumulative impact coefficient)

Combining the above data, dividing the total R&D expenditure by the number of new drug approvals, and dividing the total R&D expenditure by the cumulative influencing factors, these two variables can be used to measure the R&D efficiency of these 14 companies.

Among them, Pfizer, Merck, Novartis, GlaxoSmithKline and Gilead have better R&D output, which means they are more efficient in R&D

02 Introduce VS self-research

It can be seen from the number of new drugs on the market that Pfizer, which focuses on external innovation, has 40 new drugs that far exceeds the number of self-developed Novartis’s 31

In 2020, Pfizer's R&D investment ranked fifth among the world's top ten pharmaceutical companies, with an investment of US$9.

The 2020 epidemic has led to a decline in the sales of many pharmaceutical companies' products, but Pfizer has made a lot of money by choosing to cooperate with the mRNA star company BioNTech

Novartis, which has consistently ranked second in the world, has been at the forefront of innovative therapies in recent years

For new drug innovation, Novartis adopts the kill the losers strategy, decisively abandon those zombie projects, sell them or simply abandon them, saving time and cost to support higher success rate or more promising projects
.
In 2017, Novartis launched Kymriah, the world's first CAR-T cell drug, marking the first year of CAR-T cell therapy
.
In the following three years, Kymriah's revenue gradually increased, and it began to become a new engine for Novartis' performance growth
.
At present, Kymriah has been approved for listing in 27 countries around the world, and there are already 290 CAR-T treatment centers, and it is expected to become one of the growth points in the future
.

In addition to holding the world's first CAR-T drug Kymriah, Novartis also has the world's most expensive drug-Zolgensma, a gene therapy for spinal muscular atrophy, but this acquired drug has recently caused Novartis to have a headache
.

Three years ago, Novartis spent US$8.
7 billion to acquire AveXis and obtained the high hope Zolgensma
.
At that time, in order to make the merger and acquisition the fastest to integrate, Novartis executives unanimously agreed to let AveXis president Dave Lennon (Dave Lennon) be responsible for the new gene therapy department, and fully invest in manufacturing
.
Although Zolgensma brought good income to Novartis, it did not meet Novartis's expectations.
This crisis emerged with the departure of Dave Lennon
.
Novartis had to reorganize its gene therapy department
.

It can be seen that although acquisition is a shortcut to "innovation", it also has risks
.

03 China R&D efficiency

Compared with global new drug research and development, China's new drug discovery stage is still in the "free rider" stage, so the research and development efficiency is higher
.

Taking the TOP10 R&D investment as an example, Hengrui Pharmaceuticals, BeiGene, and Zai Lab represent three models respectively.
Hengrui is an "independent R&D" party, Zai Lab is an "external innovation" party, and Baekje's degree is between Between the first two
.

E-pharmaceutical managers conducted an analysis based on a three-family model
.
Taking 2010 as a starting point to compare the development and innovation achievements of Hengrui and Baekje has certain reference significance
.
On the one hand, 2010 was the year that Baekje was established.
In the same year, Hengrui divided the original research institute into two according to the R&D focus: one research institute engaged in the development of innovative drugs, and the other research institute engaged in the development of generic drugs.
In August of that year, Hengrui Rui also established the Institute of Biology, specializing in the development of fermentation and protein drugs.
This year can be regarded as the "first year" of Hengrui Biopharmaceuticals
.
On the other hand, the cycle of new drug research and development is usually 10 years, especially when the new drug approval system before 2017 is not in line with international standards, it will take longer to study
.

From 2010 to the end of 2020, Hengrui’s R&D investment is about 18.
141 billion yuan (estimated value, the estimation method is the enterprise expense growth model), forming 10 publicly disclosed pipelines that have reached the NDA stage, and there are more than 40 models.
in the study of innovation and pharmaceutical products, targets covering CDK4 / 6, PD-L1, AR, VEGFR, BTK, PI3Kδ, HER2 ADC, JAK1 and so on
.
And 8 products that have been on the market, except for Irecoxib, which was launched in 2011, the main R&D investment for the remaining 7 products was during this period
.

In terms of technology platform, Hengrui has established a new technology platform with independent intellectual property rights, such as proteolytic targeted chimera (PROTAC), molecular glue, antibody-drug conjugate (ADC), bi/multispecific antibody, gene treatment, mRNA, bioinformatics, translational medicine and so on
.
Among them, 2 new and differentiated ADC molecules have been successfully approved for clinical use, and 3 ADC molecules have been approved for clinical use; 2 molecules for gene therapy have completed PCC and entered the preclinical development stage; the first domestic CTGF antibody has been approved for clinical use; PDL1 /TGFβ bispecific antibody drug SHR-1701 is rapidly launching phase III clinical research, the new generation of PD-L1/SIRPr fusion protein will soon be submitted for clinical research applications, and there are more than 10 First-in-class/Best-in-class double/ Multispecific antibodies are under development
.

In comparison, Baekje’s R&D investment in 2017-2020 alone exceeded 22 billion yuan, forming nearly 50 clinical stage candidates and commercial product echelons, including 12 models such as BTK, PD-1, and PARP.
Products that have been successfully commercialized (3 models independently developed by BeiGene); a number of differentiated pipelines under research have entered or will enter key clinical trials, including TIGIT, Bcl-2, PI3Kδ, OX40, HPK-1 , TIM3 and so on
.
At the same time, there are currently more than 50 preclinical projects in its pipeline, of which about half have Fist-in-class potential
.
More than 10 projects will enter the clinical stage in the next 24 months
.
According to incomplete statistics, during this period, BeiGene established a total of 26 international cooperation with companies such as Xinji, Amgen, Merck, and Eli Lilly
.

In the past two years, Zai Lab has gradually increased its investment in research and development
.
In the first half of this year, Zai Lab invested nearly US$350 million in R&D, an increase of 239% year-on-year, mainly for new business development payments related to Mirati and Macro Genics (both biopharmaceutical companies), all of which were recorded as R&D expenses
.
Since 2018, Zai Lab has invested approximately US$835.
2 million in R&D
.

On Zai Lab’s recent R&D day, its founder, Ying Du, stated that Zai Lab’s goal is to have more than 15 products on the market by 2025, covering more than 35 indications
.
Currently, Zai Lab's product pipeline includes more than 25 products, of which three products have been commercialized, and 12 products are in the late stage of development
.
In the semi-annual report, Zai Lab also disclosed the development progress of three self-developed products: IL-17 new human-derived nanobody, which is expected to release preliminary data interpretation of the global phase I study; and improved targeting CD47 to reduce effectors The functional humanized IgG4 monoclonal antibody ZL-1201 will determine the recommended phase II dose through the ongoing phase I clinical study; there is also the first disclosed ZL-2309 targeting CDC7, which will be launched before the end of the year 2 Proof-of-concept research
.
However, these three self-research projects are still in the early stages
.

At this stage, domestic pharmaceutical innovation and R&D are still at an early stage, but the "economies of scale" of R&D investment is obvious.
Only long-term continuous investment can produce R&D output, reduce risks, and become a truly large pharmaceutical company
.