Looking at the situation of FDA-approved drugs in the past 10 years, we can glimpse the innovation capabilities of the top 20 pharmaceutical companies worldwide and see into the future.

Understanding research trends and grasping research directions, this week Drug Discovery Today published an analytical article discussing the new drug development dynamics of the top 20 pharmaceutical companies in the United States approved by the FDA in the past decade (2014-2023). Analyzing the 10-year data to assess the level of innovation and evaluate the innovation capabilities of major pharmaceutical companies. Data does not lie, time witnesses everything! Over the past decade, the overall number of new drugs approved for top pharmaceutical companies has decreased. In the past decade, the top 20 leading pharmaceutical companies had 176 newly approved drugs by the FDA; another 33 were acquired by top pharmaceutical companies after approval; these top pharmaceutical companies introduced a total of 83 first-in-class new drugs in the past decade; the most approved new drugs by the top 20 pharmaceutical companies were in the field of oncology; the share of research and development output by major pharmaceutical companies decreased from 72% in 2014 to 40% in 2023; however, who is losing their research and innovation advantage, and as a result, losing the ability to maintain competitive advantage? Which leading companies continue to dominate in certain treatment areas? Over the past 10 years, the research and acquisition output of the top 20 pharmaceutical companies The table below shows the number of new drugs that have been approved by the FDA and brought to market by the top 20 pharmaceutical companies globally in the past decade (2014-2023). It can be seen that some leading companies have shown decline, while others continue to have output almost every year, with impressive achievements, such as Novartis, Lilly, AstraZeneca, Sanofi, Johnson & Johnson, Gilead, MSD, Pfizer, Roche, and others. Innovation competitiveness In the past 20 years, it seems that research and development (R&D) productivity in the pharmaceutical industry has been continuously declining. In the pharmaceutical industry, a pharmaceutical company's competitiveness and growth are directly related to its innovation capability. R&D investment refers to expenses in drug discovery and development; R&D output refers to the number of new drugs approved; R&D outcomes refer to the medical and economic value of new drugs. Only with sufficient R&D productivity can pharmaceutical companies continuously launch new drugs with competitive advantages. How is "innovation" defined in the pharmaceutical industry? In the context of drug innovation, differentiation is a manifestation of innovation, including structural, pharmacological, efficacy, or pharmacokinetic novelty of new drugs. Furthermore, innovation can also be defined as the process of integrating technological development of products with market introduction. This defines innovation from the specific result level of the process. For the pharmaceutical industry, after a pharmaceutical company undergoes a significant amount of drug research and development, a new drug approved by the FDA is considered innovative, a specific result of the process. Therefore, typical indicators for measuring the success of a pharmaceutical research organization include: the number of new drug approvals (R&D output), R&D expenditure per approved new drug (R&D efficiency), or R&D return levels (R&D effectiveness). The number of FDA-approved drugs is an essential indicator of a pharmaceutical company's innovation capability, and FDA defines innovation as: a new drug (or new treatment regimen) eligible for approval by the Center for Drug Evaluation and Research (CDER). In specific terms, a new molecular entity (NME) or a new therapeutic biological product (NTB) refers to a new active drug ingredient that has never been approved or marketed in the United States. Innovation Metrics The degree of innovation or novelty of a new drug depends on its differentiation from existing treatment methods. For first-in-class drugs, can they really provide higher therapeutic value? This is questionable. However, they represent significant scientific progress and are synonymous with pharmaceutical innovation. Similarly, the FDA also considers the degree of differentiation of new drugs during the approval process. For example, the FDA provides priority review beyond standard processes. This requires new drugs to show significant improvements (in safety or effectiveness) compared to existing therapies, exhibiting a higher level of differentiation, qualifying as breakthrough innovation. In addition, the FDA has various accelerated regulatory pathways, such as Fast Track, Accelerated Approval, Breakthrough Therapy Designation, and others. These accelerated drug approval programs are not mutually exclusive; if a new drug is approved through multiple accelerated programs, it indicates a higher level of innovation. Therefore, if a new drug is distinguished by the FDA, or is a first-in-class drug approval, or has multiple accelerated approvals, it indicates a high level of innovation. The above also provides several analysis metrics for analyzing a pharmaceutical company's research output and innovation capability over an extended period: FDA new drug approvals, first-in-class drug approvals, priority reviews, accelerated or breakthrough innovation approvals, etc. The table below shows the total number of new drugs obtained by the top 20 pharmaceutical companies through self-research or acquisition approvals in the past 20 years. These new drugs are further classified into: first-in-class drugs, new molecular entities, new therapeutic biological entities, priority reviews, orphan drugs, breakthrough innovations, accelerated approvals, and other subcategories. From 2014 to 2023, the FDA approved 176 new drugs for the top 20 pharmaceutical companies globally; these leading pharmaceutical companies also acquired an additional 33 new drugs after approval. According to the form of drugs, these new drugs include 130 new molecular entities (NMEs), 75 new therapeutic biological products (NTBs), and 4 oligonucleotide/antisense molecules. Overall innovation output of the top 20 pharmaceutical companies is declining In the figure below, the share of new drugs approved by the FDA from the top 20 pharmaceutical companies over the past 10 years has been declining, from 71% in 2014 (29 out of 41) to only 40% in 2023 (22 out of 55). During these 10 years, including acquisitions made after approval, the top 20 pharmaceutical companies produced a total of 209 new drugs, averaging one new drug per company per year. However, there are significant differences between companies. In terms of total output: First: Novartis, with 19 self-developed and 4 acquired, averaging 2.3 new drugs annually, and the only company to have self-developed products every year; Second: AstraZeneca, with 16 self-developed and 5 acquired, averaging 2.1 new drugs annually, with only two years without self-developed products (2016, 2019). (Note: The translation may not be perfect, but I have rendered the text as accurately as possible.)Third: Pfizer, independently developed 15 drugs and acquired 3, with an average output of 1.8 drugs per year. There were only 3 years with no independent development output (2014, 2020, 2021); Fourth: MSD, all output is from independent research, with 15 drugs, and an average output of 1.5 drugs per year. There were only 3 years with no independent development output (2020, 2022, 2023); Fifth: Lilly, independently developed 13 drugs and acquired 1, with an average output of 1.4 drugs per year. There was only 1 year without independent development output (2021); Sixth: Roche, independently developed 10 drugs and acquired 4, with an average output of 1.4 drugs per year. There were only 3 years without independent development output (2016, 2018, 2021); Seventh: AbbVie, independently developed 7 drugs and acquired 6, also the strongest purchasing power among pharmaceutical companies, with an average output of 1.3 drugs per year. There were 4 years without independent development output (2015, 2020, 2022, 2023); Eighth: Novartis, independently developed 8 drugs and acquired 4, with an average output of 1.2 drugs per year. There were 5 years without independent development output (2016-2019, 2021); Ninth: Johnson & Johnson, independently developed 10 drugs and acquired 1, with an average output of 1.1 drugs per year. There were only 2 years without independent development output (2016, 2020); Tenth: GlaxoSmithKline, independently developed 8 drugs and acquired 2, with an average output of 1 drug per year. There were 4 years without independent development output (2016, 2017, 2019, 2022); The remaining 10 companies had output lower than the average of 1 drug per year, with AstraZeneca (average 0.4), Bayer (average 0.4), and Sanofi (average 0.3) being the lowest. In terms of innovative drugs: As shown in the detailed table in the previous unit, the top 20 pharmaceutical companies have jointly launched 83 innovative drugs. From 14 drugs in 2014, the number decreased to 7 in 2023, showing a downward trend overall. At the company level: The companies with the most innovative drugs are Novartis (9/23), AstraZeneca (8/21), MSD (8/15), Novo Nordisk (7/12), Roche (6/14), and Johnson & Johnson (6/11). The companies with the highest proportion of innovative drugs in their output are Amgen (71%), Sanofi (67%), MSD (58%), BMS (60%), Johnson & Johnson (55%), MSD (53%), AstraZeneca (50%), Gilead (50%). The rest have proportions below 50%, with AbbVie (23%), Lilly (21%), and Takeda (11%) having the lowest proportion of innovative drugs. In terms of priority review: Most of the 209 new drugs produced by the top 20 pharmaceutical companies were approved through priority review (131 in total, accounting for 63%). The companies with the most drugs approved through priority review are Novartis (15/23), Roche (12/14), AstraZeneca (11/21), Pfizer (10/18), and MSD (10/15). In terms of orphan drug approvals: A total of 102 orphan drugs were produced by the top 20 pharmaceutical companies, accounting for 48.8%. The companies with the most orphan drugs are AstraZeneca (12/21), Novartis (11/23), and Roche (10/14). In terms of breakthrough therapy approvals: A total of 75 new drugs have been approved for breakthrough therapy, accounting for 35.9%. The companies with the most output are Roche (9/14), Novartis (8/23), AstraZeneca (6/21), and Pfizer (6/18). In terms of accelerated approval: A total of 41 new drugs have received accelerated approval qualifications. The companies with the most qualifications are Roche (6/14), Novartis (4/23), AstraZeneca (4/21), Johnson & Johnson (4/11), and Lilly (4/14). Overall, although the innovation output of the top 20 pharmaceutical companies is declining, there are still several leading companies that maintain strong competitiveness in terms of new drug output, innovative drugs, priority review, breakthrough therapy, orphan drugs, and accelerated approval. Notable examples include Novartis, AstraZeneca, and Roche. Distribution of Target Types and Therapeutic Areas As shown in the chart above, the most approved therapeutic area for new drugs by the top 20 pharmaceutical companies is oncology (80 drugs, 38.3%), followed by infectious diseases (28 drugs, 13.4%), neurology (19 drugs, 9.1%), cardiovascular diseases (18 drugs, 8.6%), and immunology (12 drugs, 5.7%). Some leading pharmaceutical companies have achieved significant success in specific therapeutic areas. BeiGene has launched three new drugs in the field of neurology (100% of BeiGene's new drugs approved). Gilead has 87.5% in infectious diseases, antiviral areas; J&J has 63.6% in oncology; Novo Nordisk has 60% in metabolic diseases/endocrinology; Novartis has 57% in oncology; BMS has 50% in oncology; Lilly has 50% in oncology; Pfizer has 50% in oncology; Roche has 50% in oncology, among others. In terms of first-time drug applications, the top 20 pharmaceutical companies have introduced 30 new drugs in the field of oncology (36.1%), 13 new drugs in cardiovascular diseases (15.7%), 10 new drugs in infectious diseases (12%), and 8 new drugs in neurology (9.6%). The remaining 22 new drugs are distributed in other 7 therapeutic areas (26.5%). Distribution of Target Types: The chart below shows the approval status of new drugs by the top 20 pharmaceutical companies categorized by drug target type. From 2014 to 2023, kinases (23%) are the most prominent target category for new drugs. Other enzymes (21%), G protein-coupled receptors (18%), and other receptors (17%) are also relevant biological target categories. Conclusion and Prospects The decrease in the number of newly approved drugs by these leading pharmaceutical companies, as well as the decline in related innovative capabilities, may be related to R&D project cutbacks in some cases. Although R&D expenditures have generally increased in recent years, this may also be related to the distribution of available R&D investments being less successful. If the leading pharmaceutical companies continue to lag in R&D innovation, maintaining their competitive advantage and filling the gap in...The ability to benefit from the expiration, ensure long-term market success, and maintain their business model will all be questioned.The complexity of science, stricter regulations, and higher processing standards are common reasons for the decline in research and development productivity. However, as the number of new drugs approved by non-Top 20 pharmaceutical companies continues to increase, there may be other factors affecting the output of leading pharmaceutical companies, including: 1. The trend of early pipeline reduction (stop-loss, focus on investment) leading to fewer approvals; 2. The shift from investing in scientific/discovery research to drug development; 3. Lack of "organizational efficiency"; 4. Past poor strategic decisions; 5. Frequent changes in R&D strategic positioning, leading to insufficient absorptive capacity in the fiercely competitive R&D field for the company; 6. Over-focus on traditional technologies, leading to missed opportunities for new technologies. The decline in the creation of new drugs is difficult to explain, but there are some reasonable factors, including: - The scientific complexity and resource intensity of research required to identify new, viable, and safe targets for drugs; - The focus of the pharmaceutical industry's R&D is on risk reduction strategies, prioritizing same-class best options rather than pioneering new drugs. Regardless of the future research results, the above analysis logic points out three key driving factors for pharmaceutical success: breaking path dependence, acquiring absorptive capacity, and establishing dynamic capabilities. Research also indicates that less successful companies need to abandon traditional technologies, enhance their absorptive capacity for new technologies, and improve their dynamic capabilities to better utilize external innovation. By combining these methods, R&D efficiency and effectiveness will be improved, leading to the development of more innovative new drugs. This article is reposted from the WeChat public account ""; Edited by GMTEight: Yan Wencai.