The Pharmaceutical Industry at a Glance Approval Status of Drugs for Unmet Medical Needs

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Shinji Tsubakihara, Senior Researcher, Pharmaceutical and Industrial Policy Research Institute

1. Introduction

Based on the results of a survey on medical needs conducted by the Human Science Foundation (hereinafter referred to as "HS Foundation" ⁾¹⁾, the Pharmaceutical Industry Policy Institute compiles data on new drug approvals and development pipelines and continuously analyzes the status of pharmaceutical companies' efforts to address unmet medical needs2)3 ⁾. ²⁾³⁾.

This report analyzes the new drugs approved from January 2019 to the end of December 2021, which were covered in the report of the Policy Research Institute News No.66 (July 2022) ^{3) ,} in addition to the new drugs newly approved in 2022, and also focuses on the malignant tumor disease area, where the number of approved drugs has been increasing in recent years. In addition, we also analyzed the number of approved drugs in the area of malignant neoplastic diseases, where the number of approved drugs has been increasing in recent years, in three periods from January 2014 to December 2022.

2. number of new drugs approved by treatment satisfaction and drug contribution

Figure 1 plots diseases along treatment satisfaction (horizontal axis) and drug contribution (vertical axis) for 60 diseases selected in the 6th HS Foundation survey reported in 2019 as "serious diseases," "diseases that significantly impair QOL," "diseases with a large number of patients," "diseases with high social impact," etc. 2019 -The ^number of new drugs approved in Japan for 60 diseases during the four-year period from 2019 to 2022 is shown by the size of the circle and the numerical value.

New drugs are defined as those approved as "drugs containing new active ingredients," "new indications," "new regenerative medicine products," or "additional indications for regenerative medicine products.

The total number of approved drugs during this period was ^4314)5), and 181 drugs (including those with multiple indications in one approval) and 140 products were approved for the 60 diseases in the HS Foundation survey. Of these, 73 (69 products) were new molecular entities (NMEs), accounting for 40.3% (73/181).

Of the 181 NMEs, 74 (59 products) were approved by domestic companies and 107 (81 products) by foreign companies.

The number of new regenerative medicine products related to the 60 diseases was 8 products (5 products), as 3 products of CART cell therapy were approved for malignant lymphoma in 2022 in a single change, 1 product was approved for an expanded indication, and 2 products were approved for an easing of requirements for patients already approved for the disease.

Looking at the number of approved products related to 60 diseases by quadrant, the percentage of new products approved for diseases in the first quadrant, where both treatment satisfaction and drug contribution are 50% or higher, was 87.8% (159/181), up from 85.7% in the previous survey, and new drug approvals were further concentrated in disease areas where both drug satisfaction and drug contribution were high. New approvals were further concentrated in disease areas where both drug satisfaction and contribution were high. In particular, many drugs were approved in the area of malignant tumor diseases, with 25 approved for "malignant lymphoma," 16 for "lung cancer," 14 for "leukemia," 10 for "breast cancer," 8 for "colorectal cancer," 6 for "liver cancer (hepatocellular carcinoma)," 5 for "prostate cancer," 3 for "stomach cancer," 2 for "cervical cancer," and 2 for "cervical cancer. and most of them (56.0%, 89/159) are drugs for malignant tumors in the first quadrant, and in 2022, 29 new drugs were added to the list of drugs for malignant tumors within 60 diseases. As for the number of approved drugs in quadrants 2, 3, and 4, 6 (3.3%), 7 (3.9%), and 9 (5.0%), respectively.

3) Approval trend of drugs for malignant tumor in 60 diseases

Following the analysis ⁽ Policy Research Institute News No. 663 ⁾, we focused on drugs for the treatment of malignant tumors.

Figure 2 shows the percentage of new drugs approved since April 2009 for 60 diseases in 10 malignant oncology disease areas (malignant lymphoma, leukemia, lung cancer, stomach cancer, colorectal cancer, liver cancer, pancreatic cancer, prostate cancer, breast cancer, and cervical cancer) in 2009-2011, 2014 -The number of approved products related to 60 diseases increased to 110, 124, 133, and 146, respectively. The number of new drugs approved in the 10 malignancy areas increased over time to 28, 45, 62, and 76, or 25.5%, 36.3%, 46.6%, and 52.1%, respectively, of the total, with malignancy treatment products accounting for more than half of the total. Looking at the average treatment satisfaction and drug contribution for the 10 malignant neoplastic diseases in the 2009, 2014, and 2019 HS Foundation surveys, both values increased over time, with particularly large increases in drug contribution.

4) Approval transition of drugs for malignant tumor by category

To investigate the factors contributing to the increase in the number of approved drugs for the treatment of the 10 malignancies in recent years, we focused on molecular-targeted drugs and antibody drugs and explored the increase or decrease in these drugs. Going back to 2014, when the results of the 5th HS Foundation ^survey6) were reported, the years 2014-2016 were designated as the "mid-2010s," 2017-2019 as the "late 2010s," and 2020-2022 as the The number of new drugs approved in each of these three years was classified into the categories of "molecular-targeted drugs," "antibody drugs," and "other anticancer drugs," and the number and percentage of approvals for each year were examined (Figures 3 and 4). Five "regenerative medicine products" were excluded from the analysis.

Molecularly targeted drugs" covers tyrosine kinase inhibitors, KRAS inhibitors, BRAF inhibitors, MEK inhibitors, mTOR inhibitors, cyclin-dependent kinase inhibitors, PARP inhibitors, proteasome inhibitors, and BCL-2 inhibitors, which are known as molecularly targeted drugs, that were approved during this period. Antibody drugs" included recombinant antibody drugs and antibody drug conjugate (ADC) drugs. Other Anticancer Drugs" included drugs for malignant tumors with cytotoxic effects, hormone disrupting effects, and metabolic disrupting effects.

The number of approved drugs in the three categories remained unchanged at 45 in both the mid-2010s (hereafter referred to as "mid-decade") and late-2010s (hereafter referred to as "late-decade"), but the number of approved drugs in the early 2020s (hereafter referred to as "early 20s") increased significantly to 71 (Figure 3 -A). Looking at the transition by category, the number of "molecular-targeted drugs" increased over time from 10 to 18 to 27, with 22.2%, 40.0%, and 38.0% of the total, respectively. The number of "Antibody drugs" increased from 10 to 19 to 27, and the percentages were 22.2%, 42.2%, and 38.0%, respectively. Other anticancer drugs" went from 25 to 8 to 17, with percentages of 55.6%, 17.8%, and 23.9%, respectively.

Next, we analyzed the trends by category to determine whether the increase in the number of approved drugs for malignant tumors was due to an increase in NMEs or to additional indications.

While the number of NMEs in the three categories remained stable in each period, the number of additional indications increased linearly for "molecular-targeted drugs" and "antibody drugs" (Figure 4). This suggests that the increase in the number of approved NMEs for the treatment of malignant tumors in recent years was largely due to additional indications.

An analysis of the approval of additional indications in each category shows that during the nine-year period from 2014 to 2022, 32 new indications were approved for 23 products in the "Molecular Targeted Drugs," 42 new indications were approved for 17 products in the "Antibody Drugs," and 30 new indications were approved for 23 products in the "Other Anticancer Drugs," for a total of 23 products. The products are listed by category in descending order of the number of additional approvals (Figure 5). Many antibody drugs received approval for multiple additional indications. The top three immune checkpoint antibody drugs (nivolumab, pembrolizumab, and atezolizumab) were the main reasons for the large number of additional indications for antibody drugs, with these three drugs accounting for approximately 40% of the total number of additional approvals. These three antibody products received priority review, and some products received orphan drug approval for "relapsed or refractory classical Hodgkin's lymphoma" and "advanced small cell lung cancer," which gave them preferential treatment under the Pharmaceutical Affairs Law.

Number of Approved Drugs for Malignant Tumors by Domestic and Foreign Investments

Companies applying for approval of malignancy drugs for the 10 malignancies were divided into domestic and foreign companies, and the number of approvals in the mid-decade, late-decade, and early-decade was analyzed (Figure 6). For malignancy drugs as a whole, the number of items approved by domestic companies increased in the early 20s, while the number of items approved by foreign companies in the same period increased approximately 2.5-fold compared to the mid-10s.

By category, foreign firms accounted for a large share of the "molecular-targeted drugs" market for the entire year, but the number of approvals for domestic firms also grew over time. In the "Antibody drugs" category, both foreign and domestic investment grew, with domestic investment dominating the market share for the full year.

Summary and Discussion

Overlaying the new drugs approved in Japan during the four-year period 2019-2022 along the treatment satisfaction (horizontal axis) and drug contribution (vertical axis) for 60 diseases in the 6th HS Foundation survey, the percentage of approved drugs in the first quadrant, where both treatment satisfaction and drug contribution were 50% or higher was 87.8%, which was further concentrated in the first quadrant during the year 2022. In particular, items for therapeutic agents for malignant tumors accounted for about 60% of the items in the first quadrant, and about half of the new drugs for 60 diseases in the last three years were therapeutic agents for malignant tumors.

In order to investigate the recent increase in the number of drugs for malignancies, the fifth HS Foundation survey was divided into three phases over the nine-year period from 2014 to 2022, when the survey was conducted, and drugs for 10 malignancies (malignant lymphoma, leukemia, lung cancer, stomach cancer, colorectal cancer, liver cancer, pancreatic cancer, prostate cancer, breast cancer and cervical cancer) were The number of approved items was classified by category and analyzed backward-looking. The reason for the large increase over time in the number of "molecular target drugs" and "antibody drugs" was that the number of additional indications approved had a greater impact than the number of NMEs approved. In particular, the number of approvals for immune checkpoint antibody drugs was particularly high, and drugs that target molecules commonly expressed by tumor cells, such as PD-1, to enhance the anti-tumor effects of autoimmunity were considered to have more opportunities to expand their indications. In addition, many intracellular signal transduction inhibitors are known as molecular-targeted agents, and some molecular-targeted agents have been approved for additional indications for multiple malignant tumors with common genetic mutations of signaling molecules, even if the primary organs are different.

As shown in Figure 2, the increase in the number of malignancy drugs over time was accompanied by an increase in treatment satisfaction and drug contribution in the HS Foundation survey, suggesting that advances in therapeutics and the increase in the number of therapeutic drugs have contributed significantly to the clinical practice of malignant neoplastic diseases. However, a closer look at the results of the Treatment Satisfaction and Drug Contribution ^{Survey1) (} Figure 7) for 60 diseases shows that even for diseases in the high quadrant of treatment satisfaction and drug contribution, such as in the area of malignant neoplastic diseases, few respondents actually answered that "drugs are contributing sufficiently. It can be said that unmet needs still exist in all disease areas.

The survey found that the pharmaceutical industry continues to provide treatment opportunities for malignancies with drug-resistant genetic mutations that have not been adequately addressed, as well as for patients who do not meet the indications for treatment. In addition to the development of "breakthrough new drugs," it is an important social responsibility of pharmaceutical companies and the pharmaceutical industry to expand the indications and indications of existing drugs and to respond to the unmet medical needs of patients.

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