Keytruda Achieves 40th FDA Approval: First PD-1 Inhibitor for First-Line Treatment of Advanced or Recurrent Endometrial Cancer Regardless of MMR Status
MSD
Pharmaceutical R&D and Manufacturer
After becoming the top drug, K drug has not slowed down its pace.
Last year's sales were $25 billion, a year-on-year increase of 19%; in the first quarter of this year, sales reached $6.947 billion, continuing a high year-on-year growth of 24%.
As is known to all, the growth engine of Keytruda (K药) continues to remain robust, with the expansion of indications being the core reason. In the 10 years since its launch, it has received approval for 39 indications.
And on June 17, the FDA approved Keytruda (K药) in combination with chemotherapy for the treatment of primary advanced
In order to maintain growth and make the upcoming patent cliff as smooth as possible, MSD has been fully exploring the potential of Keytruda in recent years, continuously venturing into more fields. Last year, MSD's R&D investment reached 30 billion U.S. dollars, with a focus on developing Keytruda combination therapies in Phase 3 clinical pipelines.
According to MSD, there are currently over 1,600 trials studying the application of Keytruda (K药) in various cancers and treatment settings. This means that Keytruda may unlock even more indications in the future. This will not only continue to bring hope to countless patients but also add momentum for MSD.
Looking back at the path to dominance for K drug, it has been a continuous exploration of uncharted territories guided by science, built upon countless clinical trials, financial investments, and even failures. To some extent, there are no real secrets behind the success of this "King of Drugs," but precisely therein lies the revelation for the entire industry:
Only through continuous innovation and proving oneself with clinical data can one remain invincible in the fierce market competition.
Because, the growth of the innovative drug world is driven by people's perpetual health needs.
/ 01 / The 40th Indication
The Competition in the PD-1 Market: The Core Lies in Approved Indications.
In the first few years after their launch, K drug's indications were far fewer than those of O drug. In 2016, O drug had already been approved for use in multiple cancer types including melanoma, head and neck cancer, lung cancer, and renal cancer, while K drug was only approved for use in melanoma and lung cancer.
Clinically, O drug had nearly 20 clinical trials entering the phase III stage at that time, while K drug had only about 10, and most of them were lagging behind O drug in terms of progress.
However, Keytruda achieved a comeback against Opdivo with its victory in the first-line treatment of non-small cell lung cancer (NSCLC). Subsequently, it continued to expand its indications, further solidifying its position as the king of PD-1 inhibitors.
As of now, Keytruda has been approved for 40 indications in the United States, as shown in the Keytruda prescribing information below, covering 20 types of cancers including melanoma, lung cancer, liver cancer, and head and neck cancer, among which there are multiple first-line treatments.
The latest approved indication for endometrial cancer is the third indication for Keytruda (K药) in the field of endometrial cancer. According to MSD, this is also the first FDA-approved regimen combining Keytruda with chemotherapy for the treatment of primary advanced endometrial cancer.
This approval is mainly based on the results of a Phase III clinical trial (KEYNOTE-868/NRG-GY018). The primary endpoint of the trial was progression-free survival (PFS). Whether in the mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) population, treatment with Keytruda (K药) in combination with paclitaxel and carboplatin significantly improved PFS compared to placebo.
Specifically, in the dMMR cohort, the median PFS was not reached in the K drug combination therapy group, while the median PFS in the placebo group was 6.5 months; in the pMMR cohort, the median PFS was 11.1 months in the K drug combination therapy group and 8.5 months in the placebo group, with a statistically significant difference between the two.
MSD stated that endometrial cancer is now the most common gynecological cancer in the United States, and it is projected that by 2024, the number of deaths from this disease will surpass those from ovarian cancer. Unlike many other solid tumors, the survival rate for women with endometrial cancer has not improved over the past four years.
Currently, the standard first-line chemotherapy is paclitaxel plus carboplatin, and the latest performance of Keytruda combined with chemotherapy means that patients are facing a new first-line treatment option.
Overall, in 10 years, 40 indications have been approved, averaging four indications per year—K药 (Keytruda) has been nothing short of highly productive. From 2017 to 2020, six indications were approved each year, and in 2021, the number of approved indications even reached eight.
The speed and breadth of clinical indication development have supported the growth of Keytruda (K药) over the past decade. Continuously exploring combination therapies, delving into early-stage indications, and seeking new areas of growth have enabled Keytruda to remain highly competitive despite its already significant market base.
/ 02 / Maintain High Growth
Lung cancer is the stronghold of Keytruda.
As mentioned earlier, in 2016, Keytruda (K药) achieved a victory in the first-line treatment of NSCLC, which allowed it to surpass Opdivo (O药) and marked the beginning of its rapid rise.
In 2018, Keytruda (K药) sales officially surpassed Opdivo (O药), with Keytruda generating $7.171 billion in sales, while Opdivo reached only $6.735 billion. Keytruda's robust growth was primarily driven by its contributions in the lung cancer field, where revenue from lung cancer accounted for approximately 70% that year.
In the past few years, the strong growth of K drug has also been mainly contributed by the NSCLC indication. After its sales surpassed the 15 billion US dollars mark, it still maintained an annual growth of about 16%; the sales in the first quarter of this year were close to 7 billion US dollars, with a growth rate of 24%. Obviously, its growth "engine" is no longer limited to NSCLC.
Since 2021, adjuvant/neoadjuvant treatment-related indications have become a new growth engine for Keytruda. According to the 2022 annual report conference call, Keytruda's growth in the United States has mainly benefited from adjuvant/neoadjuvant treatments for cancers such as triple-negative breast cancer, renal cell carcinoma, and melanoma, followed by NSCLC. In markets outside the United States, although NSCLC remains the primary driver of Keytruda’s growth, adjuvant/neoadjuvant treatments for breast cancer and renal cell carcinoma are also strongly contributing.
In the first quarter of this year, according to MSD, the strong growth of Keytruda was mainly driven by the continued robust demand for early-stage and metastatic indications.
Specifically, the growth of Keytruda (K药) in the U.S. has been mainly driven by its use in adjuvant/neoadjuvant treatment for NSCLC and its indication for advanced urothelial carcinoma; whereas outside the U.S., the growth of Keytruda has been primarily fueled by demand for its use in triple-negative breast cancer, adjuvant/neoadjuvant treatment for renal cell carcinoma, and metastatic indications.
要知道，FDA only approved Keytruda (K药) in combination with platinum-containing chemotherapy as neoadjuvant treatment before surgery and as a single-agent adjuvant treatment after surgery for the treatment of patients with resectable NSCLC last year. This means that after the indication was approved for marketing, it got off to a strong start.
In fact, the tumor indications for adjuvant/neoadjuvant therapy have long become a new battleground for PD-1, and not only MSD but also pharmaceutical companies both in China and abroad are making arrangements.
Neoadjuvant therapy refers to the use of chemotherapy, radiotherapy, targeted therapy, and other methods to treat patients before surgically removing the tumor, while adjuvant therapy refers to treating patients after surgery to eliminate potential microscopic tumor cells.
For patients, adjuvant/neoadjuvant therapy is the key factor influencing survival cycles; for pharmaceutical companies, while bringing better treatment outcomes to patients, it also opens up a larger market space. This is because the target group in this field mainly consists of stage II/III cancer patients. Whether in the United States or China, the majority of newly diagnosed patients are at stage II/III.
No pharmaceutical company doesn't look forward to this market, and it is also becoming a new growth driver for Keytruda.
/ 03 / 10 Years of Insights from K Drug
To alleviate the pressure of the patent cliff, Keytruda has already made a broad layout in immunotherapy for early-stage tumors, covering common cancers such as lung cancer, liver cancer, and breast cancer. Previously, MSD projected that by 2028, approximately 40% of approved indications would be for adjuvant/neoadjuvant treatments, accounting for 30% of sales.
Whether the prediction can be realized or not, continuously expanding the indications for K drug and seeking sustainable growth momentum are things that MSD must do.
According to the information disclosed on the U.S. ClinicalTrials website, the number of clinical trials related to Keytruda (K药), including those that have not yet started patient recruitment (137) and those currently recruiting patients (836), has reached 973.
Looking further, as of the end of 2023, MSD had a total of 14 oncology pipeline drugs in Phase 3 clinical trials, with over 40% primarily focused on developing combination therapies with Keytruda (K药). This suggests that Keytruda may unlock even more indications in the future.
The high growth of K drug is closely related to the depth, breadth, and especially the number of clinical layouts by MSD. According to MSD, there are currently over 1,600 trials studying the application of K drug in various cancers and treatment settings, including its combination with ADC, oncolytic virus therapy, mRNA cancer vaccines, and other novel molecules.
This is not difficult to understand, as K drug has not always been successful in clinical expansion, such as its multiple failures in the field of prostate cancer and the consecutive setbacks of the Coke combination. The success of K drug today and the 40 indications behind it are the result of countless clinical trials, money, and even failures.
Compared to the number, the more important aspect lies in clinical strategy. In fact, during the development of Keytruda, there were no lack of innovative and highly significant trial designs.
The clinical beginning of K drug was KEYNOTE-001. Normally, a phase I clinical trial only involves dozens of participants, but KEYNOTE-001 involved over 1,000 patients in the phase I trial for melanoma, and it was approved for marketing based on these results. This approach was completely different from the traditional sequential clinical research design methods and became an example of accelerating the drug development process.
KEYNOTE-024 marked the turning point for K药's major comeback, demonstrating PFS benefits in first-line monotherapy for NSCLC with PD-L1 ≥50% based on the 001 trial, gaining an early advantage; subsequently, KEYNOTE-042 further confirmed K药's OS benefits in patients with PD-L1 ≥1%.
In the first-line combination therapy for NSCLC, the innovative Phase 1/1 design of KEYNOTE-021 enabled Keytruda to receive accelerated FDA approval in 2017; subsequently, KEYNOTE-189 and KEYNOTE-407 respectively validated the efficacy of Keytruda in patients with metastatic non-squamous NSCLC and metastatic squamous NSCLC.
Unlike 001's unconventional approach, the aforementioned trials progressed steadily through different stages of drug development, with varying endpoint populations/design choices, establishing K药's success and leading position in the NSCLC field.
In the field of early-stage indications, Keytruda (K药) also aims to establish its advantages by gaining insights into clinical needs and demonstrating excellent clinical capabilities. For example, in the perioperative treatment of NSCLC, although it was not the first to gain approval, it has the potential to overtake competitors later on. The clinical design of KEYNOTE-671 involves administering Keytruda combination therapy both before and after surgery to observe patients' clinical benefits. When compared with non-head-to-head clinical data from Opdivo (O药) and others, Keytruda shows a certain competitive edge.
Clearly, compared to the 40 indications, what is more noteworthy are the stories and insights behind these indications.
Throughout the development process of the entire indication, the correctness of efficiency and strategy ultimately determines the progress of a drug's market launch and the magnitude of its final commercial value. Of course, the root of whether efficiency and strategy can bring commercial value lies in the treatment efficacy.
From this perspective, the King of Medicine does not hold too many secrets. However, this is precisely where its revelation to the entire industry lies:
Only through continuous innovation and proving oneself with clinical data can one remain invincible in the fierce market competition.
Title: When MSD’s K Drug Unlocks Its 40th Indication