In an effort to optimize profits from its flagship cancer medication, Keytruda, Merck & Co (also known as MSD) has implemented various strategies, including adjustments to recommended dosages and changes in vial sizes. However, experts in India argue that these measures have led to increased cancer treatment costs and resulted in patients receiving far more medication than necessary.
The Indian Express conducted discussions with prominent oncologists across India as part of a collaborative investigation with the International Consortium of Investigative Journalists (ICIJ). Their findings revealed that a corporate directive promoting standardized high doses, combined with a complex patient access system, has contributed to the emergence of a counterfeit market for Keytruda in several cities.
While many specialists preferred to remain anonymous, they unanimously expressed that, with generic versions of Keytruda not expected until 2028, a more effective strategy for patients would involve reduced dosages, shorter treatment plans, vial sharing, and collective procurement efforts.
Initially approved by the US Food and Drug Administration (FDA) in 2014 for metastatic skin cancer, Keytruda has since expanded its use to various types of cancer, generating projected sales of $29.5 billion in 2024. Recently, it was included in the World Health Organization’s model list of essential medicines as a first-line treatment for metastatic non-small cell lung cancer, cervical cancer, and colorectal cancer. This list assists countries in ensuring the availability of crucial medications in public health facilities and informs government procurement and insurance reimbursement policies.
The steep cost of Keytruda, however, poses a significant barrier for low and middle-income countries, including India, making widespread access challenging. A committee that recommended the drug’s inclusion on the essential medicines list acknowledged this issue, stating that “immune checkpoint inhibitors may not be viable treatment options for many countries due to their high costs, the necessity of companion diagnostics, and the potential financial strain on healthcare systems that could detract from other essential medicines.”
Dr. Atul Batra, an additional professor of oncology at AIIMS in Delhi, describes the situation as “financial toxicity,” where the exorbitant prices of cancer treatments make them inaccessible for the majority of patients.
One of the main concerns is the fixed high dosage of Keytruda. Upon its initial approval in 2014, the recommended dosage was set at 2 mg/kg every three weeks. By 2016, this changed to a uniform 200 mg every three weeks for all patients, irrespective of their body weight. Given that most Indians weigh between 55 and 65 kg, this standard dose results in excessive drug administration for many patients.
Experts assert that this uniform dosage leads to unnecessary financial burdens on patients, particularly in India. Dr. Batra explained that the fixed high dose was based on studies that focused on maximum tolerated doses, a method typically used in chemotherapy drug development. However, immunotherapy operates differently; it enhances the immune system’s ability to recognize and destroy cancer cells rather than directly killing them. Consequently, exceeding the biologically effective dose does not enhance treatment efficacy.
A study from 2017 highlighted that Keytruda’s initial clinical trials indicated complete target engagement with full saturation at just 1 mg/kg, lasting for at least 21 days. Subsequent research showed no difference in effectiveness between 3 mg and 10 mg per kg. Nevertheless, the fixed 200 mg dose, established during the Keynote-024 trial, became the standard following the FDA’s 2016 approval and has remained unchanged.
The WHO expert committee pointed out that weight-based dosing could sustain treatment effectiveness while reducing costs for non-small cell lung cancer, as evidenced by several retrospective studies conducted in multiple countries.
In India, although Keytruda is not part of the essential medicines list—which was last updated in 2022—a recent set of guidelines from the Directorate General of Health Services recommended the use of lower-dose pembrolizumab when the standard 200 mg dose is financially unviable or unavailable.
Dr. Batra conducted a study at AIIMS aimed at assessing the efficacy of a significantly lower dose than the original recommendation. His research involved 157 women with triple-negative breast cancer (TNBC), an aggressive type resistant to hormone therapy. Participants received either standard chemotherapy or chemotherapy combined with a flat 50 mg dose of Keytruda every six weeks, which is one-eighth of the recommended 200 mg dose.
The results were noteworthy: 53.8% of patients receiving Keytruda alongside chemotherapy showed no signs of invasive cancer, compared to 40.5% in the chemotherapy-only group. Among those who underwent surgery, 56.7% in the Keytruda group had no invasive cancer, in contrast to 41% in the chemotherapy-only group.
“Our findings indicate that administering a low 50 mg dose every six weeks can be as effective as the standard 200 mg dose every three weeks,” Dr. Batra stated. “However, there are no trials comparing the low-dose version directly against the full-dose version. Funding for such a trial remains a significant hurdle.”
Despite these promising results, two significant challenges hinder the broader adoption of low-dose treatment. Firstly, patients prescribed a 50 mg dose are unable to access Kiran, the company’s patient assistance program, which only covers the 200 mg dose, making the lower dose financially unfeasible for many. Secondly, Keytruda’s pricing structure and access barriers further complicate the implementation of lower-dose therapies.
