On Tuesday, May 23rd, the FDA granted accelerated approval to Merck & Co.’s Keytruda® (pembrolizumab), a product to treat cancers with a specific genetic feature (also known as a biomarker). Keytruda’s approval marks a big step for the Agency, as it is the first cancer treatment to be approved “based on a common biomarker rather than the location in the body where the tumor originated.”
In its recent press release, FDA states that Keytruda “is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.”
Keytruda was previously approved by the FDA to treat certain patients with “metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.”
Keytruda was approved for this new indication using the Priority Review designation via the Accelerated Approval pathway. The Agency’s Priority Review designation is grated to products that “if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.” This helps the Agency work toward its goal of reviewing and approving these applications within six months of submission.
FDA’s Accelerated Approval pathway allows the Agency to expedite the approval process of drugs for the treatment of serious conditions with an unmet need as long as the drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. FDA is requiring Merck to conduct additional studies to verify and describe Keytruda’s anticipated clinical benefits. The sponsor is currently in the process of conducting these studies in additional patients with MSI-H or dMMR tumors.
The abnormalities contained with MSI-H and dMMR tumors can affect the cells’ ability to properly repair DNA. Although these tumors are most commonly found in patients with colorectal, endometrial, and gastrointestinal cancers, they have also been found in patients with cancers arising in the breast, prostate, bladder, and thyroid gland, among others. FDA states that about “5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.”
The product targets the PD-1/PD-L1 cellular pathway, which are proteins found in the body’s immune cells as well as some cancer cells. By targeting and focusing on these cells, Keytruda is able to help the body’s immune system fight the cancer cells.
Merck & Co. demonstrated the safety & efficacy for this indication of Keytruda by studying patients with MSI-H or dMMR solid tumors. The participants were enrolled in one of five uncontrolled, single-arm clinical trials. Some of the clinical trials required patients to have MSI-H or dMMR cancers, while other trials had only a subgroup of patients with MSI-H or dMMR cancers.
Trial participants consisted of 149 patients with a total of 15 different types of cancer, the most common being colorectal, endometrial, and other gastrointestinal cancers. “The review of Keytruda for this indication was based on the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and for how long (durability of response). Of the 149 patients who received Keytruda in the trials, 39.6 percent had a complete or partial response. For 78 percent of those patients, the response lasted for six months or more.”
The most common side effects of Keytruda include:
In addition, FDA notes that “Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Complications or death related to allogeneic hematopoietic stem cell transplantation after using Keytruda has occurred.”
If patients experience severe or life-threatening infusion-related ractions occur, FDA recommends that they stop taking Keytruda immediately. FDA also advises women who are pregnant or breastfeeding not to take Keytruda, stating that it may cause harm to a developing fetus or newborn baby. Additionally, it is important to note that “the safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.”
May 25, 2017
May 2022 Guidance Document Download the Final Guidance Document The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Use of...
May 25, 2017
In the wake of the 21st Century Cures Act (December 2016), the FDA has switched gears to accelerate the development of novel therapies and speed up the review process, particularly in the field of...
May 25, 2017
In March 2011, the Tobacco Products Scientific Advisory Committee released a report on the impact of menthol on public health. Based on the committee’s review of all available evidence, they...