FDA Approves 1st Drug to Treat Cancer Based on Genetics of Tumor, Not Location

May 25, 2017

FDA Approves Keytruda to Treat Patients with Solid Tumors

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’s History with FDA

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’s Latest Approval

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.

MSI-H & 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.”

How Keytruda Works

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.

Safety & Efficacy of Keytruda

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.”

Side Effects

The most common side effects of Keytruda include:

  • Fatigue
  • Itchy skin (pruritus)
  • Diarrhea
  • Decreased appetite
  • Rash
  • Fever (pyrexia)
  • Cough
  • Difficulty breathing (dyspnea)
  • Musculoskeletal pain
  • Constipation
  • Nausea

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.”

Are you in the process of developing a product for the treatment of a rare but serious condition?  Do you think your product is eligible for one of FDA's expedited approval programs? We can help get your products approved by the FDA.  To learn more about our services and how we can help you, contact us today.


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