Date: 2016-08-08
Type of information: Granting of a Market Authorisation in the EU
Product name: Keytruda®
Compound: pembrolizumab (MK-3475)
Therapeutic area: Cancer - Oncology
Action mechanism:
- monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is an investigational, highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. MK-3475 is currently being studied in three clinical trials for advanced melanoma including a Phase III trial of MK-3475 versus ipilimumab in ipilimumab-naïve advanced melanoma patients (PN 006). Enrollment is complete in the advanced melanoma cohorts in the company’s Phase IB trial (PN 001) and the Phase II trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide. In April 2013, MK-3475 has received a Breakthrough Therapy designation for advanced melanoma from the FDA. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway.
Company: Merck&Co (USA - NJ)
Disease:
- - epidermal growth factor receptor (EGFR) mutation-negative, and anaplastic lymphoma kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy
- - patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express PD-L1
Latest news:
- • On 23 June 2016, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Keytruda®. The CHMP adopted a new indication as follows: "Keytruda® is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received approved therapy for these mutations prior to receiving Keytruda®."
- • On October 2, 2015, the FDA granted accelerated approval for Keytruda® (pembrolizumab) to treat patients with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1. Keytruda® is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.
Keytruda® works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda® may help the body’s immune system fight the cancer cells. Another drug, Opdivo® (nivolumab), manufactured by BMS, also targets the PD-1/PD-L1 pathway and was approved to treat squamous non-small cell lung cancer (a certain kind of NSCLC) in 2015.
- The safety of Keytruda® was studied in 550 patients with advanced NSCLC. The most common side effects of Keytruda® included fatigue, decreased appetite, shortness of breath or impaired breathing (dyspnea) and cough. Keytruda also has the potential to cause severe side effects that result from the immune system effect of Keytruda®.
- The effectiveness of Keytruda® for this use was demonstrated in a subgroup of 61 patients enrolled within a larger multicenter, open-label, multi-part study. The subgroup consisted of patients with advanced NSCLC that progressed following platinum-based chemotherapy or, if appropriate, targeted therapy for certain genetic mutations (ALK or EGFR). This subgroup also had PD-L1 positive tumors based on the results of the 22C3 pharmDx diagnostic test. Study participants received 10 mg/kg of Keytruda every two or three weeks. The major outcome measure was overall response rate (percentage of patients who experienced complete and partial shrinkage of their tumors). Tumors shrank in 41 percent of patients treated with Keytruda and the effect lasted between 2.1 and 9.1 months.
- In the 550 study participants with advanced NSCLC, severe immune-mediated side effects occurred involving the lungs, colon and hormone-producing glands. Other uncommon immune-mediated side effects were rash and inflammation of blood vessels (vasculitis). Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby. Across clinical studies, a disorder in which the body's immune system attacks part of the peripheral nervous system (Guillain-Barre Syndrome) also occurred.
- Keytruda® was approved under the agency’s accelerated approval program, which allows the approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms in patients being treated with Keytruda has not yet been established.
- • On October 27, 2014, Merck&Co announced that the FDA has granted Breakthrough Therapy Designation to Keytruda® (pembrolizumab) for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. This is the second Breakthrough Therapy Designation granted for Keytruda®. The Breakthrough Therapy Designation in advanced NSCLC is supported by data from the ongoing Phase 1b KEYNOTE-001 study, and updated findings were recently presented at the European Society of Medical Oncology (ESMO) 2014 Congress.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-10-02
UE authorization: 2016-08-08
Favourable opinion UE: 2016-06-23
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
