Pembrolizumab that formerly named MK-3475 and Lambrolizumab with trade name Keytruda is a humanized antibody used in cancer immunotherapy. It was approved for the treatment of melanoma, certain subsets of colorectal cancer, head and neck cancers, metastatic bladder cancer, certain types of lung cancer and a few other malignancies and has shown effectiveness with many mesothelioma patients. Fatigue and Cough are the most common Keytruda side effects. Keytruda cost for a treatment period is about £84,000 per patient.
Keytruda during time
IN 2006, Medical Research Council Technology (now known as LifeArc) started to humanize the antibody and at the end of this research, scientists Gregory Carven, Hans van Eenennaam, and John Dulos invented Pembrolizumab.
In 2010, the development has been finished and Merck began preparing to out-license it.
In 2011, The phase I of the study started in early 2011, and around 1300 people participated in the trial; it was the largest Phase I study ever run in oncology with the patients roughly divided between melanoma and lung cancer.
In 2013, the name of the drug changed from Lambrolizumab to Pembrolizumab.
In 2014, Pembrolizumab was approved by the FDA for use in treatment with Ipilimumab, or after treatment with Ipilimumab and a BRAF inhibitor in advanced melanoma patients who carry a BRAF mutation.
In July 2015, it received marketing approval in Europe.
In 2016, it received marketing approval in Japan and signed a co-promoting agreement with Taiho Pharmaceutical.
In 2015, It was approved by the FDA for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents
In July 2016, the US FDA approved Pembrolizumab as a treatment for patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.
In May 2017:
- It was approved by chemotherapy as a first-line treatment for metastatic non-small cell lung cancer (NSCLC).
- FDA Approved Merck’s Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer Whose Tumors Express PD-L1
In June 2018, the FDA approved Pembrolizumab for treatment of advanced cervical cancer for PD-L1 positive patients and also for patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).
Pembrolizumab is the first approved cancer drug by the FDA based on tumor genetics rather than tissue type or tumor site. KEYTRUDA, a programmed death receptor-1 (PD-1)-blocking antibody, is used to treat
- Unresectable or metastatic melanoma
- Metastatic non-small cell lung cancer (NSCLC)
- Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
- Refractory classical Hodgkin Lymphoma (CHL)
- Locally advanced or metastatic Urothelial Carcinoma
- Primary mediastinal B-cell lymphoma (PMBCL).
- Gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Cervical cancer
Keytruda side effects
As the Common Keytruda side effects we can name
- shortness of breath,
- loss of skin pigmentation (vitiligo),
- decreased appetite,
Pembrolizumab is classified as a monoclonal antibody that is a relatively new type of “targeted” cancer therapy. It binds to the PD-1 ( programmed cell death protein 1 located on lymphocytes) receptor and deactivated it so that its interaction with the ligands, PD-L1 and PD-L2 will be blocked. As a result of this binding, T-cell–mediated immune responses will be activated against tumor cells. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.
Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to the inhibition of active T-cell immune surveillance of tumors.
The function of this receptor is to prevent the immune system from attacking the body’s own tissues; it is a so-called immune checkpoint. Most cancers make proteins that bind to PD-1 and shut down the ability of the body to kill the cancer cells. Blocking PD-1 allow the immune system to target and destroy cancer cells. The same mechanism allows the immune system to attack the body itself; Pembrolizumab is a type of checkpoint inhibitors with immune-dysfunction side effects.
- Normal immune response
When functioning properly, T cells are activated and can attack tumor cells.
- Tumor ivasion and T-cell deactivation
Some tumors can evade the immune system through the PD-1 pathway. The PD‑L1 and PD‑L2 ligands on tumors can bind with PD-1 receptors on T cells to inactivate the T cells.
- T-cell reactivation with Keytruda
Keytruda binds to the PD-1 receptor and blocks its interaction with PD‑L1 and PD‑L2, which helps restore the immune response. While having an effect on the tumor, this could also affect normal healthy cells.
Keytrudain the Market
It is expected that the market size of cancer immunotherapies grows more than fourfold from $16.9 billion in 2015 to $75.8 billion by 2022 and representing a rapid compound annual growth rate (CAGR) of 23.9%. So that Keytruda exporters and also Turkish pharmaceutical sellers will witness a significant growth in this market in the near future.
Established immunotherapies, particularly Revlimid, Opdivo, Keytruda, and Gazyva, will show rapid sales growth throughout the forecast period, with Keytruda and Opdivo rising by $7 billion and $9 billion, respectively.
It is anticipated that the global immune checkpoint inhibitors market cross US$ 25 Billion by 2022. The global immune checkpoint inhibitors market has been divided into PD-1, PD-L1, and CTLA-4 on the basis of the type of product. It is estimated that PD-1 be the largest share in 2016. On the basis of the type of cancer, Lung Cancer & Melanoma will be the nominated type in the market.
In the following figure, Sales forecast will be shown in the seven major markets (United States, France, Germany, Italy, Spain, the United Kingdom, and Japan) from 2013 to 2020.
Figure 1: Major-market sales of select immune checkpoint inhibitors (estimated).
Dano Health as a clinical trial product distributor can provide Keytruda for the companies who are looking for it.