Checkpoint Inhibitors: Global Markets

Executive Summary

The treatment of cancer patients involves a multidisciplinary approach encompassing surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination cytotoxic chemotherapy or targeted agents; although chemotherapy treatment has good response rates complete responses are rarely seen. During the last decade the field of immuno-oncology has rapidly advanced and a number of agents which modulate the immune system are beginning to emerge and change treatment paradigms. Two of the most prominent and promising class of drugs are the immune checkpoint inhibitors, that target the proteins found on T-lymphocytes or T cells such as programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways.

The immune checkpoint inhibitors are causing a stir amongst oncologist as they have been shown to be effective in the treatment of a variety of cancers, enhancing the immune response to detect and target cancer cells with a lower incidence of side effects compared to conventional chemotherapy and providing durable responses, lasting for many years. Five checkpoint inhibitors have received rapid approval from the U.S. Food and Drug Administration for cancer, including the PD-1 inhibitors Keytruda (pembrolizumab), and Opdivo (nivolumab), the PD-L1 inhibitors Tecentriq (atezoliumab), Bavencio (avelumab) and Imfinzi (durvalumab) and the CTLA-4 inhibitor Yervoy (ipilimumab). In 2011, Bristol Myers Squibb’s Yervoy a CTLA-4 inhibitor became one of the first checkpoint inhibitors to be approved in the treatment of metastatic melanoma, despite considerable safety and tolerability concerns. It took a further 3 years before the next checkpoint inhibitor Keytruda, a PD-1 inhibitor was approved for the treatment of advanced unresectable melanoma.

According to clincailtrial.org, there are more than 230 clinical trials underway evaluating checkpoint inhibitors either as a monotherapy or in combination with chemotherapy or targeted therapies these encompass a wide variety of caner sub-types: including 117 Phase 1 trial, 112 Phase 2 trial and 9 Phase 3 studies. Several novel agents are in early-stage clinical development that target novel pathways including the T cell immunoglobulin and mucin containing protein 3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3) protein inhibitors, CD-47/signal regulatory protein a (SIRPa) and immunometabolic enzymes Indoleamine 2,3 dioxygenase-1 (IDO-1) which utilize an array of innovative delivery technologies such as small molecule agents, monoclonal antibodies, bispecific antibodies and fusion proteins to target inhibit checkpoint proteins.

Novel classes if checkpoint inhibitors will enter the market, companies will identify clinically effective combinations and validate biomarkers and signatures that will enable them to help identify patients that are most likely to benefit from treatment. Personalized precision medicine will be a major driver for pharma to effectively deliver these innovative medicines and ensure they are accessible and available at sustainable prices to all those in need.

Companies Mentioned

• Agenus Inc.
  
• ALX Oncology
  
• Anaptys Bio
  
• Beigene
  
• Biocad
  
• Crescendo Biologics Ltd.
  
• Cstone Pharmaceuticals
  
• F-Star Biotechnology
  
• Forty Seven, Inc.
  
• Immutep, Ltd.
  
• Inhibrx
  
• Macrogenics, Inc.
  
• OSE Immunotherapeutic
  
• Regeneron Pharmaceuticals, Inc.
  
• Seattle Genetics, Inc.
  
• Shanghai Cell Therapy
  
• Sorrento Therapeutics, Inc.
  
• Surface Oncology
  
• Symphogen A/S
  
• Tesaro, Inc.
  
• Trillium Therapeutics
  
• Xencor