PD1/PD-L1 Inhibitors Market: Competitive Landscape, Pipeline, and Market Analysis 2023

PD1/PD-L1 Inhibitors, also known as Programmed Cell Death Protein 1 Inhibitor, are immunotherapy that blocks the PD-1 receptor in immune cells. PD-1 is a checkpoint protein that helps regulate the immune response and prevent pathways to evoke detection and destruction by the immune system. PD-1 is an inhibitor of adaptive and innate immune responses and is expressed on activated T lymphocytes, natural killer (NK) lymphocytes, B lymphocytes, macrophages, dendritic cells (DC), and monocytes. Notably, PD-1 is highly expressed in tumor-specific T cells. PD-L1 is normally expressed by macrophages, some activated T and B cells, DCs, and some epithelial cells, especially under inflammatory conditions. In addition, PD-L1 is expressed by tumor cells as an 'adaptive immune mechanism' to evade anti-tumor responses. PD-1 inhibitors block the interaction of PD-1 with PD-L2 ligands on cancer cells preventing the cells from sending inhibitory signals to the immune cells, allowing them to recognize and attack the cancer cells. The activity of PD-1 and its ligands PD-L1 or PD-L2 is involved in T cell activation, proliferation, and cytotoxic secretion in cancer and alters anti-tumor immune responses. These have shown significant clinical efficacy in various cancers, including melanoma, lung cancer, kidney cancer, bladder cancer, and Hodgekin’s Lymphoma. The 1^st PD-1  Inhibitor approved was Keytruda (pembrolizumab) in 2014. Following that, many new molecules have been evaluated in clinical trials and got FDA approvals. Extensive research is being conducted globally to discover new and novel molecules to be used, like pembrolizumab, which is used to treat many indications like Non-small Cell Lung Cancer. The development and launch of new products will thus increase the market’s revenue in the forecasted years.

Several of these inhibitors are on the market, while many are in ongoing clinical trials. Various companies have various products in their pipelines, with 147 products in multiple stages of clinical trials – 9 in Phase 4, 43 in Phase 3, 82 in Phase 2, and 83 in Phase 1 of the clinical trials.

Key developments of PD1/PD-L1 Inhibitors

• In April 2023, FDA approved Keytruda (pembrolizumab) in combination with Padcev (enfortumb vedotin-ejfv) for 1^st line treatment of patients with Locally Advanced or Metastatic Urothelial Cancer.
• In March 2023, FDA converted to full approval indication for Keytruda (pembrolizumab) for certain adult and pediatric patients with Advanced Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors.
• In January 2023, FDA approved Keytruda as an adjuvant treatment following surgical resection and Platinum-Based chemotherapy for patients with Stage 1B, II, or IIIA Non-small Cell Lung Cancer.
• In May 2022, FDA approved 2 Opdivo (nivolumab) based regimens as 1st line treatments for Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma.
• In May 2022, FDA approved Opdivo (nivolumab) with chemotherapy as neoadjuvant treatment for adult patients with Resectable Non-Small Cell Lung Cancer.

Approved PD1/PD-L1 Inhibitors molecules

• Keytruda (pembrolizumab)
• Opdivo (nivolumab)
• Tecentriq (atezolizumab)
• Imfinzi (durvalumab)
• Baizean (tislelizumab)
• AiRuiKa (camrelizumab)
• Tuoyi (toripalimab)
• Tyvyt (sintilimab)
• Bavencio (avelumab)
• Libtayo (cemiplimab)
• Kaitanni (cadonilimab)
• Jemperli (dostarlimab-gxly)
• spartalizumab (PDR001)
• Anniko (penpulimab)

Drugs in the Pipeline of PD1/PD-L1 Inhibitors

• bintrafusp alfa (M7824)
• Hansizhuang (serplulimab)
• Enweida (envafolimab)
• Zynyz (retifanlimab-dlwr)
• zimberelimab (AB122)
• APL-502
• adebrelimab (SHR-1316)
• retlirafusp alfa (SHR-1701)
• balstilimab (AGEN2034)
• ezabenlimab (BI 754091)
• erfonrilimab (KN046)
• ivonescimab (AK112)
• Puyouheng (pucotenlimab)
• budigalimab (ABBV-181)
• Opdualag (nivolumab/relatlimab) and many more

Clinical Activity and Developments of PD1/PD-L1 Inhibitors
As of July 2023, various companies have approximately 147 products for 317 diseases. For these diseases, many trials are being conducted by players globally. For instance,

• Samsung Medical Center is conducting a Phase 4 clinical trial to assess Pembrolizumab for Metastatic Non-small Cell Lung Cancer (NSCLC) patients expressing PD-L1 who have their own Patient-derived Xenograft (PDX): a comparative study of clinical response and in-vivo antitumor response using their Humanized CD34 PDX (Hu-CD34 PDX) that is expected to complete by August 2023.
• Merck Sharp and Dohme LLC are conducting a Phase 4 clinical trial to evaluate the efficacy and safety of Pembrolizumab (MK-3475) plus Carboplatin and Paclitaxel as first-line treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE B10) that is expected to complete by July 2024.
• Henan Cancer Hospital is conducting a Phase 4 clinical trial to explore low-dose Gemcitabine combined with Nivolumab for 2^nd line and higher line treatment of Driving-Gene Negative Non-small Cell Lung Cancer that was expected to complete by April 2023.