Cancer immunotherapy continues to revolutionize oncology drug development, generating huge interest from biopharma companies, academia and investors alike. Last year, we charted the development and deal activity specifically for one of the most prominent classes of immunotherapies—immune checkpoint inhibitors—and here we return to update the graphic, to reflect the rapid progression of the market, including the approval of two new drugs.

These drugs work by inhibiting immune checkpoint proteins that regulate the activity of T cells, thereby ‘releasing the brakes’ on T cells to enable them to attack cancer cells. So far, inhibitors have been successfully developed for cytotoxic T lymphocyte– associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) (Fig. 1). The first checkpoint inhibitor, Yervoy (ipilimumab), developed by Bristol-Myers Squibb, was approved for unresectable or metastatic melanoma in March 2011. Since then, five additional checkpoint inhibitors—the PD1 inhibitors Opdivo (nivolumab) and Keytruda (pembrolizumab), and the PDL1 inhibitors Tecentriq (atezolizumab), Imfinzi (durvalumab) and Bavencio (avelumab)— have been approved (Fig. 2).

With the aim of maximizing the success and impact of this first wave of checkpoint inhibitors, companies have initiated a large number of trials to combine checkpoint inhibitors with each other and with other cancer immunotherapies, as well as with drugs in different classes such as epigenetic modulators and kinase inhibitors. In September 2015, Bristol-Myers Squibb received the first combination-regimen US Food and Drug Administration (FDA) approval for Opdivo (nivolumab) + Yervoy (ipilimumab) in BRAF V600 wild-type melanoma. According to data in a report—published in May of this year, from EvaluatePharma on PD1/PDL1 combination therapies—in 2015 approximately 200 trials involving PD1 and PDL1 assets were being conducted. Now, over 700 studies are being conducted, and the majority of these involve Keytruda. In Table 1, we highlight some of these combination trial deals and we present the number of overall active deals in Figure 3.

Figure 1: The names and approval status of currently approved and selected late-stage checkpoint inhibitors. Color-coded according to their target. CTLA4, cytotoxic T lymphocyte-associated antigen 4; FDA, US Food and Drug Administration; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small-cell lung cancer; PD1, programmed cell death protein 1; PDL1, programmed cell death 1 ligand 1; RCC, renal cell carcinoma. *Known as MSD outside the United States and Canada.

Figure 2: A timeline of selected approvals and collaborations for checkpoint inhibitors. BMS, Bristol-Myers Squibb; CAR, chimeric antigen receptor; dMMR, mismatch repair deficient; FDA, US Food and Drug Administration; GSK, GlaxoSmithKline; HL, Hodgkin lymphoma; mAb, monoclonal antibody; MSH, microsatellite instability-high; nab, nanoparticle-albumin-bound; NHL, non-Hodgkin lymphoma; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma. *Known as MSD outside the United States and Canada.

Figure 3 (left): Number of active deals to date involving approved checkpoint inhibitors. Source, Clarivate Analytics. Figure 4 (right): Current and forecasted sales of approved checkpoint inhibitors. Source, Clarivate Analytics.

As a major focus in oncology, the largest therapeutic area globally in terms of market value and R&D spending, immuno-oncology assets are valued extremely highly and have already brought in large profits. Predictions have been made that the market could be worth up to $100 billion by 2025 ( Nat. Rev. Drug Discov . 16, 83–84, 2017). We reviewed existing sales data for all the current approved checkpoint inhibitors with forecasted data to provide an overview of what this segment of the immuno-oncology market could eventually be worth. The first two PD1 inhibitors to enter the market, pembrolizumab and nivolumab, have the highest forecasted sales (Fig. 4), which are predicted to peak at more than $10 billion annually.

Table 1: Selected combination-trial deals involving checkpoint inhibitors in 2017

Month (2017)

Primary Company

Partner Company

Checkpoint inhibitor

Deal summary

Feburary

Merck & Co.*

Boehringer Ingelheim

Pembrolizumab

Collaboration to evaluate Gilotrif (afatinib) with pembrolizumab for patients with squamous cell carcinoma of the lung in phase 2 trial.

March

Roche

Bavarian Nordic

Atezolizumab

Bavarian Nordic collaborates to evaluate its cancer vaccine CV301 with atezolizumab for bladder cancer.

March

Merck & Co.*

BerGenBio ASA

Pembrolizumab

BerGenBio partners with MSD to evaluate its AXL kinase inhibitor BGB324 in combination with pembrolizumab in advanced lung and breast cancer.

May

BMS

Advaxis

Nivolumab

Collaboration to evaluate nivolumab with Advaxis’s ADXSDUAL, an immunotherapy targeting HPV-associated cancers, for the treatment of women with metastatic cervical cancer.

May

Pfizer and Merck KGaA

EpiThany

Avelumab

Collaboration to evaluate avelumab with EP-101 STEMVAC, a multi-antigen, polyepitope vaccine, in a phase 2 trial in women with breast cancer.

May

Merck & Co.*

Array BioPharma Inc.

Pembrolizumab

Partnership with Merck to investigate Array’s MEK inhibitor binimetinib, with pembrolizumab, in metastatic colorectal cancer patients with microsatellite stable tumors.

June

Pfizer and Merck KGaA

eFFECTOR Therapeutics

Avelumab

eFFECTOR Therapeutics to collaborate with Pfizer and Merck KGaA to evaluate eFFECTOR’s MNK1/2 inhibitor eFT508, in combination with avelumab in patients with microsatellitestable relapsed or refractory CRC.

June

National Cancer Institute, AstraZeneca

Eleven Biotherapeutics

Durvalumab

Evaluation of activity of Eleven’s fusion protein Vicinium(VB4-845) in combination with durvalumab for NMIBC

June

Genentech (Roche)

Inovio Pharmaceuticals

Atezolizumab

Inovio Pharmaceuticals partners to trial its T cell activator INO-5401 with Genentech’s atezolizumab for advanced bladder cancer.