The 2010s closed with another strong year for oncology drug approvals. This included new treatments for people with prostate, bladder, breast and lung cancer receiving approval from the United States Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER). Among those that got the green light, immunotherapy drugs held the majority. The FDA also approved 10 new biosimilars, adding another dimension to competition and pricing.
As the global cancer burden continues to climb — 18.1 million new cases in 2018 according to World Health Organization — scientists continue to develop new ways to treat and beat the disease. Immunotherapy has gained worldwide acceptance for its generally lower side effects, ability to enhance benefits of chemotherapy and radiation and its ability to work when chemo and radiation don’t. Drug developers are taking big risks through R&D, acquisitions and partnerships in order to deliver patients the best treatments.
Pembrolizumab (Keytruda), a PD-1 inhibitor manufactured by Merck & Co., holds a strong lead among top immunotherapy drugs on the market. Keytruda treats melanoma, classic Hodgkin lymphoma, and metastatic non-small cell lung cancer, among other cancers.
Keytruda alone generated $11.1 billion in sales for Merck in 2019. With about 1,000 reported active clinical trials currently looking at Keytruda, combined with Merck’s R&D muscle, EvaluatePharma projects the drug to double worldwide sales by 2024, provided it maintains its strong historical year-over-year increase.
Among the PD-L1 inhibitors, Roche’s Tecentriq and AstraZeneca’s Imfinzi are nearly neck and neck in 2019 worldwide sales. However, AstraZeneca estimates about $2 billion less in R&D costs, so it may reap higher profits. In its Fiscal Year 2018 report, the company notes it doubled its oncology sales overall that year with support from Imfinzi.
While PD-1/PD-L1 inhibitors and T-cell stimulants ranked highest among the most profitable mechanisms of action, CTLA antibodies placed a strong fourth in the immunotherapy MOA race. CAR T-cell therapies had the strongest projected sales by 2024; however, CTLA antibodies showed stronger sales in 2019 and a much higher rate of approval: 80% in phase 3 compared to 33%.
Although CTLA antibodies have shown high toxicity in clinical trials, their results treating late-stage melanoma keep researchers pressing forward.
The strongest-performing immunotherapies on the market are the programmed cell death protein 1 (PD-1) checkpoint inhibitors, according to EvaluatePharma sales data. PD-1 checkpoint proteins live on the surface of immune cells called T cells. PD-L1 proteins (another checkpoint protein) bind to PD-1 and prevent T cells from attacking tumor cells. Drugs that target PD-1 boost immune response against cancer cells and prevent PD-L1 proteins from binding and protecting PD-1s.
Drugs using this mechanism of action (MOA) saw nearly $19.4 billion in worldwide sales in 2019. According to EvaluatePharma consensus sales forecasts, the total global PD-1 market will be worth over $36 billion by 2024. Strong approval history — 97% of Phase III products went on to receive FDA approval — supports these projections. Advances in therapies that combine PD-1 inhibitors with chemotherapy, radiation and CTLA-4 blockade, another immune checkpoint inhibitor, contribute to its projected growth.
How is the PD-L1 forecast growing?
No surprise PD-L1 checkpoint inhibitors rank second in worldwide sales based on MOA. PD-L1 checkpoint inhibitors prevent PD-L1 from doing its job, which allows T cells to kill cancer cells. To date, FDA has approved three PD-L1 inhibitors: Atezolizumab (Tecentriq), Durvalumab (Imfinzi), and Avelumab (Bavencio). Others are in development.
With $3.43 billion in sales in 2019, the PD-L1 inhibitor market is projected to grow to $10.5 billion by 2024. Considering immunotherapies with this MOA soared from $159 million to $1.47 billion from 2016 to 2018, combined with pharma’s assertive investment in checkpoint inhibitors generally, that’s a sound projection.
Of immunotherapies that use an adoptive cell transfer approach, CAR T-cell therapy brings together the body’s natural T cells with a modified version.
CAR T-cell therapy involves collecting a patient’s T cells, modifying them to produce special cancer-killing antigens, and reinfusing them into the patient. The CAR T cells then release cytokines and other soluble mediators that may directly kill both cancer cells and normal cells.
FDA approved CAR-T therapies
So far the FDA has approved two CAR T-cell therapies — Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) — for adults living with certain types of non-Hodgkin lymphoma and for people under age 25 living with acute lymphoblastic leukemia that has relapsed. They will have company soon. Bristol-Myers Squibb, Autolus Therapeutics and a host of other companies have CAR T-cell therapies in development for other types of blood cancer.
EvaluatePharma project the market for T-cell stimulant drugs, which includes primarily CAR T-cell therapy products, to nearly triple from 2019 to 2021 — from $740 million to $2.1 billion in worldwide sales. CAR T-cell therapies are challenging to develop, and they’ve had their share of setbacks over the years. The approval of Yescarta and Kymriah has built confidence for this group as researchers explore additional improvements in technology and manufacturability.