Source: National Cancer Institute.
There is arguably no indication that offers a faster long-term growth rate for drug developers than oncology -- and rightly so with very few cancers being well understood by researchers, and most still proving deadly.
Within cancer care research there are multiple pathways drug developers can take to fight cancer. Traditional chemotherapy products attack cells throughout the body (both healthy and cancerous cells), while another class of cancer-fighting drugs may focus on inhibiting angiogenesis, or the formation of new blood vessels. Without new blood vessels parts of a fast growing tumor can starve, leading to cancer cell death.
Cancer immunotherapies: the cream of the crop
However, the cream of the crop at the moment in cancer care research is cancer immunotherapies. These are therapies designed to enhance your immune system to more efficiently locate and/or destroy cancer cells. Cancer has a way of going undetected by the body's immune system, thus allowing it to proliferate. Newly approved immunotherapies, such as Keytruda and Opdivo, are checkpoint inhibitors that alert the immune system to a "foreign" cell to elicit an immune response.
Source: Bristol-Myers Squibb.
Early results from Keytruda, Opdivo, and other cancer immunotherapies have been encouraging. Although the patient pool can sometimes be dependent on whether or not a specific protein, PD-1 or PD-L1, is present or not (its presence can have a substantial impact on response rate depending upon the type of cancer), response rates in non-small cell lung cancer for select patient subsets were incredibly high given that the patients tested with both Keytruda and Opdivo had progressed on previous therapies. Not surprisingly, Keytruda and Opdivo are both approved to treat non-small cell lung cancer and BRAF V600 mutation-positive metastatic melanoma.
Cancer immunotherapies have a decent shot at shaping the future of personalized cancer treatment for the next decade and beyond. However, Wall Street, investors, and consumers on the outside looking in are overlooking the unsung heroes behind the success of the cancer immunotherapy and personalized medicine effort: the diagnostic test developers.
Diagnostic test developers are changing the game
Diagnostic tests developers are responsible for crafting the tests capable of determining which patients would be best suited for a specific immunotherapy. As noted above, some therapies work best when PD-1 or PD-L1 expression is high in patients, making those patients potentially best suited to receive one of the newly approved immunotherapies.
With this in mind, let's have a brief look at a few of these behind the scenes heroes that are changing the face of cancer treatment and diagnosis.
Source: National Cancer Institute.
Quest Diagnostics (DGX 5.08%)
Following the approval of Merck's (MRK -0.05%) Keytruda by the Food and Drug Administration as a treatment for metastatic NSCLC earlier this month, Quest announced that it'd be providing testing services for the PD-L1 1HC 22C3 PharmDx companion diagnostic test developed by Dako to physicians and consumers throughout the United States.
The test, as its namesake implies, will qualify whether patients are expressing high levels of PD-L1, a programmed-death ligand that can interact with the PD-1 protein and provide an immunosuppressant quality to cancer cells. Keytruda inhibits this interaction, allowing the immune system to discover and destroy cancer cells. In Keytruda's phase 1b metastatic NSCLC study known as KEYNOTE-001, the overall response rate in patients with less than 50% PD-L1 expression was just 16.5%. For those with 50% or higher levels of PD-L1 expression, the response rate jumped to an impressive 45.2%.
Quest is also responsible for a number of other cancer-based diagnostic tests, helping physicians identify mutations in the EGFR, KRAS, and ALK genes. Identifying patients with these mutations allows for FDA-approved cancer treatments that can improve patient quality of life and potentially extend survival.
Agilent Technologies (A 3.95%) & Ono Pharmaceutical
On the other side of the coin we have Agilent Technologies, via its subsidiary Dako, in partnership with Ono Pharmaceutical developing a companion diagnostic test specifically for use with Bristol-Myers Squibb's (BMY -0.30%) Opdivo for the treatment of NSCLC.
Source: Agilent Technologies.
In similar fashion to Keytruda, Opdivo's results in CheckMate-057, a phase 3 open-label randomized study, demonstrated impressive response rates for patients expressing high levels of PD-L1. The risk of death was reduced by 60% for patients with high PD-L1 expression, and 27% overall for the 582 previously treated patients in the study. Dako and Ono's diagnostic contribution could be critical to ensuring that the right NSCLC patients are getting Opdivo, and that they're getting the three-month improvement in overall survival that was demonstrated over the docetaxel chemotherapy arm in clinical studies.
Roche (RHHBY 1.07%)
Sometimes the cancer immunotherapy developer is also the designer behind a companion diagnostic test. This is the case with Roche and Roche Diagnostics, which is also working on a diagnostic device to measure PD-L1 levels in patients who may be best suited for Roche's experimental immunotherapy drug atezolizumab.
Source: Roche.
Two recently reported phase 2 studies involving atezolizumab demonstrate the promise of the anti-PDL1 therapy. In metastatic urothelial carcinoma (advanced bladder cancer) atezolizumab led to an objective response rate of 27%. The exact same ORR of 27% was generated in the BIRCH metastatic NSCLC study. However, the improved overall survival of 7.7 months over the control group for NSCLC patients expressing high levels of PD-L1 is incredible, and it demonstrates fully how powerful these companion diagnostics can be when drug developers get the right drugs to the right patients.
To be clear, we're liable to see more diagnostic test developers enter the fray as immunotherapies grow in popularity and effectiveness. As both someone who's genuinely interested in seeing cancer eradicated, and in investing in game-changing companies, I'd be sure to add some or all of these names to your watchlist as they're liable to play a big role in cancer care research and treatment in the coming years.
