The immuno-oncology (IO) field has a lot to be thankful for as the year comes to a close.
Not only are PD-1/PDL-1 inhibitors being rapidly approved, their use is being extended into new indications and tumor types well beyond what people expected. From melanoma and lung cancer to bladder, gastric and liver cancer, drugs like Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo are finding new markets. The results of long-range studies that are beginning to emerge indicate improvements in long-term survival among those who were first treated with these drugs. CAR-T therapy and other “next-generation” IO treatments, such as those targeting the LAG-3 protein, as reported earlier this year at ESMO, as well as vaccines, viruses, and neoantigens, are also generating excitement.
In a recent Mendelspod podcast, we – Bionest partners Rachel Laing and Olivier Lesueur – joined host Theral Timpson to discuss the incredible strides made in the IO field this year, and to consult our crystal balls for a glimpse into what to expect in 2018.
One of the big paradigm shifts has been in biomarkers. As we pointed out in a 2016 publication, gone are the days of straight-forward companion diagnostics, when biomarkers were simply read-outs of targets, paired directly with a drug. Several biomarkers are now being used to identify patients who might respond to drugs that are already on the market, and to support further U.S. Food and Drug Administration approvals for drugs based on those biomarkers.
Biomarkers are and will be more complex within immuno-oncology. One of the reasons for that is the complexity of the immune system. We’re not just dealing with the tumor cells and the signaling that goes on in the tumor cells; there’s a lot of interplay between the tumor, the microenvironment, and the immune system. We’re relying on a drug to activate the immune system and to target the tumors, and therefore it’s unrealistic to think that we can get away with measuring just one biomarker.
While IO has been a fantastic advance in the field of cancer therapeutics, we are likely to end up with a situation where some people will be treated very well by a single agent therapy, while other patients will need IO plus another targeted therapy, or the IO drug plus a chemotherapy. That’s where the next challenge lies – how to integrate all these tools and do it in a smart way.
Money is also a big issue. The investment required to become a player in the IO field is astronomical, and may be a limiting factor for many companies. CAR-T therapy, for example, requires a large up-front investment to ensure that the complex manufacturing process is ready at an early stage, well before commercialization. This means a lot of investment must be made early in the development process. As a result, it really remains to be seen how many companies will be able to enter this field, and what this means for competitiveness and the development of new CAR-T products and players in the market.
Then there’s the pricing issue. With estimates as high as $475,000 per CAR-T treatment, the hefty price tag is definitely an issue the industry is exploring. Another issue, however, is how to cover the cost of developing the biomarkers that are proving to be so vital to the future success of the IO field. Biomarker tests are expensive and not always reimbursable. If reimbursable, at what point in the disease progression does a patient qualify? By the time the payer says yes, it might be too late to detect some of the markers as tumors continue to change over time.
As we predicted back in 2014, we may be approaching an era of diagnostics leadership, where pharmaceutical companies end up footing some of the bill for diagnostic development and testing.
Because diagnostics are becoming so important as a means of telling which drug will work when, for what patient, and/or in what combination within a treatment regimen, we might see the situation where value shifts from the pharmaceutical industry to the diagnostic companies. Any serious pharmaceutical player today has to have a biomarker or diagnostic partnering strategy in place very early on.
We worry that all the cost and complexities of these treatments may limit access, and that more attention should be paid to the patient experience.
As for our predictions for 2018? Listen to the podcast to find out.