CHICAGO — Drugs which enlist the body's immune system have become important tools in the fight against many tumors. The way doctors treat advanced lung cancer, for instance, has changed substantially in the less than five years since Merck & Co.'s Keytruda and Bristol-Myers Squibb's Opdivo came to market.
Money poured into immuno-oncology research over that period, and the number of regulatory approvals jumped. Four more drugs that work like Keytruda and Opdivo have become available, including Pfizer and Merck KGaA's Bavencio (avelumab).
Bavencio sales remain far behind those of other PD-1 and PD-L1 checkpoint inhibitors, though they may begin to inch up as the drug moves into more diseases.
Last month, regulators cleared it in combination with another Pfizer drug, Inlyta (axitinib), as a first-line treatment for advanced kidney cancer. Pfizer is also testing Bavencio across a range of other cancers — an effort that contributed to a 4% increase in R&D spending in 2018.
While Pfizer lags in immunotherapy, the pharma has enjoyed a recent steak of successes with targeted cancer therapies. Last fall, in the span of about two months, four targeted drugs from Pfizer won approval in the U.S. across both blood and solid cancers.
Rival cancer drugmakers, however, also see promise in the targeted approach, as evidenced by clinical data from Novartis, Amgen and Roche at the American Society of Clinical Oncology's meeting this weekend.
Chris Boshoff, chief development officer for Pfizer Oncology, spoke with BioPharma Dive to discuss Pfizer's ambitions in oncology and how approaches outside of immunotherapy will contribute.
This interview has been lightly edited and condensed for clarity.
BIOPHARMA DIVE: Immunotherapy is, especially at this year's ASCO, sharing the spotlight with targeted cancer treatments. Is this something we can expect at future oncology meetings?
BOSHOFF: Probably even more so. That's a big part of our strategy at Pfizer oncology. We're not just focused on immunotherapies, we've got a very diverse portfolio with a big emphasis on targeted therapies.
We're really thinking the future of cancer medicine is this combination of medicines, whether it's targeted therapies or antibody-drug conjugates or antibodies.
But it's combinations with targeted therapies that's going to continue to be very dominant.
Is it fair to assume, then, that your pipeline of targeted cancer therapies will grow larger?
BOSHOFF: Definitely. If you look at our current medicines in Phase 1, most of those are targeted therapies. Although, we also do have some immunotherapies and novel medicines like ADCs [and bispecifics].
We are now looking at those drugs or those targets that have been difficult in the past to make targeted therapies against. Perhaps a good example of that is our CDK 2/4/6, which was difficult before to do but is now doable.
What guides your R&D investments in targeted cancer therapies? Do you get inspiration from biotechs, or do most of the decisions that Pfizer makes stem from in-house developments?
BOSHOFF: A big part of it is internal, and a big strategy is to enhance our current medicines.
We have Ibrance, which is an important medicine in ER-positive, HER2-negative breast cancer. So how else do we expand in the space of breast cancer? How else do we expand in tumors that become resistant to Ibrance?
We did work in collaboration with international cancer researchers and discovered that one of the mechanisms is cyclin E amplification.
How can you overcome that? You have to target CDK 2. That's why we then internally, with our medicinal chemists, developed a new drug targeting CDK 2/4/6.
Will a wide arsenal of potential combinations be necessary to stay relevant in the cancer therapy space?
BOSHOFF: It's important to have a very diverse portfolio. That helps you to optimize combinations. That helped us certainly with Inlyta and having a PD-L1.
Having a good backbone [is also important]. So take prostate cancer: a next-generation androgen inhibitor like enzalutimide helps us because that's a very good backbone to build upon.
But we do certainly also look externally; what would be external medicines to combine it with, whether it's from either large pharma or from biotech.
No matter how big you are, no one has all the best medicines to combine with. So if there's a medicine that we believe is a very good partner for one of our drugs and it's external, then we'll see how we can partner.
When Bavencio came to market a handful of checkpoint inhibitors were already there. What lessons or strategies did you learn from that launch?
BOSHOFF: There's a number of other opportunities with Bavencio that we will optimize, although we've recognized that we haven't invested as much in Bavencio as others have in their immune checkpoint blockers — partly because Pfizer is a diverse company, we're not focused just in oncology.
We've got five therapeutic areas, although oncology is getting a very good chunk of our R&D investment.
Also within oncology we are diverse. We are not just going to focus on immune checkpoint blockers because we recognize that the future of cancer medicine is combinations and a holistic approach, a systems approach.
[That recognition led us to believe] we do need an optimal immune checkpoint blockade as a backbone for some of our future combinations. So we have developed internally also an anti-PD1 that's currently in Phase 1.
Why are we developing another checkpoint? The current checkpoints are essentially all being developed as intravenous infusion. This one is being developed specifically only as a subcutaneous administration, so it will be a prefilled syringe. The current regimen is once every four weeks, but our [pharmacokinetic] data indicates we potentially can go once every six weeks.
Having a subcutaneous, prefilled syringe as a backbone to targeted therapies we feel could optimize the way we develop immune checkpoints in the future.
Is there a first-mover advantage with targeted cancer therapies and, if so, how might they compare to the checkpoint inhibitor space?
BOSHOFF: Having a first in class can often help. That has certainly helped us with Ibrance.
Does that mean there's not a place for future CDK 4s or CDK 2/4/6s? No. So that's why we are also internally developing the next generation cell cyclin inhibitor.
I think especially if you want to move to earlier lines of treatment — for example the adjuvant setting — then even if you're slightly later, but you've got a best-in-class medicine, that can be an advantage.
Resistance is another area that's very important for us. Lorlatinib is a very good example. That was developed as a follow-up medicine to Xalkori in ALK-positive lung cancer.
With Xalkori, up to 50% of patients actually develop brain metastases. Lorlatinib crosses the blood-brain barrier and in preclinical data indicates it overcomes all the resistant mutations to Xalkori. So we considered that not as a first-in-class, but a potentially best-in-class medicine.