Are drugmakers spending too much money developing new medicines for cancer? In a world where the amorphous disease remains one of the deadliest afflictions, it's a strange question to ask.
Yet surging investment into the red-hot field of immuno-oncology has spurred concerns of duplicative research and wasted effort chasing "me-too" drugs.
On Wednesday, more than a hundred executives, researchers and investors filled an auditorium in the Cambridge headquarters of Sanofi SA's Genzyme division to consider, among other topics, whether the industry has overcommitted itself to cancer.
The answer, it seems, is one of perspective. When considering the industry as a whole, venture capitalists and executives from top pharma companies agreed research seems over-concentrated in certain areas. But when asked if that changed their willingness to make bets on new companies and promising drugs, all remained eager to invest.
"As long as we can be led to believe that you can start to use words like cure in a much larger fraction of the population than we can even come close to doing today, the justification is there," explained Robert Urban, global head of Johnson & Johnson Innovation, in comments to the assembled group at the Boston Cancer Summit.
Piling into cancer research
Several factors combine to make oncology a particularly attractive area of therapeutic research.
Most cancers remain uncurable, making the need for more effective drugs particularly acute. At the same time, a growing understanding of cancer biology at a molecular level has enabled better targeting of treatment as well as more sharply defined patient populations.
Add in an accommodative regulator and biopharma companies see opportunity to quickly reach patients with drugs that can command steep prices.
That mix has led most pharmas to tap oncology as a core focus and has sparked increased investment by venture firms into cancer-focused biotechs.
"Oncology is not one market. It is lots of markets. Parts of it are incredibly crowded and over-invested," explained John Evans, a partner at Arch Ventures, while speaking on a panel.
"Equally, there are lots of areas of oncology where there is incredible need and there is nothing there," he said, pointing to cancers like acute myeloid leukemia — an area of familiarity from his time as head of corporate development and portfolio leadership at Agios Pharmaceuticals.
Alexis Borisy, a partner at Third Rock Ventures, largely seemed to share the same view. For Borisy, as long as many cancers continue to be fatal for most people, companies that have a clear hypothesis and the tools to study it will represent a compelling investment.
A crowded class
It's in immunotherapy, however, where activity has run the hottest. Already five checkpoint inhibitors blocking the PD-1/L1 pathway are approved in the U.S., with an estimated 40 more wending their way through clinical development, according to a recent analysis by the Cancer Research Institute.
Approved PD-1/L1 inhibitors
|Drugmaker||First approval||# of cancer types approved for|
|Keytruda (pembrolizumab)||Merck & Co.||Sep. 2014||7|
|Opdivo (nivolumab)||Bristol-Myers Squibb Co.||Dec. 2014||8|
|Tecentriq (atezolizumab)||Roche AG||May 2016||2|
|Bavencio (avelumab)||Merck KGaA||March 2017||1|
|Imfinzi (durvalumab)||AstraZeneca plc||May 2017||2|
In 2009, a lone combination study of a PD-1/L1 blocker with another drug kicked off. Last year, by comparison, nearly 500 combination trials were initiated, targeting a cumulative enrollment of more than 50,000 patients.
"The concentration of I/O development and patient resources on a few targets, some with already approved drugs, could potentially be stalling future innovation," cautioned the researchers from CRI in a paper published in the Annals of Oncology two months ago.
Drugmakers could be forgiven for overly focusing on PD-1/PD-L1 inhibitors. Merck & Co.'s Keytruda (pembrolizumab) and Bristol-Myers Squibb Company's Opdivo (nivolumab) have found runaway commercial success, each cresting $1 billion in sales per quarter. Both are approved across a broad range of cancers and seem to offer wide potential as a backbone therapy in combination treatment.
It's hard to imagine a market, though, where half a dozen or more similar checkpoint inhibitors are all successfully marketed. But that hasn't stopped companies like Sanofi and Novartis AG from developing their own.
"Is there a need for nine of them? I'm not sure. But they are a platform therapy," remarked Jay Bradner, president of the Novartis Institutes for BioMedical Research while on a panel at the conference. "Of course they are not for everybody and in themselves are not curative. But they do pair really well and we have already seen at Novartis bring out the best in a second agent."
Sanofi, together with its partner Regeneron Pharmaceuticals Inc., is currently developing a PD-1 inhibitor known as cemiplimab across several different cancer types. The companies hope to gain a foothold in the cancer immunotherapy market by aiming first at cutaneous squamous cell carcinoma, an indication overlooked by others.
"We think that's our opportunity to go in an introduce this drug to doctors as a new option for patients who didn't have a treatment option before," said Joanne Lager, head of development at Sanofi Oncology, in an interview.
"With lung, we are not going to go in and take over the market. But we think there is room for another option in that setting. The plan is to build on that with novel combinations to improve outcomes for those patients," she added.
Can't say no
As long as the immunotherapy field remains unsettled, it appears drugmakers remain confident in their ability to first find a market niche and then build on that foundation with combination treatment.
Yet even if the next PD-1/L1 developer is successful, the company will still need to identify or develop an effective partner therapy. So far, despite the collective efforts of the industry, only a handful of approved drug combinations involving immunotherapies have emerged.
Not every company in the space will be able to find the right pairing, meaning some pharmas will end up on the outside looking in. The pace of innovation in translational medicine, however, appears too enticing for companies to say no.
"This an era of appropriate investment," said Bradner. "There is profound unmet need. There is clarifying biology. There is a huge denominator of hypotheses to test."