Cancer drugs that work like heat-seeking missiles to deliver chemicals directly to tumors are having a bit of a moment. Pharmaceutical companies, in need of assets to counter flagging sales, are making these so-called antibody-drug conjugates the technology of choice in oncology dealmaking, as illustrated by last week’s $10.1 billion acquisition of ImmunoGen Inc. by AbbVie Inc.
If that trend sounds vaguely familiar, you have probably been following the pharma industry for too long. The field has gone through waves of hype and investment over the past several decades. This time, though, the hype is deserved.
After decades of fits and starts, the science around designing and testing this class of drugs has finally coalesced. The concept of deploying powerful chemo drugs to cancer cells in a targeted, safer way always made sense; now, companies know how to do it in a manner that could make them a staple of cancer care.
That’s reflected in pharma companies’ sudden deep commitment to the space. In addition to AbbVie’s acquisition, other deals this year include Pfizer Inc.’s proposed $43 billion buyout of Seagen Inc., Merck & Co.’s $4 billion tie-up with Daiichi Sankyo Co., and a series of smaller investments from Bristol-Myers Squibb Co. and Eli Lilly & Co.
It has taken a while to get here. Consider that ImmunoGen has been plugging away at its smart-bomb technology for longer than some biotech executives have been alive. Formed in 1981, the company has survived many peaks and valleys in its pursuit of antibody-drug conjugates. At one point, it had chugged along so long that one New York Times reporter included it in a list of “zombie biotechs,” companies churning through cash for decades without ever turning a profit. While a drug developed by one of its partners that used its technology was approved in 2013, ImmunoGen didn’t have its own product—Elahere, for advanced ovarian cancer—on the market until last year.
But the slog has finally paid off. Scientists seem to have determined the right design for making the drugs sufficiently safe and highly effective. That’s something of an art that involves picking the right antibody to home in on a cancer cell and settling on the right type of chemotherapy to knock it out. The most vexing piece, though, has been engineering the link between those two parts—one that holds tight while the drug circulates in the blood but releases when it reaches a tumor.
The most recent advance has come from simply understanding the best use of these drugs.
A real turning point came in mid-2022, when AstraZeneca and Daiichi Sankyo showed that their drug, Enhertu, extended the lives of women with advanced breast cancer by six months compared with conventional chemotherapy. Moreover, the drug was being tested in women whose breast cancers had low, at times barely detectable levels of HER2, the protein that the drug homes in on before releasing its chemo. That suggested some of its power comes not only from its ability to kill cells expressing HER2, but the chemo’s ability to take out neighboring tumor cells, too.
This bystander killing seems to be an important component of good activity, said John Lambert, who consults for a number of companies on antibody-drug conjugates and previously was the chief scientific officer at ImmunoGen. And exploiting it could really open up the field for these drugs. Pharma companies now can imagine using them in a broader range of tumors than previously anticipated. Moreover, Lambert said, it might also open up the design of drugs that use previously discounted antibodies—ones that targeted proteins that before weren’t considered to be expressed at high enough levels in tumors to be effective.
All of this is a welcome refresh for the oldest trick in the cancer playbook: chemo. Drug companies have spent the last decade scouring the landscape for the next big thing in cancer, with a particular focus on immunotherapies or newer drugs that can be used alongside them. According to the Center Research Institute, by late 2021, some 4,900 clinical trials were underway for so-called checkpoint inhibitors, a class that includes Merck’s top-selling drug Keytruda. But they’ve largely struggled to find novel therapies that work, let alone come close to matching Keytruda’s broad efficacy.