Although it took a while, targeted cancer drugs lived up to the hype | Mint

Although it took a while, targeted cancer drugs lived up to the hype

Scientists seem to have determined the right design for making the drugs sufficiently safe and highly effective.
Scientists seem to have determined the right design for making the drugs sufficiently safe and highly effective.


  • The tumour targeting of chemotherapy has gotten both sharper and safer. These advancements could rewrite the cancer treatment playbook.

Cancer drugs that deliver chemicals directly to tumours are having a bit of a moment. Pharmaceutical companies are making these so-called antibody-drug conjugates the technology of choice in oncology deal-making, as illustrated by last week’s $10.1 billion acquisition of ImmunoGen by AbbVie.

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’s proposed $43 billion buyout of Seagen, Merck & Co’s $4 billion tie-up with Daiichi Sankyo, and a series of smaller investments from Bristol-Myers Squibb and Eli Lilly & Company.

It has taken a while to get here.

ImmunoGen has been 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 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 tumour.

A real turning point came in mid-2022, when AstraZeneca and Daiichi Sankyo showed that their wonder drug, Enhertu, could extend the lives of women with advanced breast cancer by six months compared with conventional chemotherapy. 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 neighbouring tumour 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. Exploiting it could open up the field for these drugs. Pharma companies can now imagine using them in a broader range of tumours 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 tumours 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 focus on immunotherapies or newer drugs that can be used alongside them.

According to the US 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 have largely struggled to find novel therapies that work, let alone come close to matching Keytruda’s broad efficacy.

Smarter chemo, though? Each new dataset on antibody-drug conjugates solidifies the case that the technology could be much more broadly used than previously anticipated. When the Enhertu data first surfaced last year, several oncologists told me they thought antibody-drug conjugates could eventually play a much larger role in cancer treatment—and even replace conventional chemo altogether in some types of cancer. Pharma companies believe that’s possible, too. “The Daiichi AstraZeneca effect has been real," Lambert said.

It’s a good reminder that old concepts can truly be made new again. It just might take a few decades. ©bloomberg

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