After Lisa Moore’s cancer treatments stopped working, the 64-year-old enrolled in a study to try out a new type of drug, one that is programmed to go after disease in cells in a novel way.
Moore is just one case. The kind of drug she tested in a late-stage trial has yet to be proven widely effective across large patient populations, but companies such as Bristol Myers Squibb, Pfizer and Roche are pouring billions of dollars into them, hoping to find a new tool to attack diseases from cancer to Parkinson’s. But some proteins are so flat that they are hard to latch on to. The first degrader to hit the market is Veppanu, a breast-cancer drug developed by Pfizer and Arvinas. Decades later, scientists repurposed the drug and its derivatives to safely treat cancer and leprosy. In studying it further, researchers discovered it was a protein degrader—the drug was able to destroy a problem protein by binding it with the right enzyme to attack a disease. Bristol Myers is seeking approval of another degrader, called mezigdomide, targeting the disease. This is the drug that Moore, the cancer patient, was taking.
These elusive, smooth proteins are involved in 85% of disease drivers that researchers have so far been unable to attack. The therapy, which was approved in May, works in patients with a specific genetic mutation called ESR1 who have failed hormone therapy, which represents around 1% of all newly diagnosed breast-cancer patients globally. The drug didn’t prove as effective in a wider population of breast-cancer patients whose tumors weren’t explicitly driven by the ESR1 mutation, a failure that led to a 53% stock selloff for Arvinas. Arvinas and Pfizer ended up unloading the drug to Rigel Pharmaceuticals for $70 million. In May, the company announced that mezigdomide in combination with other treatments led to patients living 18 months without progression , versus eight months in those on existing treatments.
A new class of medications—known as “protein degraders”—are showing promise in going after a certain kind of hard-to-target protein in diseased cells. Most medicines on the market today work by latching onto the rough surface of a protein and blocking it from causing disease.
In August, Bristol Myers Squibb received approval for a next-generation multiple myeloma treatment, Zenbexus, that works as a form of molecular glue. In clinical trials , severe multiple myeloma patients who took Zenbexus on top of two existing treatments lived 42 months before their cancer got worse, compared with 20 months for those without Bristol’s drug.
