Reuters
Pharmaceutical companies have tried and failed to develop a drug that targets common mutations in the KRAS gene for three decades.
- Pharmaceutical companies long wanted to develop a drug that would target KRAS, a common gene mutation seen in cancers. But every effort so far has failed.
- The pharmaceutical company Amgen and biotech Mirati are backing two new drugs that are raising those hopes again, though it's still early days.
- If these experimental products are successful, they could rake in billions in sales and help patients with few treatment options.
The pharmaceutical industry has spent 30 years and wasted billions of dollars chasing a type of cancer drug in a quest that some have declared impossible.
Today, though, it's back, with two drugmakers racing to see if theirs is the winning approach. Though it's early days still, their focus and potential has the industry abuzz.
There is "huge enthusiasm for figuring out how to drug that pathway," SVB Leerink analyst Andy Berens told Business Insider. He called this and another cancer-fighting approach "probably the silver bullet," adding that it "would be a tremendous victory for biotech and oncology, if it works."
Behind all this is the KRAS gene, which works in the body as a traffic light that signals the go-ahead for cells to grow and change. Mutations in the gene, though, could turn cells cancerous - and give them the green light to grow explosively.
Indeed, KRAS mutations are common, seen in lung, pancreatic and colorectal cancers, among others.
Stopping that mechanism has been the aim of scientists for a long time, but their lack of success has led many to think that it is "undruggable."
One of those companies is also leading the renewed focus on KRAS: the $23 billion pharmaceutical company Amgen. Amgen has started testing its drug, AMG 510, in humans in a early-stage research trial, and initial results - expected this summer at a prominent cancer-research meeting - are hotly awaited.
If the drug is promising, Wall Street expects sales of at least $1 billion or $2 billion a year.
The $2.5 billion biotech Mirati Therapeutics is also racing to develop its own KRAS-targeting drug, and its shares have surged nearly 65% since the start of the year, when Amgen began talking up the potential of AMG 510. Mirati hasn't yet tested its product in humans but isn't far behind, analysts say.
A discovery made from a 'library' of new potential drugs
Amgen believes that AMG 510 works in a unique way that makes it more powerful, and thus could set it apart from other, failed drug development efforts.
The experimental drug came out of a collaboration that the pharmaceutical company had with the Berkeley, California-based biotech Carmot Therapeutics, developing "libraries" of new molecules that could one day be new drugs.
The companies focused that effort on a specific mutation, KRASG12C. Amgen estimates that it is a relatively common mutation, making up about 12% of all KRAS mutations across different types of "solid tumor" cancers.
Amgen is interested in studying the drug in lung cancer and likely in colorectal cancer, as well as other solid tumors.
What excited the company about AMG 510 was way it behaved with the protein, doing a type of dance that opened up a flap in the molecule and exposed a deep pocket.
That pocket lets the drug get in, where it should be able to keep a firm hold and prevent KRAS from giving that "green light," explained Dr. PK Morrow, Amgen global product general manager and team lead for AMG 510.
Potential in lung and colorectal cancers
If it works, it could be an option for patients with non-small cell lung cancer, the most common type, for example, as a second or third treatment option where "the options are often quite limited," Morrow said.
"This has been a program that has created within our company such a sense of true excitement and gratification for being able to develop something that has the potential to help patients in such grievous need," Morrow told Business Insider.
AMG 510 also has potential as a combination, Amgen believes, and is being studied in animal research with another Amgen drug, Vectibix, something that could potentially be used in colorectal cancer.
But, like with all drug development, there's no guarantee that these results will be as promising in humans.
And being able to block the KRAS pathway, meanwhile, "doesn't necessarily mean it'll translate to the tumor dying and patients having improved outcomes," SVB Leerink's Berens said.
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