It’s not often that medicine gets a standing ovation. When Daiichi Sankyo and AstraZeneca announced surprising results for breast cancer treatment Enhertu, oncologists stood to applaud.
“It was a goosebump moment, it sent shivers down my spine,” said Susan Galbraith, who leads oncology research and development at AstraZeneca.
Ken Keller, chief executive of AZ’s Japanese partner on the drug, purposely stopped from his team at the American Society of Clinical Oncology meeting to see the mood of the crowd. “People usually have tears of joy in their eyes,” he said.
But the man who had brought the two companies together – oncology pioneer José Baselga – did not live to witness the reception of the drug. He died in 2021 at the age of 61 from a rare brain disease.
One in eight women will develop breast cancer in their lifetime – and Enhertu has the potential to change treatment for half of them. David Fredrickson, executive vice president of the oncology business at AstraZeneca, said the drug “blows away the swimming lane” that previously defined breast cancer treatment. For a large group of patients, he said, it may be “one of the most important drugs”.
Enhertu was first approved in the US in 2019 for a subset of cancer patients with high levels of a protein called HER2. About 15 to 20 percent of breast cancers are HER2 positive, but a trial last June showed that the drug can double the time patients can live without the cancer progressing, even when levels of the protein are low. About a fifth of participants with metastatic cancer – usually seen as incurable – had a complete response: the scan failed to detect the tumor.
The drug has turned Daiichi Sankyo into an oncology company. And this is further evidence that AstraZeneca, a leader in the field, knows when to strike: the unusual step of raising $3.5bn in the public market to help pay for a $6.9bn deal to develop and sell the drug appears to have more than paid off. dead. Analysts forecast about $10bn a year in Enhertu sales at its peak.
In 2005, Daiichi joined Sankyo, bringing together chemists from the former and biologists from the latter who would create Enhertu.
The drug builds on a history of targeting the HER2 protein that began when Roche launched Herceptin in 1998. Like Herceptin, scientists use artificial antibodies to bind to the HER2 protein in cancer cells. But they improved the current treatment by creating a strong link to a more powerful molecule that destroys enzymes and kills cancer cells.
When they tried it on mice, they could see that it worked better than the market leader, Roche’s Kadcyla. But Daiichi has never developed a cancer drug. “Finally, science won out the other day,” said Ken Takeshita, head of global R&D at Daiichi. “It’s brave for this company to say, we’re going to get rid of being a cardiovascular company.”
Keller wishes he could say he knew about the drug’s promise at the time. In about 2015, the technology began to look “quite spectacular”. “But there are a lot of drugs that look spectacular in animal studies,” he said.
He was even more confident after his first study in humans: a hard-to-treat population that has tried several other drugs. “At that time, almost nothing worked. And we saw the tumor shrink very much,” he said.
Keller considered the chief executive at the time, George Nakayama, by making two big bets: focusing on the company in Enhertu, and working with AstraZeneca.
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Baselga joined AstraZeneca in early 2019 as head of oncology research and development. He was forced to resign as chief physician at the Memorial Sloan Kettering cancer center in New York for failing to disclose payments from the healthcare company, which the American Association for Cancer Research later concluded was “inadvertent”.
But while there, he has led a phase 2 trial for Enhertu, seeing firsthand how it helps patients. In his first week at AstraZeneca, he pushed the idea that AstraZeneca should have a partnership with Daiichi.
Fredrickson said Baselga’s extensive experience studying breast cancer meant he and AstraZeneca chief executive Pascal Soriot sat down and listened. Soriot has turned AstraZeneca into an oncology powerhouse, producing blockbusters like Tagrisso and Lynparza.
“José really gave me confidence that this is a drug that should be part of AstraZeneca,” Fredrickson said.
Daiichi split the rights 50/50 with AstraZeneca, outside of Japan, in return for AZ conducting further clinical trials. Michael Leuchten, an analyst at UBS, said it was a “very smart deal”. “What is AstraZeneca seeing that others are missing?” he asked, adding that the company has proven time and time again that it can make good decisions.
For Daiichi, AstraZeneca offers oncology expertise and money. To maximize Enhertu’s potential, they are planning 40 trials, one of the largest programs in the industry. He asked an unanswered question: does Enhertu work in the early stages of breast cancer? It has been approved for some other types of cancer like stomach and lung, where HER2 is seen; but how many others can intercept?
“We have so many potential cancers that we can study and sometimes it’s a bit difficult to find all the people and all the resources,” Takeshita said.
The biggest chance is early stage breast cancer. The earlier the cancer is treated the better, so it can make a bigger difference.
Nick Turner, an academic consultant medical oncologist at the British Institute of Cancer Research, who specializes in breast cancer but was not involved in the Enhertu trial, said that there is a possibility in the future that oncologists will prescribe Enhertu instead of the previous standard medicine. Kadcyla.
“Then we will treat the majority of early-stage HER2-positive breast cancer patients,” Turner said.
Roche said that Kadcyla will still be an important option for patients, with an established record of safety and efficacy, and that the company is exploring using the drug in combination with other cancer drugs.
However, Enhertu has significant side effects. Patients often have the same side effects known from chemotherapy – such as sickness and hair loss – and there is a smaller risk of developing serious lung conditions. Patients in the early stages tend to take the drug longer and it may be difficult to tolerate it in the long run.
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Daiichi also makes other drugs based on the same platform as Enhertu, one of which is also part of a partnership with AstraZeneca. Gareth Powell, head of healthcare at specialist fund manager Polar Capital, said Enhertu had helped take AstraZeneca to a “whole new level in terms of growth potential” – and while the sales took off, it would ultimately improve margins at Daiichi.
“At some point, this product becomes so big, you can’t spend it quickly in terms of investment,” he said.
Analysts at Credit Suisse in London said the competition was at least three years away. He believes that all platform-based treatments that combine antibodies with molecules to kill cancer cells in the pipeline are successful, adding to opportunities like Merck’s blockbuster oncology drug Keytruda, which has sales of $17.2bn in 2021. But he warns that investors’ expectations are too high, so if something is wrong, it might hit the stock in AstraZeneca.
For patients, Enhertu promises time. Emma Fisher was diagnosed with breast cancer in 2016 at the age of 35, and two years later, she learned that it had spread. The average life expectancy of a person with secondary breast cancer is two to five years.
Fisher’s private health insurance paid for the drug, but he testified at the UK’s National Institute for Clinical Excellence to try to persuade authorities to pay for it for everyone on the NHS. NICE currently covers the drug for most HER2-positive breast cancer patients, and will consider it for cancers with low levels of HER2 in 2023.
“Twelve months is a very long time. It may not seem like a lot of time for people who do not have incurable cancer. But for people with incurable cancer, 12 extra months is everything,” he said.