A pharmaceutical partnership that brought about a breakthrough in breast cancer
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It’s not often that a drug receives a standing ovation. When Daiichi Sankyo and AstraZeneca announced impressive results for their breast cancer treatment Enhertu, oncologists rose to applaud.
“It was a goosebumps moment that sent shivers down my spine,” said Susan Galbraith, AstraZeneca’s director of oncology research and development.
Ken Keller, executive director of AZ’s Japanese partner for the drug, purposely stood apart from his team at the American Society of Clinical Oncology meeting to see the mood of the crowd. “People basically had tears of joy in their eyes,” he said.
But the man who brought the two companies together – pioneering oncologist José Baselga – did not live to see the drug’s reception. He died in 2021 at the age of 61 from a rare brain disease.
One in eight women will be diagnosed with breast cancer in their lifetime – and Enhertu has the potential to transform treatment for half of them. David Fredrickson, executive vice president of AstraZeneca’s oncology business, said the drug is “breaking the swim lanes” that previously defined breast cancer treatment. For a large group of patients, it could be “one of the most important drugs of all”.
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 study last June showed the drug could double the time patients can live without their cancer getting worse, even if they have low levels of this protein. About a fifth of participants with metastatic cancer – which is usually considered incurable – had a complete response: scans failed to detect their tumors.
Vials of Enhertu on a production line © Daiichi Sankyo/AstraZeneca
The drug turned Daiichi Sankyo into an oncology company. And it’s further proof that AstraZeneca, a leader in the space, knows when to strike: its unorthodox move to raise $3.5 billion in the public markets to match the $6.9 billion Funding dollar deal to develop and sell drug appears to be more than paying off. Analysts are forecasting Enhertu sales at their peak of about $10 billion a year.
In 2005, Daiichi merged with Sankyo, bringing together chemists from the former and biologists from the latter, who later formed Enhertu.
The drug builds on a history of targeting the HER2 protein that stretches back to Roche’s launch of Herceptin in 1998. Just like with Herceptin, the scientists used an artificial antibody to attach itself to a cancer cell’s HER2 protein. But they improved current treatments by making a powerful link to a more powerful molecule that breaks down enzymes and kills cancer cells.
When they tried it on mice, they could see that it worked better than Roche’s market leader Kadcyla. But Daiichi had never made a cancer drug before. “In the end, science prevailed back then,” said Ken Takeshita, global head of research and development at Daiichi. “It was brave of this company to say that we will move away from being a cardiovascular disease company.”
Keller wished he could say he knew how promising the drug was at the time. Around 2015, the technology looked “pretty spectacular.” “But there are many drugs that look spectacular in animal studies,” he said.
After the first human study, he was more convinced: a difficult-to-treat population that had tried several other drugs. “At this point almost nothing works. And we saw the tumor shrink dramatically,” he said.
Keller credits then-CEO George Nakayama with two big bets: the company’s focus on Enhertu and its collaboration with AstraZeneca.
Baselga joined AstraZeneca in early 2019 as Head of Oncology Research and Development. He had been forced to resign as chief physician at Memorial Sloan Kettering Cancer Center in New York for failing to disclose payments from healthcare companies, which the American Association for Cancer Research later found to be “unintentional.”
But while he was there, he had led the phase 2 trial for Enhertu and seen firsthand how it was helping patients. In his first week at AstraZeneca, he pushed the idea that AstraZeneca should partner with Daiichi.
Fredrickson said Baselga’s extensive experience in breast cancer screening meant he and AstraZeneca CEO Pascal Soriot sat up and listened. Soriot had already built AstraZeneca into an oncology powerhouse and produced blockbusters like Tagrisso and Lynparza.
“José really convinced us that this is a drug that AstraZeneca needs to be involved with,” said Fredrickson.
Daiichi split the rights 50/50 with AstraZeneca outside Japan in exchange for AZ conducting further clinical trials. Michael Leuchten, an analyst at UBS, said it was a “very, very smart deal”. “What did AstraZeneca see that others missed?” he asked, adding that the company has repeatedly proven it can make good decisions.
For Daiichi, AstraZeneca offered oncology expertise and money. To maximize Enhertu’s potential, they are planning 40 studies, one of the largest programs in the industry. They ask big unanswered questions: Does Enhertu work in earlier stages of breast cancer? It has already been approved for some other types of cancer, such as stomach and lung cancer, where HER2 occurs; but how many more could it handle?
“We have so many potential cancers to 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 sooner cancer is treated the better, so the sooner it could make an even bigger difference.
Susan Galbraith at AstraZeneca: “It was a goosebump moment that sent shivers down my spine” © Handout
Nick Turner, an academic consultant medical oncologist at the UK Institute for Research on Cancer who specializes in breast cancer but was not involved in the Enhertu studies, said it’s very likely that oncologists will prescribe Enhertu instead of the current standard drug in the future. Kadcyla.
“We will then be on our way to truly curing the vast majority of patients with HER2-positive early-stage breast cancer,” Turner said.
Roche said Kadcyla, with its proven safety and effectiveness, will continue to be an important option for patients, and the company is exploring using it in combination with another of its cancer drugs.
However, Enhertu has significant side effects. Patients often experience the same side effects known from chemotherapy — such as nausea and hair loss — and the risk of developing serious lung disease is much lower. Early stage patients tend to take a drug longer and they can have difficulty tolerating it over time.
Daiichi is also developing 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 helped take AstraZeneca to “a whole new level in terms of growth potential” — and if sales pick up, it would ultimately boost margins at Daiichi.
“Eventually this product becomes so big that you can’t invest in it fast enough,” he said.
Credit Suisse analysts in London say the competition is at least three years behind. They believe that if all treatments based on the platform, which combines antibodies with a molecule to kill cancer cells in the pipeline, succeed, it could lead to an opportunity as big as Merck’s blockbuster oncology drug Keytruda, which is 17 years old $.2 billion in revenue in 2021. However, they cautioned that investor expectations are already very high, so AstraZeneca’s shares could be hit if things go wrong.
Enhertu promises time for patients. Emma Fisher was diagnosed with breast cancer in 2016 when she was just 35, and two years later it was found 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 she testified before Britain’s National Institute of Clinical Excellence to try to persuade authorities to pay for it for everyone in the NHS. NICE now covers the drug for many patients with HER2-positive breast cancer and will consider it for cancers with low HER2 levels in 2023.
“Twelve months is a phenomenally long time. For someone who doesn’t have terminal cancer, that may not sound like a lot of time. But for someone with terminal cancer, an extra 12 months is everything,” she said.