It’s not normal for Aqar to get a standing ovation. But when Daiichi Sankyo and AstraZeneca announced impressive results for their breast cancer treatment, Enherto, oncologists stood up in applause.
“It was a chilling moment,” said Susan Galbraith, who leads oncology research and development at AstraZeneca. “I felt goosebumps run down my back.”
Ken Keller, chief executive officer of AstraZeneca’s Japanese partner in the pharmaceutical firm, deliberately stood out from his team at the American Society of Clinical Oncology meeting to see the mood of the crowd. He said, “There were tears of joy in people’s eyes.”
But the man who brought the two companies together — oncology pioneer Jose Basilga — didn’t live to see the drug’s acceptance. Basilja died in 2021 at the age of 61 from a rare brain disease.
One in eight women will develop breast cancer in her lifetime, and enherto has the potential to change the treatment pathway for half of them. David Fredrickson, executive vice president of oncology at AstraZeneca, said the drug “blows up pathways” that previously drove breast cancer treatment. For a large group of patients, he added, this could be “one of the most important drugs of all.”
Enherto was first approved in the US in 2019 for a subset of cancer patients who have high levels of a protein called HER2. About 15-20 percent of breast cancer cases contain the protein HER2, but a study last June showed the drug could double the time patients could live without developing cancer, even if they had low levels of this protein. protein. About one-fifth of participants with metastatic cancer, which is usually considered incurable, had complete responses. X-rays were unable to detect their tumors.
The drug transformed Daiichi Sankyo into an oncology company. This is further proof that AstraZeneca, a leader in the sector, knows when to seize opportunities. His unorthodox move to raise $3.5 billion in public markets to help pay for the development and sale of the $6.9 billion property may have more than met its goal. Analysts expect Inherto’s sales to peak at about $10 billion annually.
In 2005, Daiichi Corporation merged with Sankyo, bringing together chemists from the former and biologists from the latter who would continue to produce Inherto.
The drug builds on a history of targeting the HER2 protein that dates back to Roche’s release of Herceptin in 1998. Just as with Herceptin, the scientists used a synthetic antibody to bind the HER2 protein to a cancer cell. But they have improved existing treatments by creating a strong bond with an even 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 the leading drug on the market, Roche’s Kadcyla. But Daiichi has never produced a cancer drug. “Ultimately, science won out at that time,” said Ken Takeshita, global head of research and development at Daiichi.
Keeler wished he could say he knew how promising the drug was at that point. Around 2015, the technology had started to get “pretty amazing.” “But there are a lot of drugs that look amazing in animal studies,” he said.
He was even more convinced after the first study in humans, a group of difficult-to-treat conditions for which many other drugs have been tried. “At that point, almost nothing worked,” he said. “We could see the tumor shrink dramatically.”
Keller credits George Nakayama, the CEO at the time, for making two big bets, focusing the company on Inherto and working with AstraZeneca.
Basilja joined AstraZeneca in early 2019 as Head of Oncology R&D. He had been forced to resign his position as chief physician at Memorial Sloan-Kettering Cancer Center in New York for his failure to disclose payments by health care companies, which the American Association for Cancer Research later concluded was “unintentionally “.
But while he was there, he was conducting Inherto’s Phase 2 study, seeing firsthand how it helped patients. In his first week at AstraZeneca, he promoted the idea that AstraZeneca should build a partnership with Daiichi.
Fredriksson said Basilja’s extensive experience studying breast cancer made him and Pascal Soriot, chief executive of AstraZeneca, sit up and listen. Soriot had already built AstraZeneca into an oncology powerhouse, producing blockbuster drugs like Tagresso and Linparza.
“José has given us complete conviction that this is a drug that AstraZeneca needs to be a part of,” said Fredriksson.
Outside Japan, Daiichi has equally split the rights with AstraZeneca in exchange for further clinical trials by AstraZeneca. It was a “very smart deal,” said UBS analyst Michael Lochten. “What did AstraZeneca see that others missed?” he asked, adding that the company has demonstrated time and again its ability to make good decisions.
For Daiichi, AstraZeneca provided oncology expertise and funding. To make the most of Inherto’s potential, the two companies plan to run 40 trials, one of the largest programs in the industry. Both companies raise important unanswered questions: Does Inherto work in the early stages of breast cancer? It’s already been approved for a few other cancers like stomach and lung cancer, where the HER2 protein appears, but how many other cancers can it treat?
“We have so many possible types of cancer that we can study, and sometimes it’s a little difficult to find all the people and all the resources,” Takeshita said.
The biggest possibility is breast cancer in its early stages. The sooner cancer is treated, the better, so it can make a bigger difference in the early stages.
Nick Turner, an academic consultant medical oncologist at Cancer Research UK who specializes in breast cancer but was not involved in the Inherto studies, said it was very likely that in future oncologists would prescribe Inherto instead of the usual predecessor drug, Kadcyla.
“We will then be well on our way to curing the vast majority of patients with early-stage HER2-positive breast cancer,” said Turner.
Roche said Kadcyla will continue to be an important choice for patients, with its strong record of safety and efficacy, and the company is exploring using it in combination with another of its cancer drugs.
However, Inherto has significant side effects. Patients often experience the same well-known side effects of chemotherapy — such as nausea and hair loss — and there’s a much lower risk of serious lung disease. Patients in the early stages tend to take the drug for a longer period of time and may have difficulty tolerating it over time.
Daiichi makes other drugs based on the same platform as Inherto, one of which is also part of a partnership with AstraZeneca. Gareth Powell, head of healthcare at fund manager Polar Capital, said Enherto has helped take AstraZeneca to “a whole new level in terms of growth potential” and, when sales take off, margins will eventually boost. by Daiichi.
“At some point, this product gets too big and you can’t go fast enough in terms of investment,” he said.
Analysts from Credit Suisse in London said the competition was at least three years behind. They believe that if all therapies based on the platform that combines antibodies with a molecule to kill cancer cells in the body are successful, it could add a huge opportunity such as Merck’s flagship oncology drug, Keytruda, which generated sales of 17.2 billion dollars in 2021. But they warned that investor expectations are already very high, so if something goes wrong, it could affect AstraZeneca’s shares.
For patients, Inherto promises to give them more time. Emma Fisher was diagnosed with breast cancer in 2016 when she was just 35, and two years later she discovered that she had metastasized. The average life span of a person diagnosed with secondary breast cancer ranges from two to five years.
Fisher was paid for the drug by private health insurer but testified before the UK’s National Institute for Health and Care Quality to try to get authorities to pay for the drug for all members of the NHS. The NIHQ now covers the drug for many patients with breast cancer that includes HER2 and will consider using it to treat cancers with low levels of HER2 in 2023.
“12 months is a very long time,” she said, “for someone who doesn’t have incurable cancer, that might not seem like a long time. But for someone with incurable cancer, another 12 months means everything.”