AZ, Daiichi's new cancer drug Enhertu gets off to the races with quick U.S. launch

What do you get when you add a drug with clear clinical benefits, an extremely early FDA nod and two well-prepared sales teams? In Daiichi Sankyo and AstraZeneca’s HER2-targeting med Enhertu’s case, a potential $18 million in sales during the first quarter of launch.

Daiichi Sankyo U.S. chief Ken Keller made that projection during a recent interview with FiercePharma. It would mark an auspicious start for a drug that’s currently cleared only for patients who have failed on two other therapies.

“We track sales every day and we track the number of physicians that … have acquired the drug, and right now I can tell you we’re very happy with where we are right now,” he said.

Well-prepared sales teams

The FDA gave the two companies a pleasant surprise on Dec. 20 by granting Enhertu an accelerated approval to treat third-line HER2-positive breast cancer patients. That nod came just two months after the companies filed for approval—in other words, four months ahead of schedule.

But despite the early decision, Daiichi and AZ were “100% ready.”

Within two days, both companies’ dedicated Enhertu sales teams were completely trained and were already talking to physicians, Keller said. The first commercial patient was treated on Jan. 2, immediately after the holidays.

The two companies have been engaged in a 50-50 partnership since AZ splashed a hefty $1.35 billion upfront payment to license the antibody-drug conjugate. On the commercial side, they have their own customer-facing teams that consist of sales reps, medical affairs liaisons, nurse education specialists and others focused on access and reimbursement.

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Sales reps from both companies would see the same customers. “We believe what will happen is as Enhertu gains additional indications over time, we will have these two reps focused on different indications,” Keller said. “But today for the introduction, there’s so much work in education to that, that it actually makes sense for the first launch.”

But the setup does leverage AstraZeneca’s cancer experience. For example, AZ’s leading the charge for payer discussions in the U.S.

Daiichi hadn’t had an oncology drug for some time after it and Roche’s Genentech ceased promotional activities for BRAF inhibitor Zelboraf in 2017. That ended in 2019 with an FDA green light for Turalio to treat the rare disease of symptomatic tenosynovial giant cell tumor (TGCT).

Selling Turalio and Enhertu requires very different strategies, said Keller, who last year expanded his U.S. commercial chief title to become Daiichi U.S.’s president and CEO, just as the company pivoted to oncology.

For Turalio, only a small number of sales staffers are needed to cover the full opportunity. Their focus is sarcoma oncologists and educating surgeons who can refer patients not suitable for surgery to those specialists.  

“Unlike Turalio where those patients are hard to find, every oncologist in the U.S. unfortunately has a number of [breast cancer] women who have exhausted all their options,” Keller said. “They have tried Herceptin, they tried Kadcyla, and they continued to advance … Those are the patients that the doctors are putting on Enhertu right away.”

Taking on HER2 leader Roche

Roche is the competitor to beat in HER2 breast cancer. The Swiss pharma doesn’t just have one drug, it has an entire HER2 portfolio, built off megablockbuster and standard-of-care Herceptin, followed by another antibody therapy Perjeta and its own ADC Kadcyla. Combined, those three products generated sales of a whopping CHF 10.95 billion ($11.21 billion) in 2019.

How can the Daiichi-Astra pair carve out a meaningful share from such a dominant market player? With an unbeatable clinical profile, Keller says.

Although both Enhertu and Kadcyla use the same HER2-targeting antibody—trastuzumab, or Herceptin—to track down the tumor, they use different payloads and linkers. That could make all the difference, he argued.

“The beautiful thing about oncology is it’s not the company that matters most, it’s the data that matters most, and our clinical data is causing physicians to want to use [Enhertu] very quickly,” Keller said.

In the phase 2 Destiny-Breast01 trial, Enhertu triggered a response in 60% of patients who had already failed Herceptin and Kadcyla. The response rate has raised eyebrows in this heavily pretreated patient group, and what physicians find most appealing is the drug’s long duration—it can stall tumor progression or death by 16 months.

“When we show physicians the 16 months, it literally stops them in their tracks and the questions quickly become, how do I get this drug, how do I infuse it, talk to me more about the safety profile, because the clinical efficacy is so unquestionable,” Keller said.

Kadcyla came to life bearing peak sales estimates as high as $5 billion, but last year it racked up CHF 1.39 billion ($1.42 billion). The main setback is that the drug failed to leapfrog Herceptin to reach earlier patients. It recently got a go-ahead as a treatment used after surgery for people with residual invasive disease after pre-surgery treatment with Herceptin. But in the Marianne study, Kadcyla was only non-inferior to Herceptin in previously untreated patients.

Daiichi and AZ are hoping to beat Kadcyla through their clinical programs. It’s running a head-to-head study against Kadcyla in the second-line setting to show superiority. A successful readout “should give us a lot of leverage to replace Kadcyla,” Keller said.

In addition, it’s also looking to take Enhertu places that Kadcyla and other HER2-targeted drugs have failed to go. A few days ago, Daiichi and AZ said topline results from the phase 2 Destiny-Gastric01 study showed that Enhertu improved overall survival compared with chemo in late-line HER2-positive gastric cancer. Previously, Kadcyla had flunked a second-line stomach cancer trial.

Although stomach cancer is a small indication, Keller argued it allows Daiichi to create “a very nice halo” around Enhertu to be able to say it’s able to show efficacy at places Kadcyla never did.

The third, in what Keller called “the most exciting near-term opportunity,” is the low HER2-expressing breast cancer, a population that according to him is 2.5 times that of the current HER2-positive market. If Enhertu eventually gets there, it could have that market to itself, given there’s no anti-HER2 drug approved for these patients, who have no good options after CDK4/6 inhibitors.

Daiichi also has AZ to lean on. And the British drugmaker has two top breast cancer experts recruited on its leadership team, CLSA analyst Tony Ren recently noted.

José Baselga, AZ’s oncology R&D chief, has a special interest in breast cancer and was physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center before joining the company. AZ’s head of breast cancer strategy and global clinical leader in oncology R&D is Sunil Verma, who was the lead investigator for the first ADC to be approved for breast cancer and worked on clinical trials in CDK4/6 inhibitors and immuno-oncology agents.