Immunomedics finally wins its blockbuster FDA nod for Trodelvy in triple-negative breast cancer

Two manufacturing slapdowns and the ongoing pandemic didn’t stop the FDA from doling out an early drug approval to Immunomedics' antibody-drug conjugate Trodelvy.

Also known as sacituzumab govitecan, the drug won accelerated FDA nod as a third-line treatment for metastatic triple-negative breast cancer more than a month ahead of schedule, taking its first major step toward the $1.44 billion in 2024 sales projected by Evaluate Pharma.

The go-ahead comes at a delicate and complicated time. The COVID-19 crisis has already prompted Bristol Myers Squibb to postpone the launch of its Celgene-inherited multiple sclerosis drug Zeposia. But Immunomedics has no intention of stashing Trodelvy away.

“Triple-negative breast cancer is not slowing down or taking a break because of COVID-19. Patients are going to need treatment, especially patients who are progressing rapidly from earlier lines of treatment,” Immunomedics Chief Commercial Officer Brendan Delaney said in a recent interview with FiercePharma. “We have an obligation as a company and also as a commercial organization to educate the market as quickly as possible.”

To attack tumors, Trodelvy uses an antibody to target Trop-2—a cell-surface receptor that’s over-expressed by many tumors, including TNBC—and deliver a toxic payload, SN-38, the active metabolite of chemotherapy irinotecan.

Data from a phase 1/2 study showed the ADC shrank tumors in about 33% of TNBC patients who had received a median of three prior lines of treatment, with the response lasting for a median 7.7 months. It also delayed the time to tumor progression or death for a median 5.5 months and helped these heavily pretreated patients live 13.0 months, according to results published in The New England Journal of Medicine.

What’s more, Immunomedics recently said the drug's phase 3 confirmatory study, dubbed Ascent, was stopped early on “compelling” evidence of efficacy observed by an independent data monitoring committee. That data could help the company turn the conditional nod into a full one.

In comparison, mainstay chemotherapies historically deliver response rates of 10% or less, and they've proven able to fend off progression from 1.5 months to 2.5 months, Delaney said.

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But Trodelvy has faced plenty of other hurdles. The FDA shot down the drug early last year because of manufacturing problems later detailed in an FDA Form 483. That document unveiled big problems with data integrity at the company’s New Jersey plant where the ADC is made.

That letdown triggered a C-suite overhaul as then-CEO Michal Pehl and R&D head Robert Iannone hit the exit. The top job was just filled this month by Harout Semerjian, who most recently served as Ipsen’s chief commercial officer and previously spent 16 years at Novartis Oncology. Johnson & Johnson veteran and recent Medicines Company exec Loretta Itri signed on as chief medical officer in February.

Then, after investors’ hope was rekindled by Immunomedics’ refiling the Trodelvy application, the FDA once again slapped a Form 483 (PDF) on the New Jersey plant in a pre-approval inspection a few weeks ago.

This time, the 10 observations covered concerns about inadequate standard operating procedures and other control measures. The citations didn't directly raise doubts about Trodelvy’s quality.

During a conference call in early April, management said the company had submitted their Form 483 response to the FDA. Wednesday's approval suggests the FDA accepted Immunomedics' redemption plan.

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Now that the approval is in hand, the company can roll out its new med, if not in the way it had originally planned.

Even before the original rejection, Immunomedics had built up a salesforce fully prepared to promote Trodelvy, Delaney said. By quickly signing a one-year contract to help market Johnson & Johnson’s cancer drug Balversa in bladder cancer, the company was able to preserve most of its commercial organization, which is now 130-strong, according to Delaney. After a previous $2 billion Seattle Genetics deal went south in 2017, Delaney said the company intends to launch the drug in the U.S. on its own, though it's in discussions about possible European tie-up.

That Balversa deal might eventually benefit Immunomedics in other ways as the company looks to expand Trodelvy’s label. The ADC’s potential use in bladder cancer recently nabbed an FDA “fast track” designation. Interim results from the phase 2 Trophy U-01 study showed a 29% overall response rate among the first 35 patients, who had relapsed or are proved resistant to PD-1/L1 drugs and platinum chemotherapy.

Beyond that, the company is pairing Trodelvy with Roche’s Tecentriq in patients with previously-untreated TNBC. Last year, the Roche immuno-oncology agent picked up a first-in-class nod to be used alongside the chemo drug Abraxane for new TNBC patients whose tumors express PD-L1. Immunomedics has also expanded its Trophy U-01 study to include a cohort to test the combination of Trodelvy with Merck & Co.’s Keytruda.

Meanwhile, in China, Everest Medicines, through a potentially $835 million licensing agreement with Immunomedics, has just won regulatory clearance to run a local trial in TNBC