Seattle Genetics announced Friday that the FDA has approved its filing  for Tukysa (tucatinib), in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received at least one prior anti-HER2-based regimen in the metastatic setting. According to the FDA, the oral tyrosine kinase inhibitor is the first new drug approved under the international Project Orbis initiative, with the US regulator noting that it collaborated with its counterparts in Australia, Canada, Singapore and Switzerland on this review.
Tukysa will have a wholesale acquisition cost of $18,500 for a 30-day supply, Seattle Genetics said, with CEO Clay Siegall noting "our commercial and reimbursement teams are in place... We've been preparing for this launch now for months." SVB Leerink analyst Andrew Berens has projected peak sales of $1.2 billion for the therapy by 2030.
The FDA filing was backed by data from the placebo-controlled HER2CLIMB study, which enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab and ado-trastuzumab emtansine. Seattle genetics noted that 48% of patients in the trial also had a presence or history of brain metastases. The primary efficacy outcome measure was progression-free survival (PFS) in the first 480 randomised patients. Additional efficacy goals evaluated in all randomised patients included overall survival, PFS in patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).
The results , published in the NEJM and presented at the San Antonio Breast Cancer Symposium (SABCS) last December, demonstrated that the combination of Tukysa plus trastuzumab and capecitabine led to a 46% reduction in the risk of cancer progression or death, compared to trastuzumab and capecitabine alone, while the risk of death was cut by 34% among those in the Tukysa group. Further, nearly twice as many patients receiving the Tukysa combination treatment had a confirmed ORR, compared with trastuzumab and capecitabine alone, at rates of 40.6% and 22.8%, respectively. Moreover, in a subgroup of patients with brain metastases, the addition of Tukysa reduced the risk of cancer progression or death by 52% compared to trastuzumab plus capecitabine alone.
Seattle Genetics said serious adverse reactions occurred in 26% of patients who received Tukysa, with diarrhoea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting and abdominal pain being among the most common.
"We recognise that patients with cancer constitute a vulnerable population at risk of contracting the coronavirus disease," commented Richard Pazdur, acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, noting that "Tukysa was approved four months prior to the FDA goal date [of August 20]…showing how our regular work in reviewing treatments for patients with cancer is moving forward without delay."
Meanwhile, Siegall indicated that Seattle Genetics did not expect disruptions to the supply of its therapies, including its two other approved cancer treatments, Padcev (enfortumab vedotin-ejfv) and Adcetris (brentuximab vedotin), due to the COVID-19 pandemic. The company is currently awaiting European approval for the Tukysa combination and is also testing the drug in other cancers such as colorectal cancer.