As expected – and well ahead of the Aug. 20 PDUFA date – Bothell, Wash-based Seattle Genetics Inc. (Seagen) won FDA clearance for the oral small-molecule breast cancer therapy tucatinib, a tyrosine kinase inhibitor branded Tukysa.

Designed as highly selective for HER2 without significantly knocking down EGFR, Tukysa proved its mettle in what CEO Clay Siegall called “stunning” results from the HER2Climb study, which compared Tukysa in combination with Herceptin (trastuzumab, Roche Holding AG) plus capecitabine to Avastin/capecitabine in patients with locally advanced unresectable or metastatic HER2-positive disease. That’s the triple combo that won the go-ahead from U.S. regulators, who evaluated Tukysa under the Real Time Oncology Review pilot program, a setup “reserved, really, for the most striking and important drugs to come along,” Siegall said. Twice-per-day Tukysa in tablet form is indicated for patients who have received one or more prior treatments in the metastatic setting, an “all-important” broad label, he told BioWorld. “With that, we are very pleased.” Herceptin targets the outside of the receptor; Tukysa takes aim at the inside, and it’s that double-whammy that gets credit for the efficacy of the treatment, which also was generally well-tolerated.

The nod came as part of Project Orbis, under which the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (Switzerland) on the review. This is the first Project Orbis partnership among the FDA, HSA and Swissmedic; the application is still under review at the other agencies. Cooperation among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval, U.S. gatekeepers pointed out.

HER2Climb met the primary endpoint of progression-free survival (PFS), demonstrating that adding Tukysa brought an effect superior to Herceptin and capecitabine alone, with a 46% reduction in the risk of disease progression or death. Patients had previously tried Avastin, Perjeta (pertuzumab, Roche Holding AG) and Kadcyla (ado-trastuzumab emtansine, or T-DM1), and 47% showed brain metastases when they signed up.

The findings unveiled in October 2019 (hazard ratio ([HR]=0.54 (95% confidence interval [CI]: 0.42, 0.71); p<0.00001) came with news that the trial met the two key secondary endpoints at the interim analysis. The Tukysa arm showed an improvement in overall survival (OS), with a 34% reduction in the risk of death (HR=0.66 (95% CI: 0.50, 0.88); p=0.0048) compared to Avastin and capecitabine alone. For patients with brain involvement at baseline, the Tukysa arm also demonstrated superior PFS, with a 52% drop in the risk of disease progression or death compared to those who received only Avastin plus capecitabine alone (HR=0.48 (95% CI: 0.34, 0.69); p<0.00001). It was the first of many planned interim peeks at OS, and hitting the mark so early was cause for rejoicing. More data followed in December at the San Antonio Breast Cancer Symposium in Texas.

The U.S. wholesale acquisition cost, or WAC, for Tukysa is $18,500 for a 30-day supply, which is about $111,000 for an average course of treatment. Siegall said having biosimilars available to Herceptin means “a much more reasonable cost” of the regimen. “We believe we’ve priced this in a very fair way, based on its value.” Seagen now has three commercial drugs. Adcetris (brentuximab vedotin), a CD30-directed antibody-drug conjugate (ADC), gained its first U.S. approval in August 2011 for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Padcev (enfortumab vedotin-ejfv) is a Nectin-4 targeted ADC greenlighted late in 2019 for adults with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting.

Adcetris sold more than $1 billion for the first time last year. “With Padcev, we got approval right around Christmas, so we had January and February in the field “before sales efforts became virtual as a result of the COVID-19 pandemic, Siegall said. As a result of the virus, “we’ve had to create new methods for working and connecting with doctors. We’re doing a good job on it. A lot of doctors almost like this approach, rather than having a lot of salespeople in their office,” he added. “I don’t think it’s going to go away that fast” – at least not entirely – after COVID-19 is brought under control, since the digital or by-phone way “makes meeting with doctors efficient,” he said. Seagen’s first-quarter financial results are due at the end of this month.

Shares of Seagen (NASDAQ:SGEN) were trading at $136.87, up $3.47 cents.

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