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FDA News Release

FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer

For Immediate Release:

Today, as part of Project Orbis, the U.S. Food and Drug Administration approved Tukysa (tucatinib) in combination with chemotherapy (trastuzumab and capecitabine) for the treatment of adult patients with advanced forms of HER2-positive breast cancer that can’t be removed with surgery, or has spread to other parts of the body, including the brain, and who have received one or more prior treatments.

The FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland) on this review. This is the first Project Orbis partnership between the FDA, HSA and Swissmedic. While the FDA approved Tukysa today, the application is still under review at the other agencies. Collaboration 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. Early availability of new therapies and adoption as standard of care around the world may have an impact on the increasingly international conduct of cancer clinical trials, potentially accelerating the development of anticancer products. With a framework for concurrent submission and review of oncology drugs, Project Orbis facilitates a collaborative review to identify any regulatory divergence across review teams.

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators. We are pleased to work with our Singapore and Switzerland colleagues for the first time, and to continue working alongside our Australian and Canadian colleagues as we facilitate new treatment options for patients – like today’s first new molecular entity under Project Orbis,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “This approval represents an additional targeted treatment option for patients with HER2-positive breast cancer. The clinical trial supporting this approval enrolled and specifically studied patients with active brain metastases in addition to the overall population enrolled, which also demonstrated benefit in this subgroup.”

HER2-positive breast cancer, which makes up approximately one-fifth of breast cancers, has too much of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. More than 25% of women with metastatic HER2-positive breast cancer will develop brain metastases.

“We recognize that patients with cancer constitute a vulnerable population at risk of contracting the coronavirus disease,” said Pazdur. “In this critical time, we remain steadfast in our commitment to patients with cancer and doing everything we can to expedite oncology product development. Tukysa was approved four months prior to the FDA goal date, providing an example of this commitment and showing how our regular work in reviewing treatments for patients with cancer is moving forward without delay.”

Tukysa is a kinase inhibitor meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Tukysa is approved for treatment after patients have taken one or more anti-HER2-based regimens in the metastatic setting. The FDA approved Tukysa based on the results of a clinical trial enrolling 612 patients who had HER2-positive advanced unresectable or metastatic breast cancer and had prior treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients with previously treated and stable brain metastases, as well as those with previously treated and growing or untreated brain metastases, were eligible for the clinical trial, and 48% of enrolled patients had brain metastases at the start of the trial.

The primary endpoint was progression-free survival (PFS), or the amount of time when there was no growth of the tumor. The median PFS in patients who received Tukysa, trastuzumab, and capecitabine was 7.8 months compared to 5.6 months in those patients who received placebo, trastuzumab, and capecitabine. Overall survival and PFS in patients with brain metastases at baseline were key secondary endpoints. The median overall survival in patients who received Tukysa, trastuzumab, and capecitabine was 21.9 months compared to 17.4 months in patients who received placebo, trastuzumab, and capecitabine. The median PFS in patients with brain metastases at baseline who received Tukysa, trastuzumab and capecitabine was 7.6 months compared to 5.4 months in patients who received placebo, trastuzumab and capecitabine.

Common side effects for patients taking Tukysa were diarrhea, palmar-plantar erythrodysesthesia (burning or tingling discomfort in the hands and feet), nausea, fatigue, hepatotoxicity (liver damage), vomiting, stomatitis (inflammation of the mouth and lips), decreased appetite, abdominal pain, headache, anemia and rash.

Tukysa can cause serious side effects including severe diarrhea associated with dehydration, acute kidney injury and death. Health care professionals should advise patients to notify their health care provider and start antidiarrheals as clinically indicated if diarrhea occurs. If patients are experiencing severe diarrhea, Tukysa should be interrupted or the dosage reduced. Tukysa can also cause severe hepatotoxicity. Health care professionals should monitor liver tests in patients taking Tukysa every three weeks while the patient is on treatment or as clinically indicated.

Women who are pregnant or breastfeeding should not take Tukysa because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to tell females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Tukysa and for at least one week after the last dose. The FDA also advises patients refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information.

In addition to the international collaboration with TGA, Health Canada, HSA Singapore and SMC Switzerland, this review used the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application. RTOR, as well as the Assessment Aid, facilitated discussions among the regulatory agencies and regulatory review.

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Tukysa was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need. Tukysa received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Tukysa to Seattle Genetics, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.


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Nathan Arnold

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