Medicines and Healthcare Products Regulatory Agency (MHRA) Authorises Seagen’s TUKYSA® (tucatinib) as Part of Combination Regimen for the Treatment of Adult Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

Medicines and Healthcare Products Regulatory Agency (MHRA) Authorises Seagen’s TUKYSA^® (tucatinib) as Part of Combination Regimen for the Treatment of Adult Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

- Authorised for Adult Patients with HER2-Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Anti-HER2 Treatment Regimens -

- Previously Designated as a Promising Innovative Medicine by MHRA -

- First HER-2 Tyrosine Kinase Inhibitor Combination Regimen to Improve Overall and Progression-Free Survival in Previously Treated Adult Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases -

LONDON – 22 Feb 2021 – Seagen UK Ltd. today announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation in Great Britain for TUKYSA^® (tucatinib) in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. The European centralised marketing authorisation granted by the European Commission for TUKYSA is valid in Northern Ireland. MHRA had previously granted TUKYSA a Promising Innovative Medicine (PIM) designation. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.[i],[ii]

“Every year, an estimated 55,000 people are diagnosed with breast cancer in the UK, of which up to one in five are estimated to have HER2-positive tumours,” said Dr. Alicia Okines, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust. “The authorisation of tucatinib in combination with trastuzumab and capecitabine is a significant step forward for adult patients with advanced, incurable HER2-positive breast cancer. With this authorisation, our patients, including those with disease that has spread to the brain, may have a new alternative therapeutic option that offers a meaningful survival benefit with a generally manageable side effect profile.”

“The TUKYSA combination is a landmark therapy for patients with HER2-positive metastatic breast cancer with or without brain metastases, extending overall survival in these patients after two prior anti-HER2-treatment regimens,” said Clay Siegall, Ph.D., Chief Executive Officer at Seagen. “We are pleased TUKYSA is now authorised in the UK, and we look forward to further collaborating with the national reimbursement bodies to ensure it is available to adult patients.”

The authorisation is based on results from the pivotal trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled, active comparator, global trial that 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 (T-DM1). 

HER2CLIMB Efficacy and Safety

The results for the primary endpoint showed patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (progression free survival (PFS)) compared to patients who received trastuzumab and capecitabine alone, with a median PFS of 7.8 months vs. 5.6 months respectively (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). A secondary endpoint showed that the addition of TUKYSA reduced the risk of death (overall survival (OS)) by 34 percent (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048), with a median OS of 21.9 months (95% CI: 18.3 to 31.0) vs. 17.4 months (95% CI: 13.6 to 19.9). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, nausea, vomiting, stomatitis, AST increase, ALT increase, and rash.¹

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2020, more than two million new cases of breast cancer were diagnosed worldwide, including 531,086 in Europe.[iii] Between 15 and 20 percent of breast cancer cases are HER2-positive.[iv] Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.^4,[v],[vi] Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.[vii]^,[viii],[ix]

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.

About Seagen

Seagen is a global biotechnology company that discovers, develops, and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland, and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

Forward-Looking Statements

Certain statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic potential of TUKYSA including its efficacy, safety and therapeutic uses, and the potential to make TUKYSA available to patients in the United Kingdom. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibilities that we may experience delays or setbacks in commercializing TUKYSA in the United Kingdom; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption “Risk Factors” included in the company’s Annual Report on Form 10-K for the year ended December 31, 2020 filed with the U.S. Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

[i] Medicines and Healthcare products Regulatory Agency. TUKYSA Summary of Product Characteristics.

[ii] Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models Mol Cancer Ther 2020;19:976-987.

[iii] Breast. Globocan 2020. World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf. Accessed January 28, 2021.

[iv] Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.

[v] Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.

[vi] Breast Cancer HER2 Status. American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed January 28, 2021.

[vii] Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.

[viii] Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.

[ix] Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.