Daiichi Sankyo and AstraZeneca’s Enhertu (trastuzumab deruxtecan), which is currently approved for the treatment of refractory, HER2-positive breast and gastric cancers, may soon be entering the treatment paradigm for HER2-mutant, non-small cell lung cancer (NSCLC). NSCLC is a highly lucrative disease setting, with GlobalData forecasting global Enhertu sales for this indication to exceed $365m by 2028.

Lung cancer is the second most common form of cancer, with NSCLC being its most prevalent subtype, accounting for 82% of new diagnoses. HER2 aberrations, including activating mutations, amplification events and protein overexpression, constitute a distinctive molecular biomarker for around 2–4% of NSCLC patients. These patients tend to be young, female and non-smokers who display a more aggressive phenotype, with frequent metastases, and poor survival outcomes. Despite anti-HER2 treatments being well-established for the treatment of breast and gastric cancers, existing HER2 tyrosine kinase inhibitors (TKIs) have had disappointing response rates amongst lung cancer patients and, to date, there are no approved HER2-directed therapeutics for the treatment of NSCLC.

In March 2019, Daiichi Sankyo and AstraZeneca entered a global partnership to jointly develop and commercialise Enhertu, an antibody-drug conjugate (ADC) consisting of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload. At an interim analysis of the Phase III DESTINY-Breast03 trial, the Independent Data Monitoring Committee declared that Enhertu has a ‘highly statistically significant and clinically meaningful benefit’ for the treatment of HER2-positive breast cancer compared to Roche’s competitor drug, Kadcyla. Key opinion leaders (KOLs) interviewed by GlobalData suggested possible causes for Enhertu’s superiority over Kadcyla, including a higher drug-to-antibody ratio and the ability to elicit a ‘bystander effect’, delivering the cytotoxic payload to neighbouring HER2-negative cancer cells.

The clinical efficacy of Enhertu for the treatment of lung cancer was tested in the pivotal Phase II trial DESTINY-Lung02, where it was administered to 91 patients with metastatic HER2-mutant NSCLC, refractory to standard treatment. The trial reported an objective response rate (ORR) of 55% and included one complete response. The median duration of response was 9.3 months, the median progression-free survival (PFS) was 8.2 months, and the median overall survival (OS) was 17.8 months.

Based on these results, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) to expand Enhertu’s indications to US patients with refractory, metastatic, HER2-mutant NSCLC. The application also received priority review status and, if approved, Enhertu may enter the NSCLC market by the third quarter of this year.

Having shown robust clinical efficacy and the highest response rate amongst existing HER2-directed therapies tested for NSCLC, GlobalData predicts Enhertu to monopolise this NSCLC therapeutic niche. A GlobalData analyst-consensus forecast projects the total annual sales for Enhertu across indications to reach $8bn by 2028, with a 2021–28 compound annual growth rate (CAGR) of 44.5%. The commercialisation programme for Enhertu includes expanding its use into HER2-positive urethral, endometrial and colorectal cancers and osteosarcoma settings. The use of Enhertu in combination with AstraZeneca’s anti-programmed death-ligand 1 (PD-L1), Imfinzi (durvalumab), is also being investigated, which could further increase revenue for AstraZeneca.

How well do you really know your competitors?

Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.

View profiles in store

Company Profile – free sample

Thank you!

Your download email will arrive shortly

Not ready to buy yet? Download a free sample

We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form

By GlobalData

Submit

UK USA Afghanistan Åland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos Islands Colombia Comoros Congo Democratic Republic of the Congo Cook Islands Costa Rica Côte d"Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati North Korea South Korea Kuwait Kyrgyzstan Lao Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, The Former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Micronesia Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Réunion Romania Russian Federation Rwanda Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and The Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and The South Sandwich Islands Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates US Minor Outlying Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam British Virgin Islands US Virgin Islands Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Kosovo

Industry * Academia & Education Aerospace, Defense & Security Agriculture Asset Management Automotive Banking & Payments Chemicals Construction Consumer Foodservice Government, trade bodies and NGOs Health & Fitness Hospitals & Healthcare HR, Staffing & Recruitment Insurance Investment Banking Legal Services Management Consulting Marketing & Advertising Media & Publishing Medical Devices Mining Oil & Gas Packaging Pharmaceuticals Power & Utilities Private Equity Real Estate Retail Sport Technology Telecom Transportation & Logistics Travel, Tourism & Hospitality Venture Capital

Tick here to opt out of curated industry news, reports, and event updates from Clinical Trials Arena.

Submit and download

Visit our Privacy Policy for more information about our services, how we may use, process and share your personal data, including information of your rights in respect of your personal data and how you can unsubscribe from future marketing communications. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address.

Figure 1 shows the forecast global sales of Enhertu until 2028 in the eight major markets, namely the US, France, Germany, Italy, Spain, the UK, Japan and China.