On July 19, 2022 Novartis reported a solid second quarter (Press release, Novartis, JUL 19, 2022, View Source [SID1234616749]). Our six key in-market growth drivers with multi-billion sales potential (Cosentyx, Entresto, Zolgensma, Kisqali, Kesimpta, Leqvio) each grew at least double digits . The mid-stage pipeline remains on-track for 20+ potential significant pipeline assets with approval by 2026. Sandoz performance allows us to increase its guidance for the full-year and the strategic review is on track. Implementation of our streamlined organizational model is progressing well and is now expected to deliver approximately USD 1.5 billion in savings. We reconfirm our 2022 Group guidance and our confidence in delivering consistent growth and margin expansion."

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1 Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 47 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year. 2 A table showing the Q2 2022 and H1 2022 key figures excluding Roche can be found on page 9 and a reconciliation of 2021 IFRS results and non-IFRS measures core results to exclude the impacts of the 2021 divestment of our Roche investment can be found on page 55 of the Condensed Interim Financial Report. 3 Please see detailed guidance assumptions on page 7.

Strategy Update
Novartis is a focused medicines company, with depth in five core therapeutic areas (Hematology, Solid Tumors, Immunology, Neuroscience and Cardiovascular), strength in technology platforms (Gene Therapy, Cell Therapy, Radioligand Therapy, Targeted Protein Degradation and xRNA), and a balanced geographic footprint. Our confidence to grow in the near to mid-term is driven by potential multi-billion-dollar sales from our key growth brands: Cosentyx, Entresto, Kesimpta, Zolgensma, Kisqali and Leqvio. To fuel further growth through 2030 and beyond, we have 20+ assets with significant sales potential that could be approved by 2026.
Novartis remains disciplined and shareholder focused in our capital allocation. We balance investing in our business, through organic investments and value-creating bolt-ons, with returning capital to shareholders via our growing annual dividend and share buybacks. Our previously announced up to USD 15 billion share buyback is ongoing, with USD 9.4 billion still to be executed.
In April, we announced a streamlined organizational model, designed to support innovation, growth and productivity, the implementation of which is progressing well. With the changes, Novartis now expects to deliver SG&A savings of approximately USD 1.5 billion, to be fully embedded by 2024. The savings will contribute to achieving mid to long-term IM core margins in the low 40’s and investing in our pipeline.
The strategic review of Sandoz is on track; we expect to provide an update, at the latest, by the end of 2022.
Novartis continues to make significant strides in building trust with society and consistently integrating access strategies into how we research, develop and deliver our medicines. We are committed to net zero emissions across our value chain by 2040. During the quarter, our MSCI ESG rating was increased to "AA", placing us in the top quartile of companies within the pharmaceutical industry. Our culture journey towards an inspired, curious and unbossed organization continues, in order to drive performance and competitiveness in the long-term.

Financials
Second quarter
Net sales were USD 12.8 billion (-1%, +5% cc) in the second quarter, driven by volume growth of 12 percentage points, price erosion of 4 percentage points and the negative impact from generic competition of 3 percentage points.
Operating income was USD 2.2 billion (-36%, -30% cc), mainly due to lower product divestment gains (USD 0.4 billion), higher impairments (USD 0.4 billion) and higher restructuring costs (USD 0.3 billion) primarily related to the implementation of the new organizational model.
Net income was USD 1.7 billion (-41%, -34% cc), mainly due to lower operating income. Excluding the impact of Roche income, net income declined -29% (cc). EPS was USD 0.77 (-40%, -33% cc). Excluding the impact of Roche income, EPS declined -27% (cc).
Core operating income was USD 4.3 billion (-2%, +5% cc), mainly driven by higher sales, partly offset by higher R&D and M&S investments and lower gross margin. Core operating income margin was 33.4% of net sales, decreasing by 0.1 percentage points (+0.1 percentage points cc).
Core net income was USD 3.4 billion (-8%, -1% cc), as growth in core operating income was more than offset by the loss of Roche core income. Excluding the impact of Roche core income, core net income grew +8% (cc). Core EPS was USD 1.56 (-6%, +1% cc), benefiting from lower weighted average number of shares outstanding. Excluding the impact of Roche core income, core EPS grew +10% (cc).
Free cash flow amounted to USD 3.3 billion (-22% USD), compared to USD 4.2 billion in the prior year quarter, mainly due to lower divestment proceeds and unfavorable changes in working capital.

Innovative Medicines net sales were USD 10.5 billion (-1%, +5% cc) with volume contributing 13 percentage points to growth. Sales growth was mainly driven by continued strong performance from Entresto, Kesimpta, Cosentyx, Kisqali and Zolgensma. Generic competition had a negative impact of 4 percentage points, mainly due to Afinitor/Votubia, Gilenya (ex-US), Gleevec/Glivec, Exjade, and Sandostatin. Pricing had a negative impact of 4 percentage points. Sales in the US were USD 3.9 billion (+6%) and in the rest of the world USD 6.5 billion (-5%, +5% cc).
Sandoz net sales were USD 2.3 billion (-3%, +5% cc), benefiting from a return towards normal business dynamics, with growth across all business franchises. Volume contributed 11 percentage points to growth and pricing had a negative impact of 6 percentage points. Sales in Europe grew +4% (cc), while sales in the US declined -1%. Global sales of Biopharmaceuticals grew to USD 528 million (+1%, +11% cc).
First half
Net sales were USD 25.3 billion (+0%, +5% cc) in the first half, driven by volume growth of 12 percentage points, price erosion of 4 percentage points and the negative impact from generic competition of 3 percentage points.
Operating income was USD 5.1 billion (-14%, -7% cc), mainly due to lower product divestment gains (USD 0.4 billion), unfavorable fair value adjustments on financial assets (USD 0.2 billion) and higher restructuring costs (USD 0.2 billion) primarily related to the implementation of the new organizational model.
Net income was USD 3.9 billion (-21%, -14% cc), mainly due to lower operating income. Excluding the impact of Roche income, net income declined -4% (cc). EPS was USD 1.77 (-20%, -12% cc). Excluding the impact of Roche income, EPS declined -3% (cc).
Core operating income was USD 8.4 billion (+1%, +7% cc), mainly driven by higher sales, partly offset by higher R&D and M&S investments. Core operating income margin was 33.0% of net sales, increasing by 0.3 percentage points (+0.6 percentage points cc).
Core net income was USD 6.7 billion (-6%, +0% cc), as growth in core operating income was offset by the loss of Roche core income. Excluding the impact of Roche core income, core net income grew +9% (cc). Core EPS was USD 3.02 (-5%, +2% cc), benefiting from lower weighted average number of shares outstanding. Excluding the impact of Roche core income, core EPS grew +11% (cc).
Free cash flow amounted to USD 4.2 billion (-28% USD), compared to USD 5.8 billion in the prior year period, mainly due to lower divestment proceeds, unfavorable changes in working capital, and the loss of Roche annual dividend (prior year USD 0.5 billion), partly offset by favorable hedging results.
Innovative Medicines net sales were USD 20.6 billion (0%, +5% cc) with volume contributing 12 percentage points to growth. Sales growth was mainly driven by continued strong performance from Entresto, Kesimpta, Cosentyx, Kisqali and Zolgensma. Generic competition had a negative impact of 3 percentage points, mainly due to Afinitor/Votubia, Gleevec/Glivec, Exjade, Gilenya (ex-US) and Exforge. Pricing had a negative impact of 4 percentage points. Sales in the US were USD 7.6 billion (+4%) and in the rest of the world USD 13.1 billion (-3%, +5% cc).
Sandoz net sales were USD 4.7 billion (-1%, +6% cc), benefiting from a lower prior year comparison, which was most notable for the cough and cold season, as business dynamics continued to return towards normal. Volume contributed 13 percentage points and pricing had a negative impact of 7 percentage points. Sales in Europe grew +7% (cc), while sales in the US declined -2%. Global sales of Biopharmaceuticals grew to USD 1.0 billion (+1%, +9% cc).

Capital structure and net debt
Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns remains a priority.
During the first half of 2022, Novartis repurchased a total of 61.7 million shares for USD 5.4 billion on the SIX Swiss Exchange second trading line under the up-to USD 15 billion share buyback announced in December 2021. In addition, 1.2 million shares (for an equity value of USD 0.1 billion) were repurchased from employees. In the same period, 10.8 million shares (for an equity value of USD 0.5 billion) were delivered as a result of options exercised and share deliveries related to participation plans of employees. Novartis aims to offset the dilutive impact from equity based participation plans of employees over the remainder of the year. Consequently, the total number of shares outstanding decreased by 52.1 million versus December 31, 2021. These treasury share transactions resulted in an equity decrease of USD 5.0 billion and a net cash outflow of USD 5.2 billion.
As of June 30, 2022, net debt increased to USD 9.5 billion compared to USD 0.9 billion at December 31, 2021. The increase was mainly due to the USD 7.5 billion annual dividend payment and net cash outflow for treasury share transactions of USD 5.2 billion, partially offset by USD 4.2 billion free cash flow during the first half of 2022.
As of Q2 2022, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings.

Our guidance assumes that we see a continuing return to normal global healthcare systems, including prescription dynamics, and that no Gilenya and no Sandostatin LAR generics enter in the US.
In June 2022, an appeals court held the Gilenya US dosing regimen patent invalid. Novartis plans to petition the appeals court for further review to uphold validity of the dosing regimen patent. There is no generic competition in the US at this time. In Q2, Gilenya US sales were USD 332 million, US sales have been steadily declining due to competitive pressures.

Foreign exchange impact
If mid-July exchange rates prevail for the remainder of 2022, the foreign exchange impact for the year would be negative 6 to negative 7 percentage points on net sales and negative 7 to negative 8 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

On July 19, 2022 Johnson & Johnson (NYSE: JNJ) reported results for second-quarter 2022. "Our solid second quarter results across Johnson & Johnson reflect the strength and resilience of our Company’s market leadership in the midst of macroeconomic challenges," said Joaquin Duato, Chief Executive Officer (Press release, Johnson & Johnson, JUL 19, 2022, View Source [SID1234616748]). "I am continually energized by the focus and passion of my Johnson & Johnson colleagues and their dedication toward delivering transformative healthcare solutions to patients and consumers around the world."

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1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
4 Excludes intangible amortization expense and special items
Note: values may have been rounded

REGIONAL SALES RESULTS

1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
Note: Values may have been rounded

SEGMENT SALES RESULTS

1 Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2 Excludes the impact of translational currency
3 Excludes the net impact of acquisitions and divestitures and translational currency
4 Certain international OTC products, primarily in China, were reclassified from the Pharmaceutical segment to the Consumer Health segment based on operational changes
Note: Values may have been rounded

SECOND QUARTER 2022 SEGMENT COMMENTARY:

Adjusted operational sales* reflected below excludes the net impact of acquisitions and divestitures and translational currency.

Consumer Health

Consumer Health worldwide adjusted operational sales increased 2.9%*. Major contributors to growth include upper respiratory and analgesic products in the international market of our over-the-counter franchise as well as IMODIUM in digestive health products and NEUTROGENA in international Skin Health/Beauty.

Pharmaceutical

Pharmaceutical worldwide adjusted operational sales grew 12.4%*, driven by DARZALEX (daratumumab), a biologic for the treatment of multiple myeloma, STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, ERLEADA (apalutamide), a next-generation androgen receptor inhibitor for the treatment of patients with prostate cancer, TREMFYA (guselkumab), a biologic for the treatment of adults living with moderate to severe plaque psoriasis, and for adults with active psoriatic arthritis, and INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults. Also contributing to growth were sales of the Janssen COVID-19 Vaccine (Ad26.COV2.S) for the prevention of the SARS-CoV-2 virus. This growth was partially offset by declines in sales of REMICADE (infliximab), a biologic approved for the treatment of several immune-mediated inflammatory diseases and IMBRUVICA (ibrutinib), an oral, once daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer.

MedTech

MedTech worldwide adjusted operational sales grew 3.4%*, driven primarily by contact lenses and surgical vision products in our Vision franchise, and electrophysiology products in our Interventional Solutions business. Growth was partially offset by COVID-19 related mobility restrictions in certain regions.

NOTABLE NEW ANNOUCEMENTS IN THE QUARTER:

The information contained in this section should be read in conjunction with Johnson & Johnson’s other disclosures filed with the Securities and Exchange Commission, including its Current Reports on Form 8-K, Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. The reader is also encouraged to review all other news releases and information available in the Investors section of the company’s website at news releases, as well as www.factsabouttalc.com, www.factsaboutourprescriptionopioids.com, and www.LTLManagementInformation.com.

Regulatory Decisions

European Commission Grants Conditional Approval of CARVYKTI (ciltacabtagene autoleucel), Janssen’s First Cell Therapy, for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

(Press Release)

Janssen Announces U.S. FDA Breakthrough Therapy Designation Granted for Talquetamab for the Treatment of Relapsed or Refractory Multiple Myeloma

(Press Release)

Janssen Receives Positive CHMP Opinion for IMBRUVICA (ibrutinib) in a Fixed-Duration Combination Regimen for Adult Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL)

(Press Release)

Other

Johnson & Johnson Appoints Thibaut Mongon as CEO Designate of Planned New Consumer Health Company

(Press Release)

ETHICON Launches Next Generation ECHELON 3000 Stapler Designed for Exceptional Access and Control

(Press Release)

Johnson & Johnson Releases 2021 Health for Humanity Report Highlighting Performance on ESG Priorities and Progress Against Public Commitments

(Press Release)

New Data Show TREMFYA (guselkumab) Binds to Both Inflammatory Cells and Interleukin (IL)-23, Supporting a Hypothesis for a Differentiated Mechanism from Risankizumab

(Press Release)

Janssen to Highlight Science, Innovation and Advances in Robust Oncology Portfolio and Pipeline Through More Than 60 Data Presentations at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper)

FULL-YEAR 2022 GUIDANCE:

Johnson & Johnson does not provide GAAP financial measures on a forward-looking basis because the company is unable to predict with reasonable certainty the ultimate outcome of legal proceedings, unusual gains and losses, acquisition-related expenses and purchase accounting fair value adjustments without unreasonable effort. These items are uncertain, depend on various factors, and could be material to Johnson & Johnson’s results computed in accordance with GAAP.

($ in Billions, except EPS)

July 2022

1 Non-GAAP financial measure; excludes the net impact of acquisitions and divestitures
2 Non-GAAP financial measure; excludes the impact of translational currency
3 Calculated using Euro Average Rate: April 2022 = $1.09 and July 2022 = $1.05 (Illustrative purposes only)
4 Non-GAAP financial measure; excludes intangible amortization expense and special items
5 Excludes COVID-19 Vaccine
Note: percentages may have been rounded

Other modeling considerations will be provided on the webcast.

WEBCAST INFORMATION:

Johnson & Johnson will conduct a conference call with investors to discuss this earnings release today at 8:30 a.m., Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Johnson & Johnson website. A replay and podcast will be available approximately two hours after the live webcast in the Investors section of the company’s website at events-and-presentations.

On July 19, 2022 Genmab A/S (Nasdaq: GMAB) reported that worldwide net trade sales of DARZALEX (daratumumab), including sales of the subcutaneous (SC) formulation (daratumumab and hyaluronidase-fihj, sold under the tradename DARZALEX FASPRO in the U.S.), as reported by Johnson & Johnson were USD 1,986 million in the second quarter of 2022 (Press release, Genmab, JUL 19, 2022, View Source [SID1234616747]). Net trade sales were USD 1,021 million in the U.S. and USD 965 million in the rest of the world. Genmab receives royalties on the worldwide net sales of DARZALEX, both the intravenous and SC formulations, under the exclusive worldwide license to Janssen to develop, manufacture and commercialize daratumumab.

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On July 19, 2022 Bristol Myers Squibb (NYSE:BMY) reported that Rhumba Merger Sub Inc. ("Offeror"), a wholly owned subsidiary of Bristol Myers Squibb, has extended the expiration date of its offer (the "Offer") to acquire (the "Acquisition") all of the outstanding shares of common stock, par value $0.0001 per share ("Common Stock"), of Turning Point Therapeutics, Inc. (NASDAQ: TPTX), ("Turning Point") at a price of $76.00 per share, in cash, without interest, subject to any applicable withholding of taxes, pursuant to the terms of the Agreement and Plan of Merger, dated as of June 2, 2022, among Bristol Myers Squibb, Offeror and Turning Point (the "Merger Agreement") (Press release, Bristol-Myers Squibb, JUL 19, 2022, View Source [SID1234616746]). The Acquisition is expected to close during the third quarter of 2022.

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The Offer, which was previously scheduled to expire one minute following 11:59 p.m., Eastern Time, on July 18, 2022, has been extended until 5:00 p.m., Eastern Time, on August 15, 2022.

Equiniti Trust Company, the depositary for the Offer, has advised the Offeror that as of 5:30 p.m., Eastern Time, on July 18, 2022, 34,447,733 shares of Turning Point, representing approximately 69.0% of the issued and outstanding shares of Common Stock, have been validly tendered and not properly validly withdrawn pursuant to the Offer. Holders that have previously tendered their shares do not need to re-tender their shares or take any other action in response to this extension.

The Offer is being made pursuant to the terms and conditions described in the Offer to Purchase, dated June 17, 2022 (as it may be amended or supplemented from time to time, the "Offer to Purchase"), the related Letter of Transmittal and certain other offer documents, copies of which are attached to the Tender Offer Statement on Schedule TO (together with any amendments or supplements thereto, the "Tender Offer Statement") filed by Bristol Myers Squibb and Offeror with the U.S. Securities and Exchange Commission (the "SEC") on June 17, 2022, as amended.

The Offer is conditioned upon the fulfillment of certain conditions described in "The Offer—Section 15—Conditions to the Offer" of the Offer to Purchase, including, but not limited to, the termination or expiration of any applicable mandatory waiting period (and any extensions thereof) imposed under the Hart-Scott-Rodino Act.

On July 19, 2022 Daiichi Sankyo (TSE: 4568) and AstraZeneca reported that it’s (LSE/STO/Nasdaq: AZN) ENHERTU (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens (Press release, Daiichi Sankyo, JUL 19, 2022, View Source [SID1234616738]).

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ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The approval by the European Commission (EC) follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Breast03 phase 3 trial, which were published in The New England Journal of Medicine. In the DESTINY-Breast03 trial, ENHERTU reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.000001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) for patients treated with ENHERTU was not reached (95% CI: 18.5-NE) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2), as assessed by blinded independent central review (BICR).

In Europe, more than 530,000 patients are diagnosed with breast cancer each year.1 Approximately one in five patients with breast cancer are considered HER2 positive.2 Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4

"This approval is an important milestone for patients and clinicians in Europe, since previously treated patients with HER2 positive metastatic breast cancer typically experience disease progression in less than a year with historical standard of care treatment," said Javier Cortés, MD, PhD, Head, International Breast Cancer Center (IBCC), Barcelona, Spain. "In the DESTINY-Breast03 trial, the time to progression was extended well beyond a year for patients receiving ENHERTU, illustrating the potential for this medicine to set a new benchmark in the treatment of HER2 positive metastatic breast cancer."

Additional results from the DESTINY-Breast03 phase 3 trial showed that in the secondary endpoint of overall survival (OS), there was a strong trend towards improved OS with ENHERTU (HR=0.55; 95% CI: 0.36-0.86), however this analysis is not yet mature and further follow-up is ongoing. Nearly all patients treated with ENHERTU were alive at nine months (96.1%; 95% CI: 92.8-97.9) compared to 91.3% of patients treated with T-DM1 (95% CI: 87.1-94.2). Confirmed objective response rate (ORR) was more than doubled in the ENHERTU arm versus the T-DM1 arm (79.7% [n=208; 95% CI: 74.3-84.4] versus 34.2% [n=90; 95% CI: 28.5-40.3]).

The safety of ENHERTU has been evaluated in a pooled analysis of 573 patients across multiple tumor types who had received at least one dose of ENHERTU (5.4 mg/kg) in clinical studies. The median duration of treatment with ENHERTU was 11.3 months (range 0.7-37.9 months). The most common adverse reactions were nausea (77.0%), fatigue (57.2%), vomiting (46.8%), alopecia (38.0%), neutropenia (34.6%), constipation (33.9%), decreased appetite (33.7%), anemia (32.3%), diarrhea (30.7%), musculoskeletal pain (27.4%), transaminases increased (24.4%), leukopenia (24.1%), thrombocytopenia (23.0%), and upper respiratory tract infection (22.7%).

Cases of interstitial lung disease (ILD) or pneumonitis were reported in 12.0% of patients. Most ILD cases were grade 1 (2.6%) and grade 2 (7.3%). Grade 3 cases occurred in 0.7% of patients, no grade 4 cases occurred and grade 5 cases occurred in 1.4% of patients. Patients should be advised to immediately report cough, dyspnea (shortness of breath), fever and/or any new worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD or pneumonitis and those with suspected ILD or pneumonitis should be evaluated by radiographic imaging, preferably a computed tomography (CT) scan. Patients with a history of ILD or pneumonitis may be at increased risk.

"We believe there is a significant need to transform outcomes for patients with HER2 positive metastatic breast cancer in Europe," said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. "In DESTINY-Breast03, treatment with ENHERTU demonstrated superior progression-free survival and a doubling of the response rate compared to another HER2 directed ADC. With this approval we are now able to offer patients with HER2 positive metastatic breast cancer another option earlier in their treatment."

"With this approval, patients across Europe with HER2 positive metastatic breast cancer will have the opportunity to be treated with ENHERTU even earlier in the treatment of their disease, improving their chance for better outcomes beyond what we can already offer patients treated in later line settings," said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. "Today’s news is a further step in achieving our vision to continuously bring the transformative potential of ENHERTU to patients as early as possible in their treatment to improve cancer outcomes."

Based on the results of DESTINY-Breast03, the European Society for Medical Oncology Clinical Practice Guidelines were updated in October 2021 to recommend ENHERTU for use as the preferred second-line therapy for patients with HER2 positive metastatic breast cancer following progression with a taxane and trastuzumab.5

As part of this approval, the EC has also extended the market protection period for ENHERTU in this setting by one extra year based on the significant clinical benefit compared to existing approved therapies.

Financial Considerations

Following approval in the EU, an amount of $75 million is due from AstraZeneca to Daiichi Sankyo as a second-line milestone payment in HER2 positive metastatic breast cancer. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

About DESTINY-Breast03

DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Overall survival (OS) was a key secondary efficacy outcome measure. Secondary endpoints included ORR, duration of response and PFS based on investigator assessment. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Results from DESTINY-Breast03 have been published in The New England Journal of Medicine. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer

Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.6 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.6 In Europe, more than 530,000 patients are diagnosed with breast cancer each year.1 Approximately one in five patients with breast cancer are considered HER2 positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8

Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4

About ENHERTU

ENHERTU (trastuzumab deruxtecan, fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on the results from the DESTINY-Breast03 trial. ENHERTU also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

About the ENHERTU Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for ENHERTU are currently under review in China, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

ENHERTU is under review in Europe and Japan for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer must additionally have received or be ineligible for endocrine therapy.

ENHERTU also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 and DESTINY-Lung02 trials, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

ENHERTU recently was granted Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of the DESTINY-Breast04 trial. Patients with HR positive breast cancer should additionally have received or be ineligible for endocrine therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.