On April 23, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported that the European Commission (EC) has approved tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications, including first- and second-line use (Press release, BeiGene, APR 23, 2024, View Source [SID1234642245]).

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"Tislelizumab is foundational for BeiGene’s solid tumor portfolio and has demonstrated its potential across multiple tumor types, including NSCLC, in which there remains a significant unmet need at all stages of the disease," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "Today’s EC authorization marks the second in the region for tislelizumab, with both NSCLC and locally advanced or metastatic esophageal squamous cell carcinoma now approved in the European Union. Second-line use in ESCC was also approved just weeks ago by the U.S. Food and Drug Administration, putting us well on our way to fulfilling our commitment to bring this innovative therapy to many more patients around the world."

The approved indications for tislelizumab are:

In combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of adult patients with squamous NSCLC who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
In combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumors have PD-L1 expression on ≥50% of tumor cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
"Non-small cell lung cancer remains one of the most common and deadly cancers in Europe, with 50% of patients diagnosed already progressed to advanced stages, making it difficult to treat," said Luis Paz-Ares, M.D., Ph.D., Head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid. "Across three Phase 3 studies, tislelizumab has been shown to improve outcomes for patients with certain types of NSCLC, providing a new option for those facing the disease."

Tislelizumab was approved for these NSCLC indications under the brand name TIZVENI. BeiGene plans to combine the NSCLC indications with the second-line ESCC indication under the brand name TEVIMBRA, which will launch in the first EU countries later in 2024. TEVIMBRA is approved in the U.S. and EU for advanced or metastatic ESCC after prior chemotherapy and is under review by the European Medicines Agency and the U.S. Food and Drug Administration as a first-line treatment for patients with unresectable, recurrent, locally advanced or metastatic ESCC and for first-line gastric or gastroesophageal junction cancers.

The EC approval is based on the results from three Phase 3 studies in the RATIONALE program that enrolled 1,499 patients:

RATIONALE 307 (NCT03594747) is an open-label, randomized Phase 3 trial that enrolled 360 patients with advanced squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival (PFS), as well as higher objective response rates and a manageable safety/tolerability profile, regardless of PD-L1 expression. The most common grade ≥3 treatment emergent adverse events (TEAEs) were decreased neutrophil levels, neutropenia and leukopenia. See full study results published in JAMA Oncology.
RATIONALE 304 (NCT03663205) is an open-label, randomized Phase 3 trial that enrolled 334 patients with locally advanced or metastatic non-squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration. The most common grade ≥3 TEAEs were associated with chemotherapy and included neutropenia and leukopenia. See full study results published in the Journal of Thoracic Oncology.
RATIONALE 303 (NCT03358875) is an open-label, randomized Phase 3 trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of PD-L1 expression. The most commonly reported grade ≥3 TEAEs were pneumonia, anemia and dyspnea. See full study results published in the Journal of Thoracic Oncology.
BeiGene has launched more than 17 potentially registration-enabling trials with tislelizumab, of which 11 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, tislelizumab has demonstrated its potential to deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed tislelizumab globally to date.

About NSCLC

Lung cancer is the second most common type of cancer and the leading cause of cancer-related death worldwide.1 Lung cancer is the third most common cancer in Europe; NSCLC represents 85–90% of all lung cancers.2 In 2020, the number of new cases of lung cancer diagnosed in Europe was estimated at 477,534.3

About Tislelizumab

Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

Important Safety Information

The full European Summary of Product Characteristics (SmPC) for the NSCLC indications for tislelizumab, which includes safety data for NSCLC and ESCC, is available from the European Medicines Agency.

On April 23, 2024 Be Biopharma, Inc. ("Be Bio"), a company pioneering the development of engineered B Cell Medicines (BCMs), reported that it will present at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting being held May 7-11, 2024, in Baltimore, MD (Press release, Be Biopharma, APR 23, 2024, View Source [SID1234642243]).

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Details regarding the Be Biopharma presentation at the conference are as follows:

Title: CRISPR/Cas9-based precision B cell gene engineering coupled with artificial intelligence-guided protein design produces active and sustained levels of tissue nonspecific alkaline phosphatase for the treatment of Hypophosphatasia

Presenter: Monika Musial-Siwek, Ph.D., Director, Protein Sciences, Be Biopharma

Date: May 10, 2024

Time: 12:00 PM ET

Session Title: Friday Posters: Musculo-Skeletal Diseases
Session Room: Exhibit Hall
Final Abstract Number: 1649

The abstract highlights Be Bio’s novel approach using engineered B-cell Medicines (BCMs) as a potential new treatment for Hypophosphatasia (HPP), a genetic disorder characterized by loss-of-function mutations in the ALPL gene which impairs the mineralization of bones. Researchers used CRISPR/Cas9 precision gene engineering and artificial intelligence-guided protein design to modify primary human B cells to produce tissue nonspecific alkaline phosphatase (ALP), an enzyme deficient in people living with HPP. The nonclinical data demonstrates the engineered BCM successfully produces active ALP , highlighting the therapeutic potential of the BCM platform as a novel treatment modality for HPP. BCMs have key attributes of plasma cells, including natural longevity, high levels of protein secretion, the ability to engraft without host preconditioning, and the ability to be re-dosed, making them an attractive platform for sustained supply of biologics.

For more information, please visit the conference website View Source

About Engineered B Cell Medicines – A New Class of Cellular Medicines

The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.

On April 23, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported the European Commission (EC) has approved a label extension for XTANDI (enzalutamide) as monotherapy or in combination with androgen deprivation therapy (ADT) for the treatment of adult men with high-risk biochemical recurrent (BCR) non-metastatic hormone-sensitive prostate cancer (nmHSPC) who are unsuitable for salvage-radiotherapy (Press release, Astellas, APR 23, 2024, View Source [SID1234642242]).

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The extended approval for XTANDI is based on results from the Phase 3 EMBARK trial in 1,068 men with high-risk BCR nmHSPC, in whom levels of prostate-specific antigen (PSA), the biomarker which can be indicative of prostate cancer activity, doubled in nine months or less. The study showed patients treated with XTANDI in combination with leuprolide had a 57.6% lower chance of their cancer spreading or dying compared to those treated with leuprolide alone. Participants who were treated with XTANDI alone had a 36.9% reduction in risk.1

The European Association of Urology (EAU) revised their treatment guidelines in April 2024, recommending enzalutamide for men with high-risk BCR nmHSPC with or without ADT, after radiation therapy or surgery. Up until now, there has been no consensus on the standard of care for men in this setting.2

Dr. Antonio Alcaraz, Chairman of the Department of Urology at the University Hospital Clinic of Barcelona:
"When non-metastatic hormone-sensitive prostate cancer recurs and is allowed to evolve, it could potentially lead to metastasis. Facing a particularly high risk and poorer outcomes in this stage of prostate cancer are men with a rapidly rising PSA, where PSA levels double within 9 months. It is critical to manage the cancer carefully then, and I urge clinicians not to delay treatment in this setting. With this expanded approval for enzalutamide, clinicians now have an important new option to treat men with non-metastatic hormone-sensitive prostate cancer at high risk of metastasizing, which could become a new standard of care."

Ernst-Günther Carl, Chairman, Europa Uomo:
"There is a desperate need for additional effective treatment options for those living with advanced prostate cancer. Many men with hormone-sensitive prostate cancer undergo arduous surgery and rounds of radiotherapy, which can be a successful way to keep their cancer at bay. It is devastating then, when up to four in ten of those will go on to develop a recurrence that puts them at significantly greater risk of their cancer spreading and early death. The patient community welcomes any ongoing therapeutic research advances that may benefit those living with prostate cancer in progress."

Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Oncology Development, Astellas:
"This expanded approval for XTANDI is a vitally important advance for patients with nmHSPC with high-risk BCR and is a testament to our long and ongoing collaboration with a global network of dedicated clinical trial investigators, patient groups, clinical trial participants and their families. Efficacy and safety results from the EMBARK study demonstrate the potential for XTANDI as a new option for treatment in the early, recurrent hormone-sensitive prostate cancer setting. Astellas is in active discussions with regulatory authorities around the world to bring XTANDI to those who may benefit."

The EC approval follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in March 2024, recommending approval of XTANDI in the high risk BCR nmHSPC setting.3

XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with non-metastatic castration-sensitive prostate cancer (nmCSPC; also known as nmHSPC) with BCR at high risk for metastasis in November 2023.

Astellas will reflect the impact from this matter in its financial forecast of the fiscal year ending March 31, 2025 that is scheduled to be disclosed on April 25, 2024.

For more information, please see the press releases "Astellas Receives Positive CHMP Opinion for XTANDI in Additional Recurrent Early Prostate Cancer Treatment Setting" issued on March 25, 2024, and "European Medicines Agency Validates Type II Variation for Astellas’ XTANDI (enzalutamide) for Treatment of Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence" issued on September 12, 2023.

About EMBARK
The Astellas- and Pfizer-led Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with nonmetastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) with high-risk BCR at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients who were considered to experience high-risk BCR had a prostate-specific antigen doubling time (PSA-DT) ≤ 9 months; serum testosterone ≥ 150 ng/dL (5.2 nmol/L); and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer, or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide (n=355), enzalutamide 160 mg as a single agent (n=355), or placebo plus leuprolide (n=358). Leuprolide 22.5 mg was administered every 12 weeks.

EMBARK met its primary endpoint of metastasis-free survival (MFS) for the XTANDI plus leuprolide arm, demonstrating a statistically significant reduction in the risk of metastasis or death over placebo plus leuprolide. MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death due to any cause, whichever occurred first.

The study also met a key secondary endpoint, by demonstrating that patients treated with XTANDI (single agent) had a statistically significant reduction in the risk of metastasis or death versus placebo plus leuprolide, meeting its MFS endpoint.

In EMBARK, Grade 3 or higher adverse events (AEs) were reported in 46% of XTANDI plus leuprolide patients, 50% of patients treated with XTANDI (single agent), and 43% of patients receiving placebo plus leuprolide. Permanent discontinuation due to AEs as the primary reason was reported in 21% of XTANDI plus leuprolide patients, 18% in XTANDI (single agent) patients, and 10% in placebo plus leuprolide patients.

For more information on the EMBARK trial (NCT02319837) go to www.clinicaltrials.gov.

About High Risk Biochemical Recurrent Non-Metastatic Hormone Sensitive Prostate Cancer
In non-metastatic hormone (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC), no evidence of the cancer spreading to distant parts of the body (metastases) is detectable with conventional radiological methods (CT/MRI), and the cancer still responds to medical or surgical treatment designed to lower testosterone levels.4 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a BCR within 10 years.5 About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 will die as a result of their metastatic prostate cancer.6 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC and high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA-DT ≤ 9 months. High-risk BCR patients with a PSA-DT of ≤ 9 months have a higher risk of metastases and death.7

About XTANDI (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. Enzalutamide is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). Enzalutamide is currently approved for one or more of these indications in more than 90 countries, including in the United States, European Union and Japan. Over one million patients have been treated with enzalutamide globally.8

About XTANDI (enzalutamide) in the E.U.9
Enzalutamide is an androgen receptor signaling inhibitor indicated in the E.U.:

as monotherapy or in combination with androgen deprivation therapy for the treatment of adult men with high-risk biochemical recurrent (BCR) non-metastatic hormone-sensitive prostate cancer (nmHSPC) who are unsuitable for salvage-radiotherapy.
in combination with androgen deprivation therapy for the treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC).
for the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC).
for the treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
for the treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.
Important Safety Information
For Important Safety Information for enzalutamide please see the full Summary of Product Characteristics at: View Source

On April 23, 2024 Apmonia Therapeutics, a biopharmaceutical company developing innovative cancer therapies, reported that it has secured additional non-dilutive financing for a total of €2.7M (Press release, Apmonia Therapeutics, APR 23, 2024, View Source [SID1234642241]). This new financing is part of France 2030 investment plan. Apmonia Therapeutics is one of the winners of the 11th edition of the i-Nov Innovation Contest (operated by Bpifrance), and will receive the largest amount of funding (€2.2M) among the 42 prizewinners. Additional funding (€0.5M) will be
granted as part of the regionalized Plan d’Investissement d’Avenir (PIA4), co-financed by the Grand-Est Region and the French Ministry of the Economy, Finance and Sovereignty.

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Including previous fundraisings and financing already obtained, a total of €11M has been leveraged for the development of Apmonia Therapeutics’ technological platform.

A first clinical trial in patients with solid tumors, and a pioneering position in a new therapeutic class in oncology

Awarded a prize in the i-Nov competition, Apmonia Therapeutics’ INOTAX project aims to bring new therapeutic solutions to the medical need for solid tumor cancers. The company has identified and developed the first-in-class drug candidate TAX2, a peptide that acts as a modulator of the tumor
microenvironment by targeting the TSP-1/CD47 interaction.

At the same time, Apmonia Therapeutics’ scientific teams are working to develop new peptide-based therapies targeting the tumor microenvironment. Using advanced in silico technologies, the company
aims to identify new therapeutic targets and optimize the design of antagonistic peptides. This new financing will enable Apmonia Therapeutics to industrialize its drug discovery capabilities to accelerate
the development of new drug candidates.

"We are delighted to have won the i-Nov innovation contest, which testifies to the strong potential of our technological platform and our original approach", says Dr. Albin Jeanne, President of Apmonia Therapeutics, adding "This funding is a new milestone and a strong signal as Apmonia Therapeutics prepares to start its first clinical trial. It will also enable us to strengthen the development of our product pipeline, with potential applications in various pathologies".

"Bpifrance is proud to once again support one of France’s DeepTech nuggets, which has already been recognized on numerous occasions. Apmonia Therapeutics has an original technology and a management team whose expertise is widely recognized, and the funding granted today under both
the i-Nov innovation competition and the 4th Plan d’Investissement d’Avenir aims to foster the emergence of Apmonia Therapeutics as a leading company in its field, by supporting two strategic axes: clinical development prior to industrial and commercial launch, and portfolio diversification", explains
Lucie Jolibois, in charge of innovation at Bpifrance’s Champagne-Ardenne Regional Office.

On April 22, 2024 Novartis reported on Q1 2024 results and Vas Narasimhan, its CEO, said (Press release, Novartis, APR 23, 2024, View Source [SID1234642209]):
"Novartis continued its strong momentum with both sales growth and core margin expansion in Q1. Our performance was broad-based, across all key growth brands and geographies, allowing us to raise guidance for the full year 2024. We continued to advance our pipeline in Q1, with submission-enabling data for Scemblix first-line, Pluvicto pre-taxane and remibrutinib in CSU. The momentum in our business and pipeline gives us continued confidence in our mid- and long-term growth outlook."

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Key figures
Continuing operations3
Q1 2024 Q1 2023 % change
USD m USD m USD cc
Net sales 11 829 10 798 10 11
Operating income 3 373 2 618 29 39
Net income 2 688 2 150 25 37
EPS (USD) 1.31 1.02 28 41
Free cash flow 2 038 2 684 -24
Core operating income 4 537 3 906 16 22
Core net income 3 681 3 233 14 19
Core EPS (USD) 1.80 1.54 17 23
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 34 of the Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.
2. Please see detailed guidance assumptions on page 6.
3. As defined on page 26 of the Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business and the continuing corporate activities and Discontinued operations include operational results from the Sandoz business.

Strategy update
Our focus
In 2023, Novartis completed its transformation into a "pure-play" innovative medicines business. We have a clear focus on four core therapeutic areas (cardiovascular-renal-metabolic, immunology, neuroscience and oncology), with multiple significant in-market and pipeline assets in each of these areas, that address high disease burden and have substantial growth potential. In addition to two established technology platforms (chemistry and biotherapeutics), three emerging platforms (gene & cell therapy, radioligand therapy and xRNA) are being prioritized for continued investment into new R&D capabilities and manufacturing scale. Geographically, we are focused on growing in our priority geographies – the US, China, Germany and Japan.

Our priorities
Accelerate growth: Renewed attention to deliver high-value medicines (NMEs) and focus on launch excellence, with a rich pipeline across our core therapeutic areas.
Deliver returns: Continuing to embed operational excellence and deliver improved financials. Novartis remains disciplined and shareholder-focused in our approach to capital allocation, with substantial cash generation and a strong capital structure supporting continued flexibility.
Strengthening foundations: Unleashing the power of our people, scaling data science and technology and continuing to build trust with society.
Financials
Following the September 15, 2023, shareholder approval of the spin-off of Sandoz, Novartis reported its consolidated financial statements as "continuing operations" and "discontinued operations."

Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business and the continuing corporate activities. Discontinued operations include the Sandoz Division and selected portions of corporate activities attributable to Sandoz’s business, as well as certain expenses related to the spin-off.

While the commentary below focuses on continuing operations, we also provide information on discontinued operations.

Continuing operations
Net sales were USD 11.8 billion (+10%, +11% cc), with volume contributing 14 percentage points to growth. Generic competition had a negative impact of 2 percentage points and pricing had negative impact of 1 percentage point.

Operating income was USD 3.4 billion (+29%, +39% cc), mainly driven by higher net sales.

Net income was USD 2.7 billion (+25%, +37% cc), mainly driven by higher operating income. EPS was USD 1.31 (+28%, +41% cc), benefiting from the lower weighted average number of shares outstanding.

Core operating income was USD 4.5 billion (+16%, +22% cc), mainly driven by higher net sales. Core operating income margin was 38.4% of net sales, increasing 2.2 percentage points (+3.4 percentage points cc).

Core net income was USD 3.7 billion (+14%, +19% cc), mainly due to higher core operating income. Core EPS was USD 1.80 (+17%, +23% cc), benefiting from the lower weighted average number of shares outstanding.

Free cash flow from continuing operations amounted to USD 2.0 billion (-24% USD), compared with USD 2.7 billion in the prior-year quarter, due to a prior-year one-timer and timing of payments.

Discontinued operations
Discontinued operations in first quarter 2023 include the Sandoz generic pharmaceuticals and biosimilars division, certain corporate activities attributable to Sandoz and certain other expenses related to the spin-off of the Sandoz business.

As the Sandoz spin-off was completed on October 3, 2023, there were no operating results in the first quarter 2024 related to discontinued operations. In the first quarter 2023, discontinued operations net sales were USD 2.5 billion, operating income amounted to USD 238 million and net income from discontinued operations was USD 144 million. For further details see Note 3 "Significant transactions 2023 – Completion of the spin-off of the Sandoz business through a dividend in kind distribution to Novartis AG shareholders" and Note 12 "Discontinued operations" to the condensed interim consolidated financial statements.

Total Company
Total Company net income was USD 2.7 billion in 2024, compared to USD 2.3 billion in 2023 and basic EPS was USD 1.31 compared to USD 1.09 in prior year. Net cash flows from operating activities for total Company amounted to USD 2.3 billion and free cash flow amounted to USD 2.0 billion.

Q1 key growth drivers
Underpinning our financial results in the quarter is a continued focus on key growth drivers (ranked in order of contribution to Q1 growth) including:

Entresto (USD 1 879 million, +36% cc) sustained robust demand-led growth, with increased penetration in the US and Europe following continued adoption of guideline-directed medical therapy in heart failure, as well as in China with increased penetration in hypertension
Cosentyx (USD 1 326 million, +25% cc) sales grew mainly in the US, emerging growth markets and Europe, driven by recent launches (including HS and the IV formulation in the US) in addition to volume growth in core indications
Kesimpta (USD 637 million, +66% cc) sales grew across all regions reflecting increased demand for a high efficacy product with convenient self-administered dosing
Kisqali (USD 627 million, +54% cc) sales grew strongly across all regions, based on increasing recognition of consistently reported overall survival in HR+/HER2- advanced breast cancer
Pluvicto (USD 310 million, +47% cc) delivered sales growth in the US and Europe. With supply now unconstrained, the focus is on opening new sites and referral pathways, and initiating new patients
Leqvio (USD 151 million, +139% cc) continued to show steady growth, with a focus on patient on-boarding, removing access hurdles and enhancing medical education
Jakavi (USD 478 million, +18% cc) sales grew in Europe, emerging growth markets and Japan, driven by strong demand in both myelofibrosis and polycythemia vera
Scemblix (USD 136 million, +83% cc) sales grew across all regions, demonstrating the high unmet need in later lines of CML
Xolair (USD 399 million, +15% cc) sales grew across all regions
Ilaris (USD 356 million, +14% cc) sales grew across all regions, led by the US and Europe
Sandostatin Group (USD 355 million, +9% cc) sales grew mainly in the US
Tafinlar + Mekinist (USD 474 million, +5% cc) sales grew in emerging growth markets and Japan, partly offset by a decline in the US
Lutathera (USD 169 million, +14% cc) sales grew across all regions due to increased demand
Emerging Growth Markets* Grew +21% (cc) overall. China grew 31% (cc) to USD 1.0 billion, mainly driven by Entresto and Cosentyx
*All markets except the US, Canada, Western Europe, Japan, Australia, and New Zealand

Net sales of the top 20 brands in Q1 2024
Q1 2024 % change
USD m USD cc
Entresto 1 879 34 36
Cosentyx 1 326 23 25
Kesimpta 637 66 66
Kisqali 627 51 54
Promacta/Revolade 520 -5 -4
Jakavi 478 15 18
Tafinlar+Mekinist 474 3 5
Xolair 399 13 15
Tasigna 395 -15 -13
Ilaris 356 9 14
Sandostatin Group 355 8 9
Lucentis 314 -25 -23
Pluvicto 310 47 47
Zolgensma 295 -5 -3
Exforge Group 192 3 5
Gilenya 175 -25 -24
Lutathera 169 13 14
Leqvio 151 136 139
Galvus Group 149 -19 -12
Diovan Group 140 -11 -7
Top 20 brands total 9 341 16 18
R&D update – key developments from the first quarter
New approvals
Xolair
(omalizumab) FDA approval of Xolair for the reduction of allergic reactions, including anaphylaxis, that may occur with accidental exposure to one or more foods in adult and pediatric patients aged 1 year and older with IgE-mediated food allergy
Regulatory updates
Fabhalta
(iptacopan) Positive CHMP opinion received for Fabhalta for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) patients

FDA filing accepted for the treatment of adult patients with IgA nephropathy (IgAN), and priority review granted
Results from ongoing trials and other highlights

Scemblix
(asciminib) Phase III ASC4FIRST study met both primary endpoints (major molecular response rate vs imatinib and vs investigator-selected tyrosine kinase inhibitors) with clinically meaningful and statistically significant results in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Additionally, Scemblix showed a favorable safety and tolerability profile. Data will be presented at upcoming medical conferences and submitted to regulatory authorities in 2024
Fabhalta
(iptacopan)

Phase III APPLAUSE-IgAN data showed a clinically meaningful and statistically significant proteinuria reduction of 38.3% vs placebo for patients with IgA nephropathy (IgAN). Fabhalta was well tolerated with a favorable safety profile consistent with previously reported data. Data presented at WCN 2024

In addition, extension data from the Phase III APPLY-PNH and APPOINT-PNH studies were presented at EBMT 2024, demonstrating the sustained long-term efficacy and safety profile of Fabhalta in PNH patients
Pluvicto In the Phase III PSMAfore study, updated OS results from a pre-planned analysis at approximately 75% information fraction demonstrated an OS HR<1.0 in the intent-to-treat population unadjusted for cross-over. Novartis is on track to file for the Pluvicto pre-taxane label expansion in H2 2024
Remibrutinib 52-week data from the Phase III REMIX-1 and REMIX-2 studies showed consistent efficacy of remibrutinib in CSU as early as week 2 and sustained up to 1 year. Remibrutinib was well tolerated and demonstrated a consistent, favorable long-term safety profile. Overall rates of AEs in remibrutinib arms were comparable to placebo with balanced liver function tests across both studies. Full data will be presented at an upcoming medical meeting. Novartis plans to submit remibrutinib for regulatory approval in H2 2024

In addition, a Phase II trial in hidradenitis suppurativa demonstrated that remibrutinib (both doses) met the primary endpoint with patients reporting a greater rate of simplified HiSCR at week 16 compared with placebo. Data presented at AAD 2024
Lutathera

Phase III NETTER-2 trial demonstrated that Lutathera plus octreotide LAR significantly extended median PFS to 22.8 months vs 8.5 months with high-dose octreotide LAR alone in patients with newly diagnosed grade 2 and 3 advanced GEP-NETs. No new or unexpected safety findings were observed. Data presented at ASCO (Free ASCO Whitepaper)-GI 2024
Leqvio

New data demonstrating the early addition of Leqvio to maximally tolerated statin therapy in a real-world setting significantly reduced LDL-C in ASCVD patients, including those with a history of an ASCVD-related event, who could not reach their goal on statin therapy alone. Data presented at ACC 2024 and published in the Journal of the American College of Cardiology
Kesimpta ALITHIOS open-label extension study showed sustained efficacy of first-line, continuous Kesimpta treatment up to six years in recently diagnosed treatment-naïve RMS patients, including 44% fewer relapses vs those who switched later to Kesimpta from teriflunomide. Kesimpta treatment was also well-tolerated with a consistent safety profile across the ALITHIOS population. Data presented at AAN 2024
Kisqali Results of the Phase III NATALEE study were published in the New England Journal of Medicine. In the trial, ribociclib plus endocrine therapy (ET) compared to ET alone significantly reduced the risk of recurrence by 25% across a broad population of patients with stage II and III HR+/HER2- early breast cancer, including those with no lymph node involvement
Zolgensma Final data from Phase IIIb SMART study supports use of Zolgensma in older and heavier SMA patients (1.5-9.1 years of age and weighing ≥8.5kg to ≤21kg) than the children treated in previous clinical studies. Nearly all treated patients maintained or improved motor milestones after 52 weeks, with most switching to the one-time gene therapy from chronically administered disease-modifying therapy. Data presented at MDA 2024
BD&L Announced the planned acquisition of MorphoSys, including pelabresib (late-stage BET inhibitor for myelofibrosis) and tulmimetostat (early-stage dual EZH2 and EZH1 inhibitor for solid tumors or lymphomas). The transaction aligns with Novartis strategic focus on oncology and strengthens our efforts in developing next-generation treatment options for cancer. Transaction is expected to close in Q2 2024

Novartis has exercised its exclusive option to acquire IFM Due. The acquisition gives Novartis full rights to IFM Due’s portfolio of STING antagonists, strengthening the company’s inflammatory diseases pipeline and building on our efforts to innovate new treatments for inflammation-driven conditions.

Novartis entered into a transaction with Arvinas including an exclusive strategic license agreement for the worldwide development and commercialization of ARV-766, a second generation PROTAC androgen receptor (AR) degrader, complementing our radioligand therapy platform in prostate cancer.
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.

In Q1 2024, Novartis repurchased a total of 10.3 million shares for USD 1.0 billion on the SIX Swiss Exchange second trading line under the up-to USD 15 billion share buyback announced in July 2023 (with up to USD 11.7 billion still to be executed). In addition, 1.0 million shares (for an equity value of USD 0.1 billion) were repurchased from associates. In the same period, 7.7 million shares (for an equity value of USD 0.3 billion) were delivered as a result of share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 3.6 million versus December 31, 2023. These treasury share transactions resulted in an equity decrease of USD 0.9 billion and a cash outflow of USD 1.1 billion.

As of March 31, 2024, net debt increased to USD 15.8 billion compared to USD 10.2 billion net debt at December 31, 2023. The increase was mainly due to the USD 5.2 billion annual net dividend payment in March (which is the gross dividend of USD 7.6 billion reduced by the USD 2.4 billion Swiss withholding tax that was paid in April 2024, according to its due date), cash outflow for treasury share transactions of USD 1.1 billion and net cash outflow for M&A / intangible assets transactions of USD 1.2 billion, partially offset by USD 2.0 billion free cash flow.

As of Q1 2024, the long-term credit rating for the company is Aa3 with Moody’s Ratings and AA- with S&P Global Ratings.

2024 outlook
Barring unforeseen events; growth vs prior year in cc Previous guidance
Net sales Expected to grow high single to low double-digit (from mid-single-digit)
Core operating income Expected to grow low double-digit to mid-teens (from high single-digit)
Key assumptions:

Our guidance assumes that no Entresto generics and no Promacta generics launch in the US in 2024
Foreign exchange impact
If late-April exchange rates prevail for the remainder of 2024, the foreign exchange impact for the year would be negative 2 percentage points on net sales and negative 4 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.

Novartis proposes Dr. Giovanni Caforio as Chair of the Board of Directors at the AGM in 2025
The 12-year term of Dr. Joerg Reinhardt as Chair of the Board of Directors ends as scheduled in 2025, when he will retire and not be available for re-election at the Annual General Meeting. Dr. Reinhardt joined Sandoz in 1982 and has held managerial positions with increasing responsibility in Sandoz and thereafter Novartis, including Head of the Vaccines and Diagnostics Division and Chief Operating Officer. In 2013, he was appointed Chair of the Board of Directors. During his leadership, Novartis transformed from a diversified healthcare enterprise to a focused medicines company.

The Board of Directors is proposing the nomination of Dr. Giovanni Caforio as Chair of the Board of Directors. Shareholders will vote on Dr. Caforio’s nomination to the Board at the next AGM 2025.

Since joining Bristol Myers Squibb in 2000, Dr. Caforio has served in various senior roles at the company. From May 2015 to November 2023, Dr. Caforio was CEO and from May 2017 to March 2024, he served as Executive Chairman. Under his leadership, BMS successfully transformed into a global medicines company with strong capabilities across R&D and commercialization. Dr. Caforio was born and educated in Italy and holds Italian and US citizenship. He is a physician by training and received his M.D. from the University of Rome. Dr. Caforio is fluent in Italian, French, Spanish, Portuguese and English.

Key figures1

Continuing operations2 Q1 2024 Q1 2023 % change
USD m USD m USD cc
Net sales 11 829 10 798 10 11
Operating income 3 373 2 618 29 39
As a % of sales 28.5 24.2
Net income 2 688 2 150 25 37
EPS (USD) 1.31 1.02 28 41
Cash flows from operating activities 2 265 2 852 -21
Non-IFRS measures
Free cash flow 2 038 2 684 -24
Core operating income 4 537 3 906 16 22
As a % of sales 38.4 36.2
Core net income 3 681 3 233 14 19
Core EPS (USD) 1.80 1.54 17 23


Discontinued operations2 Q1 2024 Q1 2023 % change
USD m USD m USD cc
Net sales 2 503 nm nm
Operating income 238 nm nm
As a % of sales 9.5
Net income 144 nm nm
Non-IFRS measures
Core operating income 507 nm nm
As a % of sales 20.3


Total Company Q1 2024 Q1 2023 % change
USD m USD m USD cc
Net income 2 688 2 294 nm nm
EPS (USD) 1.31 1.09 nm nm
Cash flows from
operating activities 2 265 2 957 nm nm
Non-IFRS measures
Free cash flow 2 038 2 720 nm nm
Core net income 3 681 3 614 nm nm
Core EPS (USD) 1.80 1.71 nm nm
nm=not meaningful

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 34 of the Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.
2. As defined on page 26 of the Interim Financial Report, Continuing operations include the retained business activities of Novartis, comprising the innovative medicines business and the continuing corporate activities and Discontinued operations include operational results from the Sandoz business.

Detailed financial results accompanying this press release are included in the Interim Financial Report at the link below:
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