Zolgensma

A separation of Sandoz via a 100 percent spin-off will create the leading European generics company and a global leader in biosimilars, and a more focused Novartis.

By Andrew Humphreys • [email protected]

 

Novartis

Lichtstrasse 35, CH-4056 

Basel, Switzerland
+41-61-324-1111 • novartis.com

 

Financial Performance
  2021 2020 1H 2022 1H 2021
Revenue $51,626 $48,659 $25,312 $25,367
Net income $24,018 $8,071 $3,914 $4,954
Diluted EPS $10.63 $3.52 $1.77 $2.20
R&D expense $9,540 $8,980 $4,818 $4,751
All figures are in millions of dollars, except EPS.

Best-selling products

All sales are in millions of dollars.

2021 sales

  • Cosentyx $4,718 
  • Entresto $3,548 
  • Gilenya $2,787 
  • Lucentis  $2,160 
  • Tasigna $2,060 
  • Promacta/Revolade $2,016 
  • Tafinlar + Mekinist $1,693 
  • Jakavi $1,595 
  • Xolair $1,428 
  • Sandostatin $1,413 
  • Zolgensma $1,351 
  • Galvus Group $1,092 
  • Ilaris $1,059 
  • Gleevec/Glivec $1,024 
  • Afinitor/Votubia $938 
  • Kisqali $937 
  • Exforge Group $901 
  • Diovan Group $773 
  • Kymriah $587 
  • Ultibro Group $584 
  • Votrient $577 
  • Exjade/Jadenu $563

1H 2022 sales

  • Cosentyx $2,434 
  • Entresto $2,218 
  • Gilenya $1,160 
  • Promacta/Revolade $1,025
  • Lucentis  $1,021 
  • Tasigna $959 
  • Tafinlar + Mekinist $855 
  • Jakavi $787 
  • Zolgensma $742 
  • Xolair $720 
  • Sandostatin $638 
  • Ilaris $560 
  • Kisqali $547 
  • Galvus Group $438 
  • Kesimpta $434 
  • Exforge Group $399 
  • Gleevec/Glivec $392 
  • Diovan Group $350 
  • Afinitor/Votubia $281 
  • Kymriah $263

Outcomes Creativity Index Score: 73

  • Manny Awards — 7
  • Cannes Lions — 4
  • Clio Health — 20
  • Creative Floor Awards — 25
  • London International Awards – N/A
  • MM+M Awards — 14
  • One Show — 3

 

Vas Narasimhan, Novartis

CEO Vas Narasimhan

Novartis announced in late August 2022 management’s intention to separate the generics and biosimilars division Sandoz into a new publicly traded standalone company, by way of a 100 percent spin-off. The spin-off aims to maximize shareholder value by creating the No. 1 European generics company and a worldwide leader in biosimilars, enabling Novartis shareholders to participate fully in the potential future upside for both Sandoz and Novartis Innovative Medicines.

For the Innovative Medicines and Sandoz businesses, the spin-off would allow for enhanced focus and management’s ability to pursue independent growth strategies. Sandoz is expected to deliver a new wave of growth based on the existing biosimilars pipeline of 15+ molecules, a strong and experienced managerial team and organization. Novartis intends to become a focused innovative medicines company with a stronger financial profile, and improved return on capital.

The standalone Sandoz would have headquarters based in Switzerland and be listed on the SIX Swiss Exchange, with an American Depositary Receipt (ADR) program in the United States.

According to Novartis Chair of the Board of Directors Joerg Reinhard, “Our strategic review examined all options for Sandoz and concluded that a 100 percent spin-off is in the best interest of shareholders. A spin-off would allow our shareholders to benefit from the potential future successes of a more focused Novartis and a standalone Sandoz, and would offer differentiated and clear investment theses for the individual businesses. Sandoz would become the publicly traded No. 1 European generics company and a global leader in biosimilars based in Switzerland.”

Novartis will continue expanding the company’s strong position in five core therapeutic fields (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. Additionally, Novartis will continue advancing the implementation of the company’s new organizational structure announced during April 2022, integrating the Pharmaceuticals and Oncology business units with separate U.S. and International commercial organizations supported by a new Strategy & Growth function and Operations unit to increase focus, strengthen competitiveness and drive synergies. The company remains dedicated to Novartis’ strong investment-grade credit rating and capital allocation priorities, including its growing (CHF) annual dividend.

Sandoz generated $9.6 billion in 2021 sales and served more than 100 markets with a strong presence in Europe as well as in the United States and Rest of World. The business would leverage its strong brand and sustain Sandoz’s leading worldwide position by continuing to invest in the key strategic areas of biosimilars, antibiotics, and generic medicines.

As a standalone company, Sandoz would focus on the vision to deliver patient access, leveraging the business’ strengths and purpose-driven workforce. Management says Sandoz would execute on a growth strategy with a focused approach to deploy resources efficiently and effectively, bolster key platforms and deliver launch excellence. Following the proposed spin-off, Sandoz would target an investment grade credit rating, providing sufficient financial flexibility to deliver on the business’ growth plans, invest in incremental growth opportunities, with a vision to deliver attractive dividends. Any Sandoz dividends would be incremental to Novartis dividends, the company said.

According to company management, “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 $15 billion share buyback is ongoing, with $9.4 billion still to be executed.”

During April 2022, Novartis 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 $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,” according to company executives.

Financial & Product performance

Novartis net sales during the first half of 2022 came to $25.31 billion (0 percent, +5 percent cc), 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. Net income fell year-over-year to $3.91 billion (-21 percent, -14 percent cc), mainly because of lower operating income. Excluding the impact of Roche income, net income fell 4 percent (cc). EPS amounted to $1.77 (-20 percent, -12 percent cc), and excluding the impact of Roche income, EPS decreased 3 percent (cc). During November 2021, Novartis agreed to sell 53.3 million (33 percent) Roche bearer shares in a bilateral transaction to Roche for a total consideration of $20.7 billion.  

Core net income was reported by Novartis at $6.7 billion (-6 percent, 0 percent 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 increased 9 percent (cc). Core EPS amounted to $3.02 (-5 percent, +2 percent cc), benefiting from lower weighted average number of shares outstanding. Excluding the impact of Roche core income, core EPS rose +11 percent (cc).

Innovative Medicines generated first-half 2022 net sales amounting to $20.6 billion (0 percent, +5 percent cc) with volume contributing 12 percentage points to growth. The company reported that generic competition had a negative impact of 3 percentage points, primarily due to Afinitor/Votubia, Gleevec/Glivec, Exjade, Gilenya (ex-US) and Exforge. Additionally, pricing had a negative impact of 4 percentage points. U.S. sales totaled $7.6 billion (+4 percent) and came to $13.1 billion (-3 percent, +5 percent cc) in the rest of the world during the first six months of 2022.

Sales growth in January–June 2022 was mainly driven by continued strong growth produced by Entresto ($2.22 billion, +32 percent, +37 percent cc), Kesimpta ($434 million, +274 percent, +280 percent cc), Cosentyx ($2.43 billion, +9 percent, +12 percent cc), Kisqali ($547 million, +30 percent, +36 percent cc), Zolgensma ($742 million, +17 percent, +22 percent cc), partly offset by generic competition primarily for Afinitor/Votubia, Gleevec/Glivec, Exjade and increased competition for Gilenya.

Entresto

The blockbuster medicine Entresto is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal, according to Novartis.

U.S. sales were primarily fueled by Entresto and Kesimpta, partly offset by the impact of generic competition mainly on Afinitor/Votubia and Gilenya because of increased competition. Sales growth in Europe ($7.0 billion, -6 percent, +4 percent cc) was led by Entresto and Jakavi, partly offset by Gilenya, due to increased competition. Emerging Growth Markets rose +4 percent (+10 percent cc), with China sales of $1.6 billion (+11 percent, +11 percent cc) driven by Cosentyx. 

Pacing Novartis’ sales product leaders during the first half of 2022 was Cosentyx, with continued demand-led growth in Europe and the United States, and accelerated growth in China. Since being initially approved during 2015, Cosentyx has a proven sustained efficacy profile across five systemic inflammatory conditions and has treated more than 700,000 patients around the globe.

Novartis’ other $2+ billion brand is Entresto (sacubitril/valsartan), which sustained
demand-led growth during first-half 2022 across all regions, with increased patient share across markets. In the United States, the medicine is indicated for heart failure patients with left ventricular ejection fraction (LVEF) below normal. In China, Entresto is included in the National Reimbursement Drug List for HFrEF and hypertension. In Japan, the drug is indicated for chronic heart failure and hypertension, and uptake is accelerating rapidly, according to Novartis. In the United States, the company is undergoing ANDA litigation with generic manufacturers.

Established Brands sales for Novartis during the 2022 first half reached decreased to $5.12 billion (-19 percent, -14 percent cc).

Sandoz net sales in first-half 2022 came in at $4.7 billion (-1 percent, +6 percent cc), benefiting from a lower previous-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, according to the company. Sales came to $2.5 billion (-4 percent, +7 percent cc) in Europe, $890 million (-2 percent) in the United States, $823 million (+2 percent, +8 percent cc) in Asia/Africa/Australasia and $500 million (+15 percent, +16 percent cc) in Canada and Latin America, driven by volume increases and tender wins.

Retail sales totaled $3.5 billion (0 percent, +7 percent cc), increasing across all regions. Total Anti-Infectives sales improved to $545 million (+5 percent, +11 percent cc) during January-June 2022.

Worldwide sales of Biopharmaceuticals (including contract manufacturing) increased to $1.0 billion (+1 percent, +9 percent cc), growing across most regions, and including +2 percentage points from a one-time contract manufacturing sale.

Zolgensma

The prescription gene therapy Zolgensma is used to treat children less than 2 years old with spinal muscular atrophy (SMA).

Commenting on Q2 2022, CEO Vas Narasimhan stated, “Novartis delivered a solid second quarter. 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 $1.5 billion in savings. We reconfirm our 2022 Group guidance and our confidence in delivering consistent growth and margin expansion.”

Sandoz guidance was revised upwards with sales anticipated to grow by low single digits and core operating income to be broadly in line with the previous year (revised upwards from to decline low-to-mid single digit).

For Innovative Medicines, full-year 2022 sales are expected to grow by mid single digits based on the company’s outlook as of August.

Novartis Group sales for 2022 are expected to grow by mid single digits, based on the full-year outlook. Core operating income was projected to grow by mid single digits.

“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 U.S.,” Novartis management said. “In June 2022, an appeals court held the Gilenya U.S. 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 U.S. at this time. In Q2, Gilenya U.S. sales were $332 million, U.S. sales have been steadily declining due to competitive pressures.”

Product Approvals & Pipeline Updates

The Novartis pipeline is one of the industry’s most innovative and inventive, with more than 160 projects undergoing clinical development. The portfolio consists of various blockbuster medicines being expanded with additional uses, new drug candidates, biosimilars, and more.

Kymriah (tisagenlecleucel) was cleared for U.S. and EU marketing in May 2022 for use in adults with relapsed or refractory (r/r) follicular lymphoma, after two or more lines of systemic therapy.

Novartis said in the final ELIANA analysis, 55 percent of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who were treated with Kymriah were still alive after more than five years. About 44 percent of patients who experienced remission within three months of infusion were still in remission at the five-year mark, showing the long-term benefit and curative potential of one-time Kymriah infusion. According to the company, the safety profile remained consistent with previously reported results, without late adverse effects in these heavily pretreated patients. The clinical data were displayed at the EHA2022 Congress.

Kymriah represents the first-ever FDA-approved CAR-T cell therapy. A one-time treatment designed to empower patients’ immune systems to fight their cancer, the prescription product is available for the treatment of r/r pediatric and young adult (up to and including 25 years of age) acute lymphoblastic leukemia (ALL), r/r adult diffuse large B-cell lymphoma (DLBCL) and r/r adult follicular lymphoma.

The FDA granted accelerated approval during June 2022 to Tafinlar + Mekinist as a treatment for adult and pediatric patients with unresectable or metastatic solid tumors that have a BRAF V600E mutation. The U.S. approval is supported by results from the Phase II ROAR and NCI-MATCH trials showing overall response rates up to 80 percent in patients with BRAF V600E solid tumors. 

On the clinical front, treatment with Taf + Mek resulted in 47 percent ORR compared to chemotherapy (11 percent) and reduced risk of progression or death by 69 percent, demonstrating significant efficacy improvement in patients aged 1 to 17 years old with BRAF V600 low-grade gliomas requiring first systemic treatment. The data were presented at ASCO 2022.

The combination of Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition research and patients reached according to Novartis, may help to slow tumor growth by blocking signals associated with the BRAF and MEK kinases that are implicated in the growth of various types of cancer. Tafinlar + Mekinist has been studied in more than 6,000 BRAF-positive patients in 20-plus ongoing and completed studies, including in pediatric patients 1 year of age and older, and has been prescribed to more than 200,000 patients globally.

The combination medicine is additionally approved for use in BRAF V600 mutation-positive unresectable or metastatic melanoma, as an adjuvant treatment for BRAF V600 mutation-positive melanoma after surgery, in BRAF V600 mutation-positive metastatic non-small cell lung cancer, and in BRAF V600 mutation-positive anaplastic thyroid cancer. 

The FDA approved Vijoice (alpelisib) during April 2022 as the first treatment for select patients with PIK3CA-Related Overgrowth Spectrum (PROS). This represents the only approved treatment to specifically address the root cause of PROS conditions in select patients 2 years of age and older. The marketing clearance is based on real-world data from the EPIK-P1 trial, which demonstrated patients treated with Vijoice experienced reduction in the size of PROS lesions and improvement of PROS-related signs and symptoms.

A kinase inhibitor, Vijoice treats rare overgrowth conditions caused by the effects of PIK3CA mutations in adults and children with PROS. The drug works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform. The United States marks the first approval worldwide for Vijoice.

Pluvicto (lutetium Lu 177 vipivotide tetraxetan, formerly referred to as 177Lu-PSMA-617) gained U.S. marketing clearance in March 2022 as the first targeted radioligand therapy for treating prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC). The U.S. regulatory agency additionally approved the complementary diagnostic imaging agent, Locametz, after radiolabeling with gallium-68 for the identification of PSMA-positive lesions.

FDA approval was based on the pivotal Phase III VISION study, where patients with pre-treated PSMA-positive mCRPC who received Pluvicto plus standard of care had a statistically significant reduction in risk of death; both alternate primary endpoints of overall survival and radiographic progression free survival were met. Two pivotal Phase III trials assessing Pluvicto in earlier lines of treatment for metastatic prostate cancer are under way, with a goal to move into earlier stages of disease.

The precision cancer treatment Pluvicto combines a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle). After administration into the bloodstream, the medicine binds to target cells, including prostate cancer cells that express the transmembrane protein PSMA. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells disrupting their ability to replicate and/or triggering cell death. Novartis has filed marketing authorization for Pluvicto to the European Medicines Agency (EMA) and other health regulators.

Cosentyx, Novartis

Novartis’ top-selling product Cosentyx is the first and only fully human biologic that directly inhibits interleukin-17A, an important cytokine involved in the inflammation of psoriatic arthritis (PsA), moderate-to-severe plaque psoriasis, ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).

The key growth brand Cosentyx (secukinumab) was approved in the European Union in June 2022 for use in the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in patients ≥6 years whose disease has responded inadequately to conventional therapy.

Meanwhile, Novartis announced in September 2022 the results from two pivotal, Phase III trials (SUNSHINE and SUNRISE), in which Cosentyx showed rapid and sustained relief from the common clinical signs and symptoms of moderate-
to-severe hidradenitis suppurativa (HS) with a favorable safety profile. The clinical data were shown as a late-breaking abstract at the 31st European Academy of Dermatology and Venereology (EADV) Congress.

Cosentyx is the first fully human biologic that directly inhibits interleukin-17A, a significant cytokine involved in the inflammation of psoriatic arthritis (PsA), moderate-to-severe plaque psoriasis, ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Cosentyx has been tested clinically for more than 14 years. Novartis says the medicine is backed by robust evidence, including five years of clinical data in adults supporting long-term safety and efficacy across moderate-to-
severe plaque psoriasis, PsA and AS2. According to the company, these data bolster the position of Cosentyx as a treatment across AS, nr-axSpA, PsA, moderate-to-severe plaque psoriasis (adult and pediatric) and two subtypes of JIA, ERA and JPsA. More than 700,000 patients have been treated with the drug across the globe since being launched during 2015. Cosentyx is approved for marketing in 100-plus countries.

Jakavi (ruxolitinib) was the recipient of EU approval in June 2022 as the first post-steroid treatment for acute and chronic graft-versus-host disease (GvHD). Jakavi represents the first JAK1/2 inhibitor available for patients in Europe who previously had no approved therapies for the treatment of steroid-refractory GvHD.

An oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases, Jakavi is approved by the European Commission for treating adults with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF, and additionally for patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies. Jakavi is approved in more than 100 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 85 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. Other regulatory filings are under way globally in MF and PV.

Ruxolitinib was licensed from Incyte for development and commercialization outside the United States. The drug is marketed in the United States by Incyte under the brand name Jakafi for adults with PV who have had an inadequate response to or are intolerant of hydroxyurea; for adults with intermediate or high-risk MF; for adult and pediatric patients 12 years and older with steroid-refractory acute GvHD; and adult and pediatric patients 12 years and older with chronic GvHD after failure of one or two lines of corticosteroids or other systemic therapy.

Tabrecta (capmatinib) garnered EU marketing clearance in June 2022 for the treatment of advanced non-small cell lung cancer (NSCLC), harboring alterations leading to METex14 skipping. The approval is based on the Phase II GEOMETRY mono-1 study, which demonstrated an overall response rate (ORR) of 51.6 percent in a cohort evaluating primarily second-line patients and 44 percent in all previously-treated patients with advanced NSCLC harboring alterations leading to METex14 skipping. Tabrecta is the No. 1 prescribed targeted therapy for advanced NSCLC with alterations leading to METex14 skipping worldwide.

Also approved in the United States, Switzerland, and Japan, Tabrecta is a kinase inhibitor that targets MET. The medicine was discovered by Incyte and licensed to Novartis during 2009. Incyte granted Novartis global exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Scemblix (asciminib) was approved by the European Commission (EC) near the end of August 2022 for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). According to the company, Scemblix is the first CML treatment in Europe that works by specifically targeting the ABL myristoyl pocket (also known as a STAMP inhibitor in scientific literature), offering a reimagined treatment approach for patients who experience intolerance and/or resistance to currently available TKI therapies.

In other Scemblix news, the product showed superior efficacy with more-than-two-fold improvement in major molecular response rate compared to Pfizer’s Bosulif (bosutinib) at 96 weeks (37.6 percent vs. 15.8 percent). Novartis said long-term safety remains consistent, with discontinuation rates due to adverse events more than three times lower in the Scemblix versus the Bosulif arm (7.7 percent vs. 26.3 percent). The clinical data were presented at the 2022 ASCO and EHA annual meetings.

The FDA granted accelerated approval of Scemblix during October 2021 for adults with Ph+ CML-CP, previously treated with two or more TKIs based on MMR rate at 24 weeks, and full approval for adult patients with Ph+ CML-CP with the T315I mutation. Novartis said in accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence. The longer-term, 96-week efficacy and safety data have been disclosed to the FDA and are under assessment via priority review.

Scemblix has also garnered marketing approval in Japan, Switzerland, and the United Kingdom for adults with Ph+ CML-CP with resistance or intolerance to at least two or more previous therapies.

Novartis reported results in September 2022 from a new pooled exploratory analysis across the entire MONALEESA Phase III program, confirming nearly one year of additional overall survival (OS) benefit in a subgroup of patients with aggressive forms of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2) advanced breast cancer (aBC). This subgroup analysis found that patients with visceral metastases – including liver metastases and multiple metastatic sites, which are typically associated with a poor prognosis – who were treated with Kisqali (ribociclib) plus endocrine therapy in the first-line setting, achieved a median OS of 62.7 months versus 52.1 months for those treated with endocrine therapy alone (HR=0.79;95 percent CI: 0.65-0.97). 

The European Commission approved Beovu (brolucizumab) 6 mg in March 2022 as a treatment for visual impairment due to diabetic macular edema (DME). This approval in DME marks the second indication for Beovu granted by the EC, which was initially cleared for the treatment of wet age-related macular degeneration (AMD) during 2020. The EC decision applies to all 27 EU member states as well as Iceland, Norway, and Liechtenstein.

Beovu (additionally known as RTH258) 6 mg is also approved for treating wet AMD in more than 70 countries, including in the United States, EU, UK, Japan, Canada, and Australia. Additional studies evaluating the effects of brolucizumab in patients with wet AMD, DME, and proliferative diabetic retinopathy (PDR) are under way.

New CDK4/6i data were presented at ASCO 2022 from the Phase 3 MONALEESA-2 study, reinforcing Kisqali as the only drug in its class with consistently proven overall survival benefit in HR+/HER2- advanced or metastatic breast cancer. Trial results showed Kisqali plus letrozole maintained an OS benefit for postmenopausal patients with HR+/HER2- metastatic breast cancer treated in the first line, including patients who required dose modification. 

Additionally, further follow-up of MONALEESA-3 demonstrated Kisqali plus fulvestrant achieved a median OS of more than five-and-a-half years (67.6 months) in the first-line setting for postmenopausal women living with HR+/HER2- advanced or metastatic breast cancer. The clinical data were showcased at European Society for Medical Oncology (ESMO) Breast Cancer Congress 2022.

Novartis said Kisqali is the only CDK4/6 inhibitor with proven overall survival benefit across all its three pivotal Phase III advanced breast cancer studies, and is recognized by the National Comprehensive Cancer Network (NCCN) guidelines as the only CDK4/6 inhibitor with overall survival benefit in first-line HR+/HER2- advanced breast cancer. Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line premenopausal patients with HR+/HER2- advanced breast cancer, according to the company. Also, Kisqali combined with either letrozole or fulvestrant has uniquely, among other CDK4/6i, received a score of four out of five for postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first line.

Kisqali has been cleared for approval in more than 95 countries, including by the FDA and the European Commission, for treating women with HR+/HER2- advanced or metastatic breast cancer in combination either with an aromatase inhibitor or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy. Kisqali in combination with fulvestrant is available as initial endocrine-based therapy or following disease progression on endocrine therapy in men in the United States.

Announced in June 2022, Kesimpta (ofatumumab) data from the Phase 3 ASCLEPIOS I/II studies and ALITHIOS open-label extension demonstrate that after four years nearly 8 out of 10 of people with relapsing multiple sclerosis (RMS) treated continuously with the medicine had no evidence of disease activity (NEDA-3), versus 5 out of 10 of those who switched to Kesimpta at a later date after initial teriflunomide treatment.

Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that provides the flexibility of self-administration for adults with RMS, according to Novartis. Kesimpta is an anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly injection, delivered subcutaneously. As demonstrated in preclinical studies, the medicine is believed to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion. The selective mechanism of action and subcutaneous administration enables precise delivery to the lymph nodes, where B-cell depletion in MS is necessary, and preclinical studies have demonstrated that it may preserve the B-cells in the spleen. Kesimpta’s once-per-month dosing differs from other anti-CD20 therapies as it allows faster repletion of B-cells, offering more flexibility in the management of MS. 

Ofatumumab was initially developed by Genmab and licensed to GlaxoSmithKline. Novartis gained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, during December 2015.

Ofatumumab has been approved for treating relapsing forms of multiple sclerosis in the United States, European Union, United Kingdom, Canada, China, Switzerland, Singapore, Australia, Japan, Argentina, United Arab Emirates, Albania, and India.

Nature Medicine published data for Zolgensma (onasemnogene abeparvovec) showing nearly all children with two and three copies of the SMN2 gene who were treated presymptomatically achieved age-
appropriate milestones, including sitting, standing and walking. According to the results, all children were free of respiratory and nutritional support, and serious, treatment-related adverse events.

Zolgensma is the only approved gene therapy for treating spinal muscular atrophy and the only SMA treatment designed to directly address the genetic root cause of the disease by replacing the function of the missing or non-working SMN1 gene to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion. Zolgensma has been cleared for marketing in more than 40 countries and more than 2,000 patients have been treated with Zolgensma worldwide across clinical studies, managed access programs, and in the commercial setting. 

Novartis Gene Therapies has an exclusive, global license with Nationwide Children’s Hospital to the intravenous and intrathecal delivery of AAV9 gene therapy for treating all types of SMA; has an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for the in vivo gene therapy treatment of SMA in humans; an exclusive, global licensing deal with Généthon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA; and a non-exclusive, worldwide license pact with AskBio for the use of its self- complementary DNA technology for SMA treatment.

Research shows that first-line tislelizumab combined with chemotherapy demonstrated median overall survival of 17.2 months versus 10.6 months for chemotherapy and reduced risk of death by 34 percent in patients with advanced esophageal squamous cell carcinoma. These results were presented at the 2022 ESMO World Congress on Gastrointestinal
Cancer.

Clinical data in collaboration with BeiGene from the Phase III RATIONALE 301 study demonstrated that tislelizumab showed non-inferior overall survival (OS) versus sorafenib (median OS: 15.9 months vs. 14.1 months; stratified HR=0.85 [95.003 percent CI: 0.712, 1.019]) in patients with previously untreated, unresectable hepatocellular carcinoma (HCC). The study met its primary objective of non-inferiority for OS; superiority was subsequently tested, which was not met.

Tislelizumab is a uniquely designed anti-PD-1 monoclonal antibody under review by the FDA and the EMA for advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior chemotherapy. The EMA is also reviewing tislelizumab for advanced or metastatic NSCLC after prior chemotherapy, and in combination with chemotherapy for previously untreated advanced or metastatic NSCLC.

Tislelizumab is being assessed within a global clinical development program consisting of 17 pivotal clinical studies across a wide array of solid tumors, with more than 9,000 patients enrolled in 35 countries and regions. Novartis is dedicated to advancing immuno-oncology (IO) therapies to increase the depth and durability of treatment response across more tumor types and to make transformational treatment improvements for more patients living with cancer.

Novartis has the rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan via a collaboration and license deal with BeiGene.

Biomarker analysis from the Phase 3 SOLAR-1 study demonstrated Piqray (alpelisib) plus fulvestrant has clinical benefit regardless of the presence of ESR1 mutations and genes implicated in CDK4/6 inhibitor resistance. Novartis presented the data at ASCO 2022.

The kinase inhibitor Piqray is developed for use in combination with fulvestrant for treating postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen. The prescription drug is approved in more than 70 countries, including the United States. In the European member states, Piqray plus fulvestrant is available after disease progression following endocrine therapy as monotherapy.

According to the company, Novartis is continuing to reimagine cancer with additional trials of Piqray. To complement the SOLAR-1 trial, the large Phase III study EPIK-B5, is being performed with Piqray in combination with fulvestrant following treatment with a CDK4/6 inhibitor and aromatase inhibitor. Novartis is additionally testing the potential of Piqray in triple-negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical study, in advanced HER2+ breast cancer in the EPIK-B2 Phase III trial and in ovarian cancer in the EPIK-O Phase III study.

For the new drug candidate sabatolimab, submission in MDS is anticipated to be based on the ongoing Phase III study as, in isolation, the Phase II STIMULUS-MDS-1 readout is not supportive of an early filing. 

In mid-August 2022, Novartis reported that the Phase III CANOPY-A trial testing adjuvant treatment with canakinumab (ACZ885), an inhibitor of interleukin-1beta (IL-1β), in adult patients with stages II-IIIA and IIIB (T>5cm N2) completely resected (R0) NSCLC did not meet its primary endpoint of disease-free survival (DFS) compared to placebo. According to the company, no unexpected safety signals were observed. 

Sandoz reported further progress on its biosimilar pipeline during September 2022, with the release of positive results from the integrated ROSALIA Phase I/III clinical study for the proposed biosimilar denosumab. The ROSALIA trial met the primary endpoints, confirming the proposed biosimilar denosumab matches the reference product in terms of pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity in postmenopausal women with osteoporosis.

In other biosimilar news, Sandoz announced in late July 2022 that the FDA had accepted the biologics license application (BLA) for the proposed first-of-a-kind biosimilar natalizumab. Developed by Polpharma Biologics, the application includes all indications covered by the reference medicine Tysabri for relapsing forms of multiple sclerosis (MS) including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), active secondary progressive disease in adults, and Crohn’s Disease. The EMA additionally accepted the marketing authorization application (MAA) for the proposed biosimilar natalizumab, as announced on July 15, covering treatment as a single disease-modifying therapy (DMT) in adults with highly active RRMS, the same indication as approved by the EMA for Tysabri.

The FDA also during July accepted for review Sandoz’s supplemental Biologics License Application (sBLA) for a high concentration formulation of 100 mg/mL (HCF) of the biosimilar Hyrimoz (adalimumab-adaz). The application includes the indications of the reference medicine and world’s top-selling Rx medicine Humira (adalimumab) not protected by orphan exclusivity, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Sandoz launched during April 2022 a generic brimonidine tartrate/timolol maleate eyedrop in the United States for patients with ocular hypertension, expanding its leading ophthalmic portfolio.

In February 2022, Sandoz introduced generic lenalidomide in 19 countries across Europe, expanding access to the essential oncology medication.

 Acquisitions, Deals & partnerships

Novartis announced in September 2022 an investment in next-generation biotherapeutics with the creation of a fully integrated, dedicated $300 million scientific environment. The investment will bolster the company’s capacity and capabilities for early technical development of biologics. Spanning both drug substance and drug product development, the multi-year investment will be implemented across existing Novartis locations in Switzerland, Slovenia, and Austria, strengthening the company’s ability to deliver on the increasing growth and diversity of Novartis’ early-stage biotherapeutics portfolio.

The company’s early-stage biologics portfolio has grown significantly in the last 15 years, according to Novartis. The portfolio has expanded beyond conventional monoclonal antibodies into a broad range of novel development candidates with the potential to be first-in-class, best-in-class or both, including antibody-drug conjugates and therapeutic proteins.

Management says this investment is intended to position Novartis at the forefront of biotherapeutic development, by supporting the company’s increasingly sophisticated pipeline with the most advanced technical infrastructure, alongside the highest level of capabilities. “It will create seamless, end-to-end development and manufacturing environments by embedding biologics development within existing Novartis commercial manufacturing facilities in Slovenia and Austria as well as by establishing a biologics hub on the Basel St. Johann Campus in Switzerland alongside the NIBR biologics center fostering scientific innovation, technology leadership and talent attraction. Collectively these commitments will enhance development processes targeting faster transition times from pre-clinical to first in human studies.”

Reto Fischer, head of the Technical Research Division, Global Drug Development, stated, “Across the industry, biotherapeutics account for almost one-half of all recent new drug approvals and have enormous potential to address unmet need across a wide range of diseases. We are building the scientific environment necessary to bring these complex biologic compounds from the bench through development in an integrated, seamless, and rapid fashion. In doing so, we are supporting our broader ambition to enable faster development and focused prioritization across our global portfolio.”