Innovative Medicines

is an oral signal transduction inhibitor of the BCR-ABL tyrosine kinase. Tasigna is approved in the US, the EU, Japan and other countries for the treatment of:

• Adults and children with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic and/or accelerated phase who are resistant or intolerant to existing treatment
• Newly diagnosed adults and children with Ph+ CML in the chronic phase

is an oral inhibitor of the mTOR pathway. Afinitor is approved in the US, the EU, Japan and other countries for oncology indications that vary by country. It is approved for the treatment of:

• Postmenopausal women with advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, in combination with the medicine exemestane, when certain other medicines have not worked
• Adults with renal cell carcinoma (advanced kidney cancer) when certain other medicines have not worked
• Adults with a type of cancer known as neuroendocrine tumor (NET) of the pancreas, and non-symptomatic NET of the stomach, intestine (gastrointestinal) or lung that has progressed and cannot be treated with surgery (Afinitor is not indicated for use in people with carcinoid tumors that actively produce hormones)

Everolimus is approved for additional indications as Afinitor/Afinitor Disperz in the US, Japan and other countries, and as Votubia (tablets and dispersible tablets) in the EU. The following indications vary by country:

• Adults with a kidney tumor called angiomyolipoma, which occurs with a genetic condition called tuberous sclerosis complex (TSC), when the tumor does not require immediate surgery (tablet formulation only)
• Adults and children who have TSC and a brain tumor called subependymal giant cell astrocytoma (SEGA) when the tumor cannot be removed completely by surgery
• Adults and children aged 2 years and older who have TSC and certain types of seizures (epilepsy), as an added treatment to other antiepileptic medicines (dispersible tablet formulation only)

Everolimus is available under the trade names Zortress/Certican for use in transplantation. It is exclusively licensed to Abbott Laboratories and sublicensed to Boston Scientific for use in drug‑eluting stents.

is an oral combination therapy. Tafinlar and Mekinist are kinase inhibitors of the BRAF and MEK1/2 proteins, respectively, approved in combination in the US, the EU, Japan and other countries for the treatment of:

• Adults with unresectable (not removable through surgery) or metastatic melanoma with a BRAF V600 mutation
• Adults with stage III melanoma with a BRAF V600 mutation as an adjuvant treatment
• Adults with advanced non-small cell lung cancer with a BRAF V600 mutation

Additionally, the combination is approved in the US and other countries for the treatment of:

• Adults with locally advanced or metastatic anaplastic thyroid cancer with a BRAF V600 mutation

Tafinlar and Mekinist are also indicated as single agents to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Novartis has worldwide exclusive rights to develop, manufacture and commercialize trametinib granted by Japan Tobacco Inc.

is an oral inhibitor of the JAK1 and JAK2 tyrosine kinases that is the first therapy approved in the EU, Japan and other countries to treat two kinds of myeloproliferative neoplasms, a group of related and rare blood cancers characterized by the overproduction of blood cells in the bone marrow. It is approved for the treatment of:

• Adults with myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis
• Adults with polycythemia vera who are resistant or intolerant to a medication called hydroxyurea

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization in the indications of oncology, hematology and graft-versus-host disease outside the US. Incyte Corporation markets ruxolitinib as JakafiR in the US.

is an oral tyrosine kinase inhibitor that targets a number of growth factors to limit new blood vessel and tumor growth. Votrient is approved in the US and Japan for the treatment of:

• Adults with advanced renal cell carcinoma (RCC)
• Adults with advanced soft tissue sarcoma (STS) who have received chemotherapy (it is not known if

Votrient is effective in treating adipocytic STS or certain gastrointestinal tumors)

Votrient is also approved in the EU for the treatment of:

• Adults with advanced RCC as first-line therapy, and adults with advanced RCC who have received cytokine therapy for advanced disease
• Adults with certain subtypes of advanced STS who have received chemotherapy for metastatic disease or whose cancer has progressed within 12 months after neoadjuvant therapy

is an intravenous radioligand therapyapproved in the US for the treatment of:

• Adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors

Lutathera is also approved in the EU and other countries for the treatment of:

• Adults with unresectable or metastatic, progressive, well-differentiated (G1 and G2), somatostatin receptor-positive GEP-NETs

is an oral kinase inhibitor. It is approved in the US and other countries for the treatment of:

• Postmenopausal women, and men, with HR+/HER2-advanced or metastatic breast cancer with a PIK3CA mutation, in combination with fulvestrant following disease progression on or after an endocrine-based regimen

Piqray received US approval in May 2019.

is a recombinant, humanized, high-affinity antibody fragment that binds to vascular endothelial growth factor A (VEGF‑A), a protein that causes the growth of blood vessels in the eye, which can lead to vision loss. Lucentis is an injectable anti‑VEGF therapy specifically designed for the eye, minimizing systemic exposure. It is approved in the EU, Japan and other countries. Approvals and indications vary by country:

• Adults with neovascular (wet) age‑related macular degeneration (AMD)
• Adults with visual impairment due to choroidal neovascularization (CNV)
• Adults with CNV secondary to pathologic myopia
• Adults with visual impairment due to diabetic macular edema
• Adults with visual impairment due to macular edema secondary to retinal vein occlusion (branch and central retinal vein occlusion)
• Adults with moderately severe to severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy
• Preterm infants with retinopathy of prematurity (ROP) in zone I (stage 1+, 2+, 3 or 3+) or zone II (stage 3+), or aggressive posterior ROP

Lucentis is licensed from Genentech, and Novartis holds the rights to commercialize the product outside the US. Genentech holds the rights to commercialize Lucentis in the US.

is an injectable, humanized single-chain antibody fragment that acts as an anti-VEGF agent. It is approved in the US for the treatment of:

• Patients with neovascular (wet) age-related macular degeneration

Beovu received US approval in October 2019.

is an injectable fully human monoclonal antibody that specifically inhibits interleukin-17A (IL‑17A), a cytokine involved in the pathogenesis of psoriasis, ankylosing spondylitis and psoriatic arthritis. It is approved in the US, the EU, Japan and other countries for the treatment of:

• Adults with moderate‑to‑severe plaque psoriasis
• Adults with active ankylosing spondylitis
• Adults with active psoriatic arthritis

Cosentyx is also approved in Japan for the treatment of:

• Adults with pustular psoriasis

is an oral sphingosine-1-phosphate (S1P) receptor modulator that has a reversible lymphocyte redistribution effect and readily crosses the blood-brain barrier to bind to the S1P receptors based in the central nervous system. It is approved in the US for the treatment of:

• Adults and children aged 10 years and older with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS)

Gilenya is also approved in the EU for the treatment of:

• Adults and children aged 10 years and older who have highly active RRMS despite treatment with at least one disease-modifying agent, or who have rapidly evolving severe RRMS

Gilenya is licensed from Mitsubishi Tanabe Pharma Corporation.

is a once-monthly injection that can be self-administered or administered by another trained person. It is specifically designed to block the calcitonin gene-related peptide receptor (CGRP-R), which plays a critical role in migraine. It is approved:

• In the US for the prevention of migraine in adults
• In the EU for the prevention of migraine in adults who have at least four migraine days per month

Aimovig is launched in 38 countries. Novartis and Amgen co-commercialize Aimovig in the US, where Amgen records sales. Novartis has exclusive commercialization rights for all ex-US territories, excluding Japan. The collaboration continues during the previously announced litigation between the companies and will remain in force until and unless a final court decision terminates the agreements.

is an injectable prescription medicine and the only approved antibody designed to target and block immunoglobulin E (IgE). It is approved in the US, the EU, Japan and other countries for the treatment of:

• Adults and children aged 6 years and older with moderate‑to‑severe, or severe, persistent allergic asthma
• Adults and children aged 12 years and older with chronic spontaneous urticaria/chronic idiopathic urticaria (hives)

Xolair is also approved in Japan for the treatment of:

• Patients with severe seasonal allergic rhinitis (hay fever)

Xolair is provided as lyophilized powder for reconstitution, and as liquid formulation in a pre‑filled syringe.

Novartis co-promotes Xolair with Genentech in the US and shares a portion of operating income, but Novartis does not record any US sales.

is an oral, first‑in‑class angiotensin receptor/neprilysin inhibitor. It enhances the protective neurohormonal systems of the heart (the neprilysin system) while simultaneously suppressing the harmful system (the renin‑angiotensin‑aldosterone system). Entresto is approved in the US, the EU and other countries for the treatment of:

• Adults who have symptomatic chronic heart failure with reduced ejection fraction (HFrEF)

Entresto is also approved in the US for the treatment of:

• Children aged 1 year and older who have symptomatic heart failure with systemic left ventricular systolic dysfunction 

Entresto is approved in 112 countries.

is an oral inhibitor of the DPP‑4 enzyme. It is approved in the EU, Japan and other countries for the treatment of:

• Adults with type 2 diabetes when used as monotherapy; in dual combination with metformin, a sulfonylurea or a thiazolidinedione; in triple combination with a sulfonylurea and metformin; and as an add-on to insulin (with or without metformin)

An oral single-pill combination of vildagliptin and metformin, marketed as Eucreas/EquMet/GalvusMet, is also approved in the EU, Japan and other countries for the treatment of type 2 diabetes. Sumitomo Dainippon Pharma Co. Ltd. promotes Equa and EquMet in Japan.

is an oral single‑pill combination of the ARB valsartan and the calcium channel blocker amlodipine besylate. It is approved in the US, the EU, Japan and other countries for the treatment of:

• Adults with hypertension

An oral single-pill combination of valsartan, amlodipine besylate and hydrochlorothiazide, marketed as Exforge HCT, is also approved in the US, the EU, Japan and other countries for the treatment of hypertension.

is an oral narrow-spectrum anthelmintic agent that inhibits a parasitic flatworm’s motility and interferes with the worm’s microtubular structure and function. Egaten is approved in the US, France and Egypt for the treatment of:

• Patients aged 6 years and older with fascioliasis, a parasitic infection commonly known as liver fluke Infestation

Egaten received US approval in February 2019. It is the only medicine for fascioliasis recommended by the World Health Organization (WHO) and is on the WHO Model List of Essential Medicines. Novartis has been donating Egaten to the WHO for the treatment of fascioliasis since 2005.

is an investigational oral BCR-ABL inhibitor that binds to the allosteric site of its target (BCR-ABL1). A broad clinical development program is investigating ABL001 as a monotherapy and as a combination therapy for the treatment of chronic myeloid leukemia (CML). This program includes the Phase III ASCEMBL third-line study, and the Phase II ASC-4MORE first-line study of ABL001 plus imatinib in patients with CML in chronic phase without achieving deep molecular response. Novartis is studying ABL001 in patients with and without genetic mutations that make them resistant to many targeted CML therapies.

is a gene therapy designed to address the genetic root cause of spinal muscular atrophy (SMA) by providing a functional copy of the human survival motor neuron (SMN) gene to halt disease progression through sustained SMN protein expression. The US Food and Drug Administration (FDA) approved the intravenous formulation of AVXS-101 as Zolgensma in May 2019 for the treatment of pediatric patients less than 2 years old who have SMA with biallelic mutations in the SMN1 gene. Regulatory reviews are underway in Europe, with a CHMP opinion anticipated in the first quarter of 2020, and in Japan, with a decision anticipated in the first half of 2020. AVXS-101 is in ongoing clinical studies, including the global Phase III STR1VE clinical program (consisting of STR1VE-US, STR1VE-EU and STR1VE-AP) to evaluate the intravenous formulation of AVXS-101 in patients who have SMA type 1, and the multinational Phase III SPR1NT trial in presymptomatic patients who have SMA with two or three copies of the SMN2 gene. Additionally, AVXS-101 intrathecal administration is being studied in a Phase I/II STRONG trial in patients who have SMA type 2 and three copies of the SMN2 gene. The STRONG trial is currently on partial clinical hold based on findings in a small preclinical animal study, and the Company is working with the FDA to determine next steps to resume dosing. New data from trials were presented at 2019 congresses, including the American Academy of Neurology Annual Meeting.

delivered subcutaneously as an injection, is a fully human, Fc-silenced IgG1 monoclonal antibody that blocks the CD40 receptor. CFZ533 is in clinical development to prevent graft rejection after organ transplantation and to treat several autoimmune diseases, including Sjogren’s syndrome. In the proof-of-concept study, CFZ533 demonstrated the ability to preserve graft function and pristine histology, confirming preclinical in vivo data. Recruitment is underway for two Phase II studies in kidney and liver transplant recipients (CIRRUS I and CONTRAIL I, respectively), and for a Phase II study in patients with Sjogren’s syndrome (TWINSS).

is an oral, first-in-class angiotensin receptor/neprilysin inhibitor. Novartis is
conducting multiple studies of sacubitril/valsartan as part of the FortiHFy clinical program, designed to generate additional data on sacubitril/valsartan and increase understanding of heart failure. The PIONEER-HF and TRANSITION studies both read out in 2018 and confirmed safety and superiority of Entresto versus enalapril in patients with chronic heart failure with reduced ejection fraction (HFrEF) who were stabilized following admission to the hospital for an acute decompensated heart failure event. The PROVE and EVALUATE trials read out in 2019. The PROVE-HF trial showed significant improvements in measures of cardiac structure and function at six months and one year in HFrEF patients; EVALUATE-HF results complemented PROVE-HF findings. The FortiHFy program also includes studies to investigate sacubitril/valsartan use in novel indications and expanded patient populations. These include PARAGON-HF and PARALLAX-HF, Phase III trials of sacubitril/valsartan in patients with chronic heart failure with preserved ejection fraction (HFpEF). Results of PARAGON-HF were published in September 2019, and while the trial narrowly missed its primary endpoint with a 13% treatment effect against an active valsartan comparator, the totality of evidence suggests that treatment with sacubitril/valsartan may result in clinically important benefits in HFpEF. US regulatory submission for HFpEF is on track for early 2020. PARALLAX-HF enrollment is complete and results are expected to be presented in 2020. Other trials include PARADISE-MI, a Phase III trial in patients at high risk of developing heart failure after a heart attack (post-acute myocardial infarction). Enrollment is ongoing and results are expected in 2020. Additionally, PARALLEL-HF is a Phase III trial for HFrEF patients in Japan (Novartis reported results in March 2019, and a marketing authorization submission in Japan is under review), and PANORAMA-HF is a Phase III trial in pediatric patients with heart failure (enrollment is ongoing and results are expected in 2021).

belongs to a novel class of antimalarial compounds called imidazolopiperazines. It has the potential to clear malaria infection, including resistant strains, and to block the transmission of the malaria parasite. As demonstrated in a Phase IIa proof-of-concept trial, the compound is fast-acting and potent across multiple stages of the parasite’s lifecycle, rapidly clearing both Plasmodium falciparum and Plasmodium vivax parasites. A Phase IIb study tested multiple dosing combinations and dosing schedules of KAF156 and lumefantrine in adults and adolescents, and confirmed good safety and efficacy of all doses. The safety and efficacy of the combination will now be evaluated in younger children.

is a long-acting, small-interfering RNA (siRNA) administered twice a year as a subcutaneous injection. It is in development in atherosclerotic cardiovascular disease and primary hyperlipidemia (including familial hypercholesterolemia) for patients who have already had an event like a heart attack or stroke, or who are risk-equivalent. Pivotal Phase III trial results were presented at the European Society of Cardiology Congress and the American Heart Association Scientific Sessions in 2019 by The Medicines Company, prior to its acquisition by Novartis. A cardiovascular outcomes study, ORION-4, is ongoing.

is an oral, highly potent and selective nonsteroidal multimodal farnesoid X receptor (FXR) agonist in development as both a monotherapy and a combination therapy for the treatment of nonalcoholic steatohepatitis (NASH). LJN452 is designed to target the three major facets of NASH (steatosis, inflammation and fibrosis), and has demonstrated the ability to reduce all three in animal models. Recruitment is complete for two Phase II studies: FLIGHT FXR (the monotherapy study) and TANDEM (the combination study with cenicriviroc). Additional collaborative studies are underway to explore the role of LJN452 as a backbone in combination therapies.

delivered as an intravenous infusion, is an investigational radioligand therapy in development for metastatic castration-resistant prostate cancer (mCRPC). Designed to target the prostate-specific membrane antigen present in most patients with mCRPC, 177Lu-PSMA-617 potentially offers a differentiated targeted treatment option. A Phase III study of 177Lu-PSMA-617 in patients with mCRPC, called VISION, is ongoing.

administered as a subcutaneous injection, is a fully human monoclonal antibody that works by binding to the CD20 molecule on the B-cell surface and inducing B-cell depletion. OMB157 is in development to treat multiple sclerosis (MS). Novartis announced in August 2019 that the Phase III ASCLEPIOS I and II studies met their primary endpoints in patients with relapsing forms of MS. Compared to AubagioR (teriflunomide), OMB157 showed a statistically significant reduction in the number of confirmed relapses, evaluated as the annualized relapse rate; highly significant suppression of both Gd+ T1 lesions and new or enlarging T2 lesions; and a relative risk reduction in three- and six-month confirmed disability worsening in pre-specified pooled analyses. Novartis is conducting a registration study for OMB157 in Japan, which started in March 2018.

is an investigational, novel, once- daily pill that blocks the DP2 pathway, a regulator of the inflammatory cascade. In December 2019, Novartis announced that development of QAW039 in asthma would be discontinued after the Phase III LUSTER-1 and LUSTER-2 core registration trials did not meet the clinically relevant threshold for reduction in asthma attacks (exacerbations) in moderate to severe patients with unresolved asthma despite treatment with inhaled therapies. In addition, as announced in October 2019, results of the Phase III ZEAL-1 and ZEAL-2 studies did not meet the primary efficacy endpoint of lung function (FEV1) improvement in patients with moderate asthma.

is an injectable, humanized, single-chain antibody fragment that acts as an anti-vascular endothelial growth factor (anti-VEGF) agent. The FDA approved RTH258 as Beovu in October 2019 for the treatment of neovascular (wet) age-related macular degeneration, and regulatory filings are under review in the EU, Japan and certain other countries. RTH258 is in clinical development for diabetic macular edema and retinal vein occlusion.

is an injectable antisense oligonucleotide designed to target elevated lipoprotein(a) (Lp(a)), which increases the risk of heart disease. The results of a Phase II trial announced in 2018 showed that TQJ230 reduced Lp(a) in patients by as much as 80%. The Lp(a) HORIZON trial, a Phase III trial in patients with established cardiovascular disease and elevated Lp(a), was initiated in December 2019. Results are expected in 2024. Novartis licensed TQJ230 from Akcea Therapeutics, Inc., an affiliate of Ionis Pharmaceuticals, Inc., in February 2019.

is a once-daily oral H4 receptor antagonist. It is in Phase II clinical development for the treatment of atopic dermatitis (AD) to evaluate its benefit on key outcomes, such as reduction of the severity of AD lesions and reduction of itch. The Phase II ZEST study is investigating the effect of several doses of ZPL389 versus placebo. ZPL389 has already demonstrated significant clinical and statistical improvements in eczema lesions, leading to a 50% reduction in Eczema Area and Severity Index (EASI) score compared to placebo after eight weeks of treatment, with a favorable safety profile in the proof-of-concept study.