A recent analysis from Clarivate Analytics’ Cortellis identifies 11 drugs that are expected to enter the market in 2020 and achieve blockbuster status by 2024. Which drugs are making the mark?

Blockbuster watch: Big Pharma

A recent analysis by Clarivate Analytics’ Cortellis Forecast Team identifies 11 medicines that are projected to enter the market in 2020 and reach blockbuster status (sales of $1 billion or more) by 2024 (see Table I at end of article).

Among the large pharma companies, Bristol-Myers Squibb (BMS), through its $74-million acquisition of Celgene, and Novartis each have two projected blockbusters slated to enter the market in 2020. For BMS, its two potential blockbusters are: ozanimod, an immunomodulatory drug for treating relapsing forms of multiple sclerosis (MS), and lisocabtagene maraleucel (liso-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T‑cell immunotherapy for treating relapsed or refractory large B-cell lymphoma after at least two prior therapies. Novartis potentially scores with two medicines: ofatumumab (subcutaneous) for treating relapsing forms of multiple sclerosis (MS), and inclisiran, which Novartis acquired in its $9.7-billion acquisition of The Medicines Company last month (January 2020), for treating hypercholesterolemia.

Gilead Sciences, Novo Nordisk, AstraZeneca/Daiichi Sanyko, and Mitsubishi Tanabe Pharma/Otsuka Pharmaceutical each have one drug slated to enter the market in 2020 with potential blockbuster status (see Table I at end of article). Below are snapshot views of these and the other drugs entering the market in 2020 with blockbuster potential.

Eleven potential blockbusters

Novo Nordisk’s Rybelsus (semaglutide) oral, once daily. Novo Nordisk’s Rybelsus (semaglutide) an oral, once-daily medicine for treating Type II diabetes, is a strong contender for blockbuster status with 2024 projected sales of $3.215 billion, according to the Clarivate Analytics’ Cortellis analysis. Rybelsus (semaglutide) oral tablets were approved by the US Food and Drug Administration (FDA) in September 2019 to improve control of blood sugar in adult patients with Type 2 diabetes, along with diet and exercise. Rybelsus was the first glucagon-like peptide (GLP-1) receptor protein treatment approved for use in the US that does not need to be injected, according to the FDA. Novo Nordisk has an injectable version of semaglutide in Ozempic, which was first approved by the FDA in 2017 and which posted 2019 sales of DKK 11.237 billion ($1.6 billion).

The oral administration of Rybelsus is one of the competitive advantages it will have over injectable GLP-1 agonists, according to an analysis by BioWorld, which provided further examination of the disease landscape of the blockbuster list. Cardiovascular (CV) safety data were also added to the drug’s label in January 2020. Additional filings for adults with Type 2 diabetes have also been submitted in the European Union and Canada. Rybelsus combines the convenience of a once-daily pill with the glucose-lowering activity and the CV benefits of injectable GLP-1 agonists, which is seen as the main reason it could have a major impact on the diabetes market, according to the BioWorld analysis.

AstraZeneca’s and Daiichi Sankyo’s Enhertu (fam-trastuzumab deruxtecan-nxki). Daiichi Sankyo’s and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) for treating unresectable or metastatic HER2-positive breast cancer is one of three oncology drugs set to launch in 2020 with blockbuster potential and one of two antibody drug conjugates (ADCs) in the list. It has 2024 projected sales of $2.020 billion, according to the Clarivate Analytics’ Cortellis analysis. The drug was approved by the FDA in December 2019 and was launched in the US in January 2020 for treating adults with unresectable or HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. HER2-positive breast cancer is a type of breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. Approximately one of every five breast cancers have a gene mutation in the cancer cells that makes an excess of the HER2 protein, according to information from the FDA. Enhertu is a HER2-directed antibody and topoisomerase inhibitor conjugate, meaning that the drug targets the changes in HER2 that help the cancer grow, divide and spread, and is linked to a topoisomerise inhibitor, which is a chemical compound that is toxic to cancer cells, according to information from the FDA.

Enhertu has entered a market dominated by Roche’s Herceptin (trastuzumab) and other HER2-targeted therapies, such as Roche’s Perjeta (pertuzumab) and Novartis’ Tykerb (lapatinib), which was developed by GlaxoSmithKline and acquired by Novartis in 2015, according to the Clarivate Analytics’ Cortellis analysis. Roche’s Kadcyla (trastuzumab emtansine), the only other ADC in the HER-2-positive breast-cancer market, is a direct competitor and differentiations of it versus Enhertu will be key, according to the BioWorld analysis. Enhertu also is potentially being targeted in development for other cancers, including gastric, colorectal and non-small-cell cancer.

In 2019, AstraZeneca and Daiichi entered into a $6.8-billion deal for the development and commercialization of Enhertu. The companies jointly developed and are commercializing trastuzumab deruxtecan worldwide, except in Japan, where Daiichi Sankyo maintain exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply. Under the deal, AstraZeneca was responsible for an upfront payment of $1.35 billion to Daiichi Sankyo and is responsible for contingent payments of up to $5.55 billion, which include $3.8 billion for potential successful achievement of future regulatory and other milestones as well as $1.75 billion for sales-related milestones.

Immunomedics’ sacituzumab govitecan. Immunomedics’ sacituzumab govitecan for treating metastatic triple-negative breast cancer is the second ADC on the list of potential blockbusters with projected 2024 sales of $1.270 billion, according to the Clarivate Analytics’ Cortellis analysis. In December 2019, the FDA accepted the resubmission of Immunmedics’ biologics license application (BLA) for sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease. The Prescription Drug User Fee Act (PDUFA) target action date of the resubmitted BLA is June 2, 2020, according to company information. Sacituzumab govitecan was granted both fast-track designation and breakthrough therapy designation by the FDA.

Bristol-Myers Squibb’s liso-cel (lisocabtagene maraleucel). Bristol-Myers-Squibb’s (BMS) liso-cel (lisocabtagene maraleucel), a CAR T therapy for treating large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) in which specifically designed T cells seek and destroy CD19-expressing cancer cells, is the third oncology drug on the list with potential blockbuster status with projected 2024 sales of $1.089 billion, according to the Clarivate Analytics’ Cortellis analysis. BMS acquired the medicine in its $74-billion acquisition of Celgene, which was completed in November 2019.

In December 2019, BMS submitted a BLA for treating adult patients with relapsed or refractory large B-cell lymphoma after at least two prior therapies. The BioWorld analysis notes that the medicine would potentially compete against two other CAR T therapies for treating DLBCL: Gilead Sciences’ Yescarta (axicabtagene ciloleucel), which was the first DLBCL CAR T-cell approved by the FDA for treating relapsed or refractory DLBCL in October 2017, and Novartis’ Kymriah (tisagenlecleucel), which was approved by the FDA for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in May 2018.

Liso-cel was granted breakthrough therapy and regenerative medicine advanced therapy designations by the FDA for relapsed/refractory aggressive large B-cell non-Hodgkin lymphoma, including DLBCL, not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma or Grade 3B follicular lymphoma, and Priority Medicines (PRIME) scheme by the European Medicines Agency (EMA) for relapsed/refractory DLBCL, according to information from BMS.

Bristol-Myers Squibb’s ozanimod. BMS’ ozanimod for treating relapsing forms of MS is the second potential blockbuster for the company on the list with projected 2024 sales of $1.621 billion, according to the Clarivate Analytics’ Cortellis analysis, and was acquired by BMS in its acquisition of Celgene in 2019.

The drug, which is under regulatory review by both the FDA and the EMA, may be the next approved oral MS therapeutic, according to the BioWorld analysis. The PFUDA review date by the FDA is March 25, 2020, and the EMA is expected to review the drug in the first half of 2020.

Ozanimod is an oral agonist of the sphingosine 1-phosphatase (S1P) 1 and 5 receptors. It will compete against other oral drugs to treat relapsing forms of MS with similar mechanisms of action: Novartis’ Gilenya (fingolimod), which was approved in 2010, Novartis’ Mayzent (siponimod), which was approved in 2019, and Merck KGaA’s Mavenclad (cladribine), which was also approved in 2019. On a competitive basis, both Mayzent and Gilenya require additional testing before a patient can take either drug, which may offer further potential for ozanimod, according to the BioWorld analysis. Other competition from other oral MS drugs with similar mechanisms of action, include: Biogen’s Tecfidera (dimethyl fumarate), Sanofi’s Aubagio (teriflunomide) and Johnson & Johnson’s investigational drug ponesimod. Other oral competitors with different mechanisms are Biogen’s and Alkermes’ Vumerity (diroximel fumarate) approved by the FDA in October 2019.

Novartis’ ofatumumab (subcutaneous). Novartis’ ofatumumab (subcutaneous) is another MS drug expected to be launched in 2020 with blockbuster potential with projected 2024 sales of $1.261 billion, according to the Clarivate Analytics’ Cortellis analysis. It contains the same active ingredient, ofatumumab, as Novartis’ anticancer drug, Arzerra. It is an anti-CD20 monoclonal antibody that binds to CD20 to eradicate the B cells that would otherwise attack the myelin, the sheath that forms around nerves.

One of the main competitors to ofatumumab (subcutaneous) is Roche’s Ocrevus (ocrelizumab), but ofatumumab (subcutaneous) seeks to compete on mode of delivery. Ocrevus requires a visit to an infusion center, whereas ofatumumab is a self-injection at home, according to the BioWorld analysis.

Novartis’ inclisiran. Novartis’ inclisiran for treating familial hypercholesterolaemia, an inherited disorder that results in high levels of low-density lipoprotein cholesterol (LDL-C), is the second potential blockbuster from Novartis on the list of drugs with expected 2020 launch. Novartis acquired the drug in its $9.7-billion acquisition of The Medicines Company, in January 2020. Projected 2024 sales are $1.161 billion, according to the Clarivate Analytics’ Cortellis analysis.

In December 2019, The Medicines Company submitted a new drug application for inclisiran to the FDA for use in secondary prevention patients with atherosclerotic cardiovascular disease and familial hypercholesterolaemia. Inclisiran is a small interfering RNA (siRNA) drug and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. It would compete against PCSK9-targeting antibodies, such as Sanofi’s and Regeneron Pharmaceuticals’ Praluent (alirocumab) and Amgen’s Repatha (evolocumab) as well as other cholesterol-lowering drugs such as statins.

Gilead Sciences’ filgotinib. Gilead Sciences’ filgotinib for treating rheumatoid arthritis, one of several targeted indications, has projected 2024 sales of $1.422 billion, according to the Clarivate Analytics’ Cortellis analysis. The drug is an oral inhibitor of Janus kinase (JAK) 1; overactivation/dysregulation of JAK1 can lead to autoimmune responses, according to the BioWorld Analysis. Filgotinib is currently up for approval as a treatment for rheumatoid arthritis, with marketing applications for the initial indication filed in the EU in August 2019, in Japan in October 2019, and in the US in December 2019. Gilead Sciences is using a priority review voucher with the FDA to shorten the review time by four months. Gilead is partnered with Galapagos and Eisai, which will market filgotinib in various regions.

The drug will compete against other drugs to treat rheumatoid arthritis with different mechanisms of action, such as AbbVie’s Humira (adalimumab), BMS’ Orencia (abatacept), Sobi’s Kineret (anakinra), Sanofi’s and Regeneron’s Kevzara (sarilumab), Roche’s Actemra (tocilizumab), and Roche’s/Biogen’s Rituxan (rituximab) as well as multiple other JAK inhibitors, including Pfizer’s Xeljanz (tofacitinib), Eli Lilly and Company’s Olumiant (baricitinib) and AbbVie’s Rinvoq (upadacitinib).

Gilead and Galapagos are also testing filgotinib as a treatment for ulcerative colitis, Crohn’s disease, psoriatic arthritis and ankylosing spondylitis, potentially resulting in five approvals over the next four years, according to the BioWorld analysis.

Akebia Therapeutics’, Mitsubishi Tanabe Pharma’s, and Otsuka Pharmaceutical’s vadadustat. Akebia Therapeutics’, Mitsubishi Tanabe Pharma’s, and Otsuka Pharmaceutical’s vadadustat for treating anemia related to chronic kidney disease is another potential blockbuster to be launched in 2020 with 2024 projected sales of nearly $1.6 billion, according to the Clarivate Analytics’ Cortellis’ analysis.

Akebia is developing the drug in partnership with Otsuka Pharmaceutical and Mitsubishi Tanabe Pharma. In 2016, Akebia entered into a collaboration and license agreement with Otsuka for the development and commercialization of vadadustat in the US and in 2017, Akebia expanded its relationship with Otsuka to develop and commercialize vadadustat in Europe, China, Russia, Canada, Australia, the Middle East, and certain other territories. In 2015, Akebia entered into a collaboration agreement with Mitsubishi Tanabe Pharma with exclusive development and commercialization rights to vadadustat in Japan and certain other Asian countries. Mitsubishi Tanabe Pharma submitted a Japanese new drug application for vadadustat to Japan’s Ministry of Health, Labor and Welfare in July 2019, representing the first regulatory submission for vadadustat. If approved, the company expects commercial launch during mid-2020, and filings in the US and the European Union are planned.

BioMarin Pharmaceutical’s Valrox (valoctocogene roxaparvovec). BioMarin Pharmaceutical’s Valrox (valoctocogene roxaparvovec) is an investigational adeno-associated virus-based gene therapy for treating adults with hemophilia A. The therapy is designed to deliver functional copies of the FVIII gene into patients’ cells, enabling them to make the previously missing or defective FVIII protein, according to the BioWorld analysis. If approved, Valrox would be the first potentially curative (one and done) approach to hemophilia A, eliminating the need for blood transfusions and FVIII replacement therapy after a single infusion. Clarivate Analytics’ Cortellis projects 2024 sales of $1.3 billion.

Biohaven Pharmaceuticals’ rimegepant. Biohaven Pharmaceuticals’ rimegepant for treating migraines is another drug with expected launch in 2020 with blockbuster potential. Clarivate Analytics’ Cortellis projects 2024 sales of $1.03 billion. If approved, the drug would be a new oral option for patients with acute, or episodic, attacks of migraines and would be the second oral small-molecule calcitonin gene-related peptide (CGRP) antagonist approved; the other was Allergan’s Ubrelvy (ubrogepant), which was approved by the FDA in December 2019. These two oral medicines follow three injectables in the CGRP class that entered the market in 2018, according to the BioWorld analysis.