Blockbuster Watch for 2019: What Drugs Will Make the Mark?

Clarivate Analytics’ Cortellis Drugs to Watch 2019 Report identifies seven drugs that are set to enter the market in 2019 and achieve blockbuster status by 2023. Which drugs are projected to make the mark?

Examing the potential blockbusters

In its Cortellis Drugs to Watch 2019 ReportClarivate Analytics identifies seven new drugs forecast to achieve annual sales of $1 billion or more (i.e., blockbuster status) by 2023. The analysis is based on data from the Cortellis database, which includes information gathered from diverse sources including drug pipelines, patents, clinical trials, chemistry, deals and company announcements. Immune-related and genetic disorder products dominate the list, with a strong showing by orphan drugs and breakthrough-therapy treatments.

Six out of the seven projected blockbusters target diseases characterized by genetic disorder and/or excessive immune response, including autoimmunity. The projected blockbusters also reflect the move to more targeted clinical therapies by focusing on rare diseases and/or unmet needs and conditions not addressed by current treatments due to safety, efficacy, convenience, or other issues. These are reflected in the various regulatory designations of the indications of the drugs: nine US, four European Union (EU) and one Japanese orphan drug designations; four US breakthrough therapy designations; two EU PRIority MEdicines (PRIME) designations; one US regenerative medicine advanced therapy designation; and one Japanese Sakigake designation.

Among the large pharma companies, AbbVie (with one drug singularly and for a second with Boehringer Ingelheim), Novartis, and AstraZeneca/Astellas Pharma (in co-development and commercialization with Fibrogen) have drugs that made the Cortellis Drugs to Watch list with smaller companies, Alexion Pharmaceuticals, Aimmune Therapeutics, and bluebird bio, rounding out the list. The list of seven projected blockbusters include two small molecules, three biologics, and two gene therapies. Table I (see end of article) identifies the drugs that are projected to enter the market in 2019 and reach blockbuster status by 2023.

Seven potential blockbusters

1. AbbVie’s upadacitinib. Abbvie’s upadacitinib is a small-molecule JAK1 selective inhibitor being investigated to treat rheumatoid arthritis, Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis and axial spondyloarthritis and is projected by Cortellis to achieve $2.2 billion in sales by 2023.

Upadacitinib was filed for approval in the US and EU in December 2018 and accepted for priority review in February 2019. Cortellis forecasts US approval in August 2019 and EU approval in October 2019.

Upadacitinib for treating rheumatoid arthritis will be a late entrant to the market that already includes biologic-based drugs that inhibit the pro-inflammatory mediator tumornecrosis factor (TNF), such as AbbVie’s Humira (adalimumab), Amgen’s Enbrel (etanercept) (also co-marketed by Pfizer and Takeda), Johnson & Johnson’s Simponi (golimumab) and Remicade (infliximab) (also co-marketed by Mitsubishi Tanabe; and a biosimlar by Merck & Co.), and UCB’s/Astella’s Cimzia (certolizumab pegol). Biosimilar versions of Humira entered the EU market in 2018 and are set to launch in the US in 2023, creating additional pressures in this already complex market, according to the Cortellis analysis.

The drug will also face competition from non-TNF biologicals, such as Roche’s/Chugai’s Actemra (tocilizumab); Bristol-Myers Squibb’s and Ono Therapeutics’ Orencia (abatacept), and Roche’s/Biogen’s Rituxan (rituximab). Upadacitinib will also face direct competition from other JAK inhibitors, namely Pfizer’s Xeljanz (tofacitinib), which had 2018 sales of $1.77 billion with forecast sales rising to $3.31 billion in 2023, according to the Cortellis analysis. Eli Lilly’s and Incyte’s Olumiant (baricitinib), which is selective for JAK1/JAK2, entered the EU and Japanese markets in 2017 and the US market in 2018; sales of $977 million are forecasted for 2023.

2. Novartis’ Zolgensma (onasemnogene abeparvovec). Novartis gained Zolgensma, a gene-replacement therapy for treating spinal muscular atrophy, a neuromuscular disease, from its $8.9-billion acquisition of AveXis, a Bannockburn, Illinois-headquartered clinical-stage gene-therapy company, in 2018. Cortellis projects annual revenues of $2.09 billion by 2023 and 2019 revenues of $449 million.

Zolgensma corrects the genetic defect underlying spinal muscular atrophy, which is caused by SMN1 gene mutations, which block production of the survival motor neuron (SMN) protein that is essential for transmitting motor signals from the brain to the muscles. Without the SMN protein, motor neurons die. As a result, those affected have muscle weakness and wasting that creates difficulty moving, breathing and swallowing. AveXis’/Novartis’s Zolgensma is an injectable gene therapy that uses a viral vector to introduce DNA for a functional SMN protein into a patient’s cells. This enables the cells to make the missing SMN protein.

Zolgensma will face immediate competition from Biogen’s Spinraza (nusinersen), an antisense oligonucleotide injectable, which has been available in the US since 2016 and the EU since 2017, according to the Cortellis analysis. Spinraza sales were $1.72 billion in 2018, according to information from Biogen, and are forecast to climb to $2.26 billion in 2023, according to the Cortellis analysis. While Zolgensma has currently only been filed for approval in SMA type I, Spinraza is approved for all SMA types. However, Zolgensma is given as a more convenient single onetime dose via an intravenous injection while Spinraza must be administered every four months into the cerebrospinal fluid via lumbar puncture (intrathecally).

AveXis filed Zolgensma for approval in the US, EU, and Japan in the third quarter of 2018 for the treatment of SMA Type I. The companies expect to launch the drug in the US and Japan in the first half of 2019, and in the EU in the second half of 2019.

Other therapies in development that could compete with Zolgensma are Roche’s risdiplam and Novartis’s branaplam and Cytokinetics’s and Astellas’s reldesemtiv.

3. AstraZeneca’s/FibroGen’s/Astellas’s roxadustat. With projected 2023 annual sales of $1.97 billion, roxadustat is a small-molecule hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor for treating patients with anemia caused by chronic kidney disease (CKD) and who are on dialysis. FibroGen, a San Francisco-based biopharmaceutical company, is the originator of the drug and is collaborating with AstraZeneca on the development and commercialization of roxadustat in the US, China, and other global markets and with Astellas Pharma in Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa.

Roxadustat was approved in December 2018 in China for the treatment of CKD-related anemia in patients dependent on kidney dialysis. Launch is expected in the second half of 2019, and approval for use in patients not on dialysis is expected in mid-2019. The drug is under regulatory review in Japan, where a filing for anemia in CKD patients on dialysis was submitted in October 2018. A US filing is expected in the third quarter of 2019.

The main competing therapies for roxadustat are erythropoiesis-stimulating agents, which are medications which stimulates the bone marrow to make red blood cells, which although well established, present certain drawbacks, according to the Cortellis analysis. Roxadustat potentially faces competition from other HIF-PH inhibitors currently in clinical development, such as GlaxoSmithKline’s daprodustat and vadadustat from Akebia Therapeutics, Mitsubishi Tanabe, and Otsuka.

4. Alexion Pharmaceuticals’ Ultomiris (ravulizumab). Ultomiris (ravulizumab), with projected annual sales from Cortellis of $1.93 billion, is a rare-disease drug by Alexion Pharmaceuticals, a New Haven, Connecticut-based biopharmaceutical company, for treating adults with paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare blood disorder characterized by complement-mediated destruction of the red blood cells (hemolysis). The drug, a monoclonal antibody, was approved by the FDA in December 2018 and launched in January 2019. It received a positive opinion for approval by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in April 2019.

Ultomiris is a next-generation product of another Alexion drug, Soliris (eculizumab), also a treatment for PNH as well as two other rare diseases (atypical hemolytic uremic syndrome, a blood disorder, and generalized myasthenia gravis, a chronic autoimmune neuromuscular disease). Soliris, which was first approved for PNH in 2007, posted 2018 sales of $3.56 billion. Ultomiris is designed to be longer acting than Soliris, and is thus dosed only every eight weeks, instead of every two for Soliris.

There is also potential competition in the PNH development pipeline from other complement inhibitors, such as Akari Therapeutics’s Coversin (nomacopan), Apellis’s APL-2, Achillion’s danicopan, and Ra Pharmaceutical’s zilucoplan.

5. Boehringer Ingelheim’s/AbbVie’s Skyrizi (risankizumab). Cortellis projects 2023 annual sales of $1.74 billion for Skyrizi (risankizumab), a biologic-based drug for treating psoriasis and part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

The drug, an interleukin-23 (IL-23) inhibitor, was approved by the FDA in April 2019 for treating moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It also recently received approval from the Japanese Ministry of Health, Labour and Welfare for treating plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis, as well as from Health Canada for treating moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The drug also received a positive opinion from the EMA’s CHMP, which recommended marketing authorization for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy. A regulatory decision in Europe is expected in the first half of this year, according to information from AbbVie.

Skyrizi will compete with different treatment modalities, such as topicals, light treatments, and systemic medicines, including entrenched biological agents and biosimilar biologicals, according to the Cortellis analysis. Competing non-biological systemic agents include methotrexate and Celgene’s Otezla (apremilast), an oral anti-inflammatory agent. Competing biological systemic agents include the TNF inhibitors, AbbVie’s Humira (adalimumab) and Amgen’s Enbrel (etanercept), which also have biosimilar versions. Other competitors are: Johnson & Johnson’s Stelara, an IL-12/IL-23 inhibitor; the IL-23 inhibitors of Sun Pharmaceutical’s/Almirall’s Ilumya (tildrakizumab) and Johnson & Johnson’s Tremfya (guselkumab); and Novartis’ Cosentyx (secukinumab), an IL-17 inhibitor.

6. Aimmune Therapeutics’ AR-101. Cortellis projects 2023 annual sales of $1.17 billion for AR-101, a treatment to reduce the risk of anaphylaxis following accidental exposure to peanuts from Aimmune Therapeutics, a Brisbane, California-based biopharmaceutical company.

In March 2019, the FDA accepted for review the company’s biologics license application (BLA) for AR101. Aimmune Therapeutics reported that the FDA informed the company that the BLA will be reviewed under a 12-month target review period, as measured from the January 2019 start date, and as such, review of the BLA may take until late January 2020. Aimmune says it is currently engaged in discussions with the FDA regarding the review timeline for the AR101 BLA, with the FDA expecting to convene an advisory committee meeting to discuss the application. The FDA granted AR101 breakthrough therapy designation in June 2015 for peanut-allergic children and adolescents ages 4-17, which was preceded by the granting of fast-track designation in September 2014. Aimmune expects to file for marketing approval of AR101 in Europe in mid-2019.

AR-101 has the potential to be the first oral immunotherapy for inducing food-allergen tolerance, according to the Cortellis analysis. It may, however, face competition from other peanut desensitization therapies that are currently in development. For example, DBV Technologies, a Bagneux, France-based biopharmaceutical company, filed its Viaskin Peanut transdermal therapy for US approval for children aged 4 to 11 years in October 2018, but withdrew the filing in December 2018 after discussions with the FDA regarding the insufficiency of the manufacturing procedure. The company reported that it plans to resubmit its filing in October 2019. Also in development are ProTA Therapeutics’s probiotic and peanut oral immunotherapy and Camallergy’s oral peanut immunotherapy (CA-002), both of which are expected to enter Phase III trials in the near term.

7. bluebird bio’s LentiGlobin (betibeglogene darolentivec). bluebird bio’s LentiGlobin (betibeglogene darolentivec) is the second gene therapy to make the list of drugs expected to enter the market in 2019 and to reach blockbuster status by 2023 with projected sales of $1.12 billion. LentiGlobin is being developed for the treatment of transfusion-dependent β-thalassemia (TDT). TDT is an inherited blood disorder caused by a mutation in the β-globin gene, which causes ineffective red blood cell production leading to severe anemia. Its only immediate competition will be donor stem-cell transplant. bluebird bio’s LentiGlobin therapy provides an alternative. Instead of using donor cells, the patient’s own cells are harvested, genetically modified to produce functional beta-globin, and then re-introduced back into the patient, thus correcting the disease.

European approval of LentiGlobin in patients with TDT and non-β0/β0 genotypes is expected by the end of 2019, according to a February 2019 update from the company. Filing for US approval of LentiGlobin in patients with TDT and non-β0/β0 genotypes is by the end of 2019.

Further information on the Cortellis Drugs to Watch 2019 Report, including how to download, may be found here.

Table I: Seven New Drugs Forecast to Enter the Market in 2019 and Achieve Blockbuster Sales of Over $1 Billion by 2023 (data as of March 5, 2019).
Drug (Proprietary Name and Active ingredient Disease 2019 Projected Sales 2023 Projected Sales Company (HQ)
Upadacitinib *§†| (ABT-494) Rheumatoid arthritis $53 M $2.20 B AbbVie (US)
Zolgensma Δ†|‡§ (onasemnogene abeparvovec; AVXS-101) Spinal muscular atrophy $449 M $2.09 B AveXis (US) (a Novartis subsidiary)
Roxadustat (FG-4592; AZD-9941; ASP-1517) Anemia in chronic kidney disease patients on dialysis $30 M $1.97 B AstraZeneca(UK); FibroGen (US);Astellas (JPN)
Ultomiris Δ§|(ravulizumab; ALXN-1210) Paroxysmal nocturnal hemoglobinuria $170 M $1.93 B Alexion (US)
Skyrizi *| (risankizumab; BI-655066; ABBV-066) Psoriasis $132 M $1.74 B Boehringer Ingelheim (Germany); AbbVie (US))
AR-101 *†|‡ ‡‡ Peanut allergy $35 M $1.17 B Aimmune Therapeutics (US)
LentiGlobin Δ†|‡ (betibeglogene darolentivec) Beta-thalassemia in transfusion-dependent patients $11 M $1.12 B bluebird bio (US)

Data were obtained from the Cortellis Competitive Intelligence database, accessed March 5, 2019. Forecasts are in US$ million( M) and billion (B).

*=immune-related disease. Δ=genetic disorder. †=Breakthrough Therapy designation. ‡=Fast Track designation. |=Orphan Drug designation. §=Priority Review. ‡‡=first-in-class.

Source: Clarivate Analytics’ Cortellis Drugs to Watch 2019 Report.

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