The most noteworthy drugs of 2019
Corey Vivian's Cortellis team recently released a report predicting that there are 7 most noteworthy drugs in 2019 (see table), and their sales within 5 years after they are on the market are expected to reach the "blockbuster" level (reaching or exceeding $1 billion).
These seven drugs have three things in common: the first is to face diversified competition; the second is that the disease field is highly concentrated, and the treatment areas of the seven drugs are almost all concentrated in the "genetic disease" and "excessive immune response (including autoimmunity)" The characteristic disease area; the third is that homogenized drugs are in sharp contrast to niche drugs. The development of niche drugs attracts more investment than the highly competitive fast-follow drug development model. The breakthrough points of these drugs mainly focus on "rare disease drugs", "unmet clinical needs", "defects in safety, effectiveness, and compliance. A large proportion of the seven drugs of concern in 2019 are niche drugs, and most of these drugs have received priority reviews, breakthrough therapies or fast-track reviews. These 7 drugs specifically include:
1. New drugs for rheumatoid arthritis: Upadacitinib
Rheumatoid arthritis is a chronic, progressive, aggressive autoimmune disease, its pathogenesis is not clear, there is no clinical cure. The main purpose of drug treatment is to reduce symptoms and delay the onset of the disease. In terms of incidence, rheumatoid arthritis affects 0.3 to 1% of the global population.
Upadacitinib is an oral JAK1 inhibitor developed by AbbVie. The disorder of the regulatory function of JAK family molecules is related to the production of proinflammatory mediators in the pathogenesis of rheumatoid arthritis. Therefore, inhibition of JAK protein can effectively control rheumatoid arthritis.
In December 2018, AbbVie submitted Upadacitinib new drug applications to the United States and the European Union. The Cortellis team predicts that the drug has a 95% approval success rate in both the United States and the European Union. In terms of time, the drug will be available in the United States in September 2019 and in the European Union in October 2019. From the market forecast, sales of the drug will exceed $2.2 billion by 2023.
In addition to rheumatoid arthritis, phase III clinical trials Upadacitinib the treatment of ulcerative colitis, psoriatic arthritis, Crohn's disease and atopic dermatitis are under way; clinical trials for the treatment of ankylosing spondylitis have also been carried out. Phase II; clinical trial plans for the treatment of giant cell arteritis have also been launched.
If the Upadacitinib is successfully approved, it is expected to be listed in 2019. However, after the drug is listed, it will face fierce competition from similar drugs (especially biological drugs), and most of these biological drugs are recommend drugs that have been used clinically for many years.
Biopharmaceuticals are the market leader in this field, and the mechanism of action of most products is TNF inhibitors, such as Humira (Humira), Enbrel (Enbrel), Simponi (Hempney), Remicade (Bike) and Cimzia. The American College of Rheumatology Guidelines for the Treatment of Rheumatoid Arthritis recommend these drugs as second-line antirheumatic agents. In addition to branded biologics, the availability of biosimilants has further increased the level of competition in the field. For example, Humira (with 2017 sales of $18.77 billion) has attracted many generic drug companies. Its biosimilars entered the EU market in 2018 and will be available in the United States in 2023.
In addition to TNF inhibitors being recommend as second-line drugs for anti-rheumatic diseases, "non-TNF inhibitors" are usually recommend as second-line drugs in clinical practice before the use of the latest drugs. Such as Actemra (yamalopol), Orencia (abatacept), Rituxan (raloxine), etc., which are clinically positioned as alternative products of TNF biological drugs or second-line drugs after failure of TNF inhibitor therapy.
In addition to biologics, Upadacitinib will also face direct competition from other JAK inhibitors. The field's First-in-Class drug Xeljanz (Shang Jie) is a broad-spectrum JAK inhibitor. The American College of Rheumatology recommends it as a second-line drug for failure of biologic therapy. In 2017, Xeljanz sales were $1.35 billion and are expected to grow to $3.19 billion in 2023.
Lilly's Olumiant, a selective inhibitor of JAK1/JAK2, entered the EU and Japanese markets in 2017 and the US market in 2018. In 2017, Olumiant had sales of $45 million, and in 2023 sales are expected to top $1.06 billion (about half of Upadacitinib). Olumiant also faces many challenges, such as the black box warning on its label is more extensive than Xeljanz.
2. New drugs for spinal muscular atrophy: Zolgensma
Zolgensma was developed by AveXis in conjunction with Novartis as a gene therapy drug delivered by injection. In the third quarter of 2018, AveXis submitted a Zolgensma marketing application to the United States, the European Union and Japan for the treatment of type I spinal muscular atrophy. According to the Cortellis team, the drug has an approval success rate of 95% in the United States, the European Union and Japan. It is expected that Zolgensma sales will reach $0.76 billion this year, increase to $1.27 billion in 2020, and exceed $2.2 billion in 2023.
In 2016, the First-in-Class drug in this field was Spinraza listed in the United States and in 2017 in the European Union. The drug was once qualified as an orphan drug and breakthrough therapy. If the Zolgensma is successfully approved, it will also face fierce market competition.
The Spinraza, jointly developed by Ionis Pharmaceuticals and Biogen, was approved in the United States in December 2016 and became the first drug for SMA treatment in the United States. In June 2017, Spinraza was approved in the European Union. In 2017, the drug achieved global sales revenue of $0.883 billion, and the Cortellis team predicts that the drug's sales will exceed $2.27 billion in 2023.
In terms of the scope of approval, Zolgensma currently approved only for type I SMA does not appear to be an advantage over Spinraza approved for all types of SMA. However, from a compliance point of view, administration Zolgensma be done at once by intravenous injection, whereas Spinraza have to be Zolgensma by lumbar puncture (intrathecal) injection of cerebrospinal fluid every 4 months.
Of course, in order to make up for the lack of Zolgensma in the scope of indications approved, AveXis is actively carrying out relevant clinical trials, with a view to expanding the use of Zolgensma to other types of SMA. At the same time, in terms of compliance, AveXis also tried intrathecal administration with poor compliance, but the frequency of administration is still one-time administration, which is more advantageous than regular continuous administration. The Cortellis team predicts that in the second half of 2019, AveXis will submit Zolgensma marketing applications for the treatment of type II and III SMA.
In addition to Spinraza, there are not many drugs in the research and development stage that can compete positively with Zolgensma in the future. Among them, Roche's Risdiwam and Novartis's Branaplam are more promising. In addition, the Reldesemtiv jointly developed by Cytokinetics and Astellas is also an important competitor in this field.
3. New drugs for chronic kidney disease anemia: Roxadustat
In patients with chronic kidney disease, anemia is a common complication and gradually worsens with the progression of kidney disease. Most patients with chronic kidney disease progressing to renal failure are accompanied by anemia. In terms of global incidence, chronic kidney disease affects 0.2 billion people.
Roxadustat (roxalustat) is a therapeutic drug for chronic kidney disease anemia jointly developed by AstraZeneca, FibroGen and Astella. It is the first-in-class of hypoxia-inducible factor-proline hydroxylase (HIF-PH) inhibitor. From the mechanism of action, proline hydroxylase is an enzyme that breaks down hypoxia-inducible factor, which is involved in the production of erythropoietin (EPO) and iron. Roxadustat promotes the production of red blood cells by inhibiting proline hydroxylase, protecting hypoxia-inducible factor, stimulating the production of EPO and iron. The Cortellis team predicts sales of the drug will reach $1.97 billion in 2023.
In December 2018, the drug was approved in China for the treatment of "kidney dialysis-dependent chronic kidney disease anemia" and is expected to be available in the second half of 2019. In addition, the application for the drug for "non-kidney dialysis dependent chronic kidney disease anemia" has also been submitted to the Chinese drug regulatory authorities.
In terms of market competition, GSK (GlaxoSmithKline), Akebia, Mitsubishi Tanbian, Otsuka and other companies are all competitors in this field, especially GSK's Daprodustat and Akebia's Vadustat.
In 2016, GSK initiated a Phase III clinical trial for a different type of chronic kidney disease anemia. After releasing positive data in 2018, GSK plans to file a listing application in Japan in 2019. The Cortellis team predicts that the drug will be approved in Japan in 2020, with an approval success rate of 90%. In the United States and Europe, Daprodustat is currently in Phase 3 clinical trials, with completion expected in 2020. The Cortellis team predicts that the Daprodustat will be approved by the United States and the European Union in 2021, with an approval success rate of 86%. On the market side, Daprodustat sales are expected to exceed $0.217 billion by 2023.
Akebia's Vadadustat entered the clinical trial stage of "non-renal dialysis dependent chronic kidney disease anemia" and "renal dialysis dependent chronic kidney disease anemia" in the United States and the European Union in 2015 and 2016 respectively. Akebia is expected to submit applications for listing in these regions in 2019. The Cortellis team predicts that the drug will be approved in the United States and the European Union in 2021, with an approval success rate of 85%. In Japan, Vadadustat Phase III clinical trials for "Non-dialysis-dependent chronic kidney disease anemia" and "Renal dialysis-dependent chronic kidney disease anemia" were initiated in 2017 and 2018, respectively. The Cortellis team expects the Vadadustat to be approved in Japan in 2021, with an 86 percent approval success rate. On the market side, Vadadustat sales are expected to reach $0.85 billion in 2023.
4. New drug for paroxysmal nocturnal hemoglobinuria: Ultomiris
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired blood disease that affects 1 to 5 people per million people. Due to genetic defects, patients' red blood cells are easily destroyed by a substance called complement, leading to the formation of blood clots, which in turn can lead to death or organ damage.
Alexion Ultomiris is the next generation of the "blockbuster" product Soliris in the PNH field. Compared with the Soliris once every two weeks, Ultomiris once every 8 weeks, compliance has been greatly improved.
In December 2018, the US FDA approved Ultomiris for the treatment of adult patients with PNH. From the submission of the listing application to the approval of the Ultomiris, it took only six months, two months ahead of the FDA's target time to complete the priority review. In January 2019, the drug was already available in the United States.
In 2007, Soliris was approved by the FDA for the treatment of PNH, the first drug to be used in the treatment of PNH. Although PNH is a very rare disease, Soliris took advantage of the pricing of "orphan drugs" to achieve its "blockbuster" status. In 2017, Soliris had sales of $3.14 billion. The Cortellis team predicts that sales of the drug will exceed $3.78 billion in 2023. Soliris next-generation product Ultomiris, the market share will be more advantageous. The Cortellis team predicts sales of $1.93 billion in the Ultomiris2023 year.
The competition for Ultomiris comes mainly from other complement inhibitors in the late clinical stage, such as Akari's Coversin, Apellis's APL-2, Achilion's Danicopan, and Ra's pharmaceutical Zilucoplan.
In March 2017, Coversin entered the phase III clinical trial of PNH; in June 2018, APL-2 entered the phase III clinical trial of PNH. The Cortellis team predicts that the above two drugs will be approved in 2021, with approval success rates of 86% and 81%, respectively.
Danicopan and Zilucoplan are currently in Phase 2 clinical trials. According to the Cortellis team's prediction, the Danicopan will be approved in 2022 in both the United States and the European Union, with an approval success rate of 54%. In terms of the market, the drug is expected to have sales of $0.609 billion in 2023. Zilucoplan is also approved in the United States in 2022, with an approval success rate of 56%, and in the European Union in 2023, with an approval success rate of 62%. It is expected that Zilucoplan sales in 2023 will exceed $0.154 billion.
5. New Psoriasis Drug: Risankizumab
Psoriasis is a chronic inflammatory skin disease, which is caused by T lymphocytes and neutrophils in the immune system attacking healthy skin cells. The deep-seated mechanism of action is still unclear. The incidence of the disease varies widely worldwide, ranging from 1.5 to 5% in most developed countries and regions.
Risankizumab, a monoclonal antibody developed by Boehringer Ingelheim and AbbVie, works by inhibiting pro-inflammatory cytokine IL-23. The holders of Risankizumab submitted marketing applications for the drug for moderate to severe plaque psoriasis to the United States, the European Union and Japan in April and May 2018, respectively, and also submitted marketing applications for the drug for plaque psoriasis, psoriatic arthritis, pustular psoriasis and erythrodermic psoriasis in Japan. The Cortellis team predicts that the success rate of the drug's approval in the above countries and regions is 95%, and sales in Risankizumab are expected to exceed $1.74 billion in 2023.
Clinically, there are a variety of treatments for psoriasis, such as local treatment, phototherapy, systemic drug therapy and so on. Among over-the-counter drugs, salicylic acid, coal tar, etc. are common. These drugs have a long history of psoriasis treatment; among prescription drugs, corticosteroids, retinoic acid and vitamin D analogs are commonly used for external use. In addition, phototherapy has become an important means for the treatment of psoriasis because of its good safety, effectiveness, cost-effectiveness, low systemic toxicity and immunosuppression. In terms of systemic drug treatment, methotrexate has become a common drug for moderate to severe psoriasis in the world because of its low price. However, aprester, which has only entered the market in recent years, has also begun to emerge in the treatment of mild to moderate psoriasis, and its curative effect is even better than that of biological drugs.
In the field of psoriasis biopharmaceutical therapy, the TNF inhibitors Humira and Enbrel are absolutely dominant, but because the biosimilants of the above two drugs have been listed, their lower prices may cause no small impact on the brand drug market; the IL-23 inhibitor family is also a competitor that cannot be ignored in this field. Among them, IL-12/IL-23 inhibitors of First-in-Class drug Stelara, IL-23 inhibitors Ilumya and Tremfya are typical representatives. It is worth emphasizing that IL-17 inhibitors are also a rising star in the field of psoriasis treatment.
6. Peanut allergy new drug: AR-101
Peanut allergy is one of the most common potentially life-threatening food allergies, affecting about 6 million people in the United States and Europe alone. At present, there is no therapeutic drug for peanut allergy in clinical practice. What people at risk can do is to avoid contact with peanuts as much as possible. If you accidentally produce an allergic reaction, you need to inject epinephrine in time.
Aimmune company's AR-101 is an oral drug that contains a certain amount of peanut protein. In order to desensitize patients to peanut protein and induce patients to improve their tolerance to peanuts, the dose of the drug should be gradually increased in the first few months, and when the dose reaches a certain level, the drug should be maintained to maintain the tolerance to peanuts.
In December 2018, the Aimmune submitted a AR-101 application to the FDA for marketing to alleviate peanut allergy in children and adolescents aged 4 to 17 years old, and applied for a "priority review". The Cortellis team predicts that the AR-101 will be approved in the United States in November 2019, with a 95% approval success rate.
Although some studies in recent years have shown that oral immunotherapy can induce human tolerance to food allergy, it is about to become the first-in-class AR-101 in this field, and the market potential should not be underestimated. The Cortellis team predicts that AR-101 sales will top $1.17 billion in 2023.
The competition of AR-101 mainly comes from two aspects: on the one hand, other peanut desensitization therapy in the research and development stage is the inevitable competitor of AR-101. Among them, DBV Technology's "Viaskin Peanut transdermal therapy" is a typical representative of this type of drug. In October 2018, DBV Technology submitted a marketing application to the FDA for the treatment of peanut allergy in children aged 4 to 11 years. However, the FDA concluded that the company submitted insufficient data on manufacturing processes and quality control. Following discussions with the FDA, the company withdrew the listing application in December 2018 and initiated preparations for the resubmission process. The Cortellis team predicts a 26% success rate for Peanut approval in Viaskin.
On the other hand, oral immunotherapy is also a potential competitor to AR-101. Among them, ProTA's probiotics and peanut oral immunotherapy (PPOIT) and Camallergy's oral peanut immunotherapy (CA-002) are well-known. Up to now, these two therapies are in the phase III clinical trial preparation stage.
7. β-thalassemia new drug: LentiGlobin
Beta thalassemia is a hereditary disease that is a life-threatening anemia caused by a decrease or deficiency of beta-globin (half of the hemoglobin complex). Patients with severe beta-thalassemia may require regular blood transfusions throughout their lives, but repeated blood transfusions in patients can lead to iron overload, which can further lead to extensive organ damage. Therefore, patients who are regularly transfused clinically must be further treated with iron chelation therapy. The incidence of the disease varies widely around the world, with about 60000 children born each year.
Allogeneic hematopoietic stem cell (HSC) transplantation is the main treatment for transfusion-dependent β-thalassemia. Due to the introduction of allogeneic genes, this treatment is very risky. Clinically, the treatment usually requires the donor's stem cells to be highly compatible with the patient's genes and tissues (usually the donor is derived from siblings).
The LentiGlobin by Bluebird Bio offers another option for the treatment of the disease. The therapy begins with taking the patient's own cells, genetically modifying them to produce functional beta-globin, and then reintroducing the modified cells into the patient's body.
There are many potential mutations in the β-globin gene. Among them, a mutation that reduces β-globin production is called β, and a mutation that prevents a gene from producing β-globin is called β0. If the patient has a complete β0 mutation (homozygous β0: "β0/β0"), the body cannot produce β-globin.
For patients with transfusion-dependent β-thalassemia, the LentiGlobin marketing strategy is to use the "non-β0/β0" genotype as a breakthrough (I. e., patients with some β-globin residues). In October 2018, the European Union accepted the registration of the drug for the treatment of "non-beta 0/beta 0" adolescents and adults.
The Cortellis team predicts that the LentiGlobin is expected to be approved in the EU in November 2019, with an approval success rate of 88%. In the United States, the drug is expected to be approved in February 2021, with an approval success rate of 70%. In terms of the market, sales in LentiGlobin are expected to exceed $1.12 billion in 2023.
In terms of market competition, drugs with the same mechanism of action as LentiGlobin are currently lagging behind LentiGlobin. The most famous of these is the OTL-300 of Orchard, which is currently in Phase II clinical trials. The Cortellis team predicts that the OTL-300 is expected to be approved in the EU in 2023, with an approval success rate of 70%.
In addition to "beta-globin gene repair", other mechanisms of action of transgenic stem cell therapy is also a potential competitor to LentiGlobin. For example, "BCL11A gene modification", by modifying the gene to relieve the inhibition of BCL11A gene, patients with beta thalassemia or sickle cell anemia can produce enough hemoglobin on their own. The CTX-001 jointly developed by Vertex and CRISPR is a typical representative. The current clinical trials of the drug are mainly focused on two indications: "beta thalassemia" and "sickle cell disease". At present, both trials are in phase I/II clinical trials. Coincidentally, Sangamo and Bioverativ ST-400 have also entered the beta thalassemia phase I/II clinical trial in May 2018.(Contributed by Corey Weian and translated by Ma Lewei)