Orphan drugs and breakthrough therapies dominate the list of seven drugs predicted to launch this year and forecast to achieve blockbuster status by 2023, according to the Cortellis Drugs to Watch 2019 report, from Clarivate Analytics.
Since 2013, the Cortellis team has applied its proprietary technologies, tools and techniques to produce its Drugs to Watch report. Each edition showcases drugs entering the market that year with the potential to become blockbusters within five years. A blockbuster drug is defined by $1bn in annual sales.
There are three common themes among the seven drugs for 2019.
First is diverse competition. The drugs highlighted in the report will face a variety of competitive landscapes in the markets they aim to enter, ranging from a single strong opponent to a plethora of different agents, each with its own strengths and weaknesses.
Second is the dominant therapeutic areas. The list almost fully comprises agents targeting genetic disorders or aberrant immune responses. The ability to not only define but also to manipulate underlying mechanisms of disease is a hallmark of these drugs, and attests to the remarkable progress of medical and scientific knowledge in recent decades.
The third theme is niche versus mass clinical impact. A high proportion of this year’s list addresses rare and orphan diseases, with all seven drugs achieving at least one regulatory designation in at least one country, including:
- Nine US, four EU and one Japanese Orphan Drug designation
- Four US Breakthrough Therapy designations
- Two EU PRIME designations
- One US Regenerative Medicine Advanced Therapy designation
- One Japanese Sakigake designation
- One Chinese Priority Review.
Interestingly, this year’s list contains no cancer drugs.
However, this does not indicate a downward trend in the focus on cancer. Rather, it may reflect the increasing range of new oncology treatments in development, resulting in a smaller potential market share for each one, thus decreasing the likelihood of any particular drug becoming a blockbuster. Furthermore, the expansion into new oncology indications for established drugs does not fall within the remit of this report, which focuses on drugs that are new to the market.
The Drugs to Watch report is produced using a range of information, analytics and expertise available in Cortellis. This year’s report additionally features insight from the new Cortellis Analytics – Drug Timeline & Success Rates module, an analytic that predicts the probability of launch and timeline to market for ongoing drug projects.
The Cortellis Drugs to Watch 2019 report examines the seven treatments identified, along with analysis of the competitive and market dynamics each is expected to face ahead. Here is a quick profile of each drug featured, including notes on their regulatory journey:
Upadacitinib, from AbbVie, treats rheumatoid arthritis. Upadacitinib is an orally dosed inhibitor of an intracellular target called JAK1. Dysfunction in the regulation of the JAK family of molecules is implicated in the aberrant production of pro-inflammatory mediators that are involved in the pathogenesis of rheumatoid arthritis, and inhibition of JAK proteins is an established method of controlling the symptoms of this disease.
Upadacitinib was filed for approval in the US and EU in December 2018 and accepted for US Priority Review in February 2019. The sales forecast for upadacitinib for 2023 is $2.20bn.
Zolgensma (onasemnogene abeparvovec), developed by AveXis, is an injectable gene therapy that uses a viral vector to introduce DNA that corrects the genetic defect underlying spinal muscular atrophy (SMA). The Novartis subsidiary sought approval via both Orphan Drug and Breakthrough Therapy designations.
In the third quarter of 2018, AveXis filed Zolgensma for approval in the US, EU and Japan for the treatment of SMA type I. The company expects 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. The sales forecast for Zolgensma is $2.09bn.
Roxadustat, from AstraZeneca, FibroGen and Astellas, targets anaemia in chronic kidney disease (CKD). The first-in-class inhibitor of hypoxia- inducible factor-prolyl hydroxylase, or HIFPH, was approved in December 2018 in China for the treatment of CKD-related anaemia 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 anaemia in CKD patients on dialysis was submitted in October 2018. A US filing is expected in the third quarter of 2019. The forecast for 2023 sales is $1.97bn.
Ultomiris (ravulizumab), from Alexion, treats paroxysmal nocturnal haemoglobinuria, a rare, potentially fatal blood disorder. It is a next- generation follow-on to Soliris, Alexion’s current PNH blockbuster – also a humanised monoclonal antibody – with more convenient dosing.
Ultomiris received approval as an Orphan Drug from the FDA for adult patients with PNH in December 2018, just six months after the drug was filed, and two months ahead of the FDA’s target date for the completion of Priority Review. It was launched in the US in January 2019, making it the first of the 2019 Drugs to Watch to reach the market. In the EU and Japan, approval of the drug is pending, following acceptance of regulatory filings in 2018. Sales are projected at $1.93bn for 2013.
Skyrizi (risankizumab) treats psoriasis. Developed by Boehringer Ingelheim and AbbVie, Skyrizi is a monoclonal antibody that inhibits the pro-inflammatory cytokine IL-23. It will compete with numerous treatment modalities, including entrenched biological agents and biosimilar biologicals.
It gained US approval for moderate to severe plaque psoriasis in April, and for EU approval in that indication in early May. In May last year, approval for Skyrizi was filed in Japan for plaque psoriasis, psoriatic arthritis, pustular psoriasis and erythrodermic psoriasis. Forecast sales for Skyrizi in 2023 are $1.74bn.
AR-101 from Aimmune Therapeutics addresses peanut allergy. Designated as a Breakthrough Therapy, AR-101 is an oral drug containing peanut antigen.
A regulatory filing for US approval of AR-101 in children and adolescents aged from 4 to 17 years was submitted in December 2018, with a request for Priority Review. However, Aimmune reported in February 2019 that the FDA had initially determined that the drug, as an allergenic extract, was exempt from the PDUFA process. This determination may mean that instead of expedited review because of AR-101’s Breakthrough Therapy designation, the filing may be given a 12-month target period. Discussions were underway between the FDA and the company regarding the review timeline. An EU filing is expected in the first half of 2019. With a first-in-class therapy with no competition expected soon, sales for 2023 are forecast at $1.17bn.
LentiGlobin (betibeglogene darolentivec), an Orphan Drug and Breakthrough Therapy from Bluebird Bio, corrects the defect causing beta thalassemia, a blood disorder that causes life-threatening anaemia. Its only immediate competition will be donor stem cell transplants, which carry significant patient risks. LentiGlobin provides an allogeneic alternative to autologous transplants. Instead of using donor cells, the patient’s own cells are harvested, genetically modified to produce functional beta-globin, and then infused back into the patient.
The initial studies for LentiGlobin in transfusion- dependent beta thalassemia have focused on patients with non-beta0/beta0 genotypes; that is, patients who have some residual production of beta globin. The gene therapy gained recommendation from the EMA’s CHMP in March for non-beta0/beta0 adolescents and adults. It is currently in phase 3 in the US. The sales forecast for 2023 are $1.12bn.
Overall, the seven Drugs to Watch for 2019 are impressive products, and it will be of great interest to watch their progress throughout 2019 and beyond. Covering a wide range of conditions, and with the recurring themes of genetic modification and immune modulation, they represent a fascinating snapshot of the cutting-edge development that characterises the medical life sciences industry today. Together, they boost the outlook for several companies and partners, while bringing hope to patients dealing with some of the most intractable diseases.