Crowned by a potential cure for severe hemophilia A, that could become the most expensive drug ever, a new list of 11 medicines expected to generate $1 billion-plus in annual sales by the end of 2024 or earlier throws into stark relief the growing tension between medical innovation and society's ability to pay for it. The 2020 Cortellis Drugs to Watch list, including medicines both approved and likely to be, points to a future of ongoing conflict between payers and industry spurred by fundamental disagreements.

Drugs for central nervous system indications and cancer comprise much of the list, developed by Clarivate Analytics' Cortellis forecast team. Almost universally, they have been accelerated in their development by orphan drug status or other designations intended to spur closer cooperation between regulators and drug developers with the intention of speeding their availability for patients. The 11 likely blockbusters identified collectively hold 18 orphan drug designations, four FDA breakthrough therapy designations, two EU PRIME designations and a Japanese SAKIGAKE designation.

Drugs considered in the analysis had advanced to phase II trials or beyond by early 2020. Medicines launched prior to 2020 were excluded. Listed drugs that are not yet approved are expected to go to market in 2020, based on factors such as companies' expected approval or launch dates.

Most medicines on the list are entering or are poised to enter indications already crowded with competitors, meaning they'll face substantial pressures to differentiate themselves. Many are expected to tout improved safety vs. alternative therapies, especially around cardiovascular risk, while others will seek to highlight novel mechanisms of action or even curative potential.

Two of the medicines, Rybelsus (oral semaglutide) and Enhertu (trastuzumab deruxtecan) have already won U.S. regulatory approvals, each heralding significant new innovations to justify their potential value to patients and payers. Rybelsus, from Novo Nordisk A/S, represents the first oral glucagon-like peptide-1 receptor agonist for people with type 2 diabetes, capturing the benefits of a medicine that had until now only been available as an injectable medicine in a more convenient once-daily tablet. Enhertu, a medicine from Daiichi Sankyo Co. Ltd. and Astrazeneca plc approved months ahead of expectations, delivered a new method for targeting certain breast tumors, building on the many advances in medicine's understanding of the diseases since the approval of another blockbuster, Herceptin (trastuzumab, Roche Holding AG) in 1998.

More than half the medicines on the list are biologics, a fast-growing and increasingly expensive segment of prescription medicine for which regulators and payers alike have sought to rein in costs during recent years, albeit with differing approaches. Gene and cell therapies – represented on this year's list by hemophilia A therapy Valrox (valoctocogene roxaparvovec, Biomarin Pharmaceutical Inc.) and lisocabtagene maraleucel (Bristol-Myers Squibb Co.) for large B-cell lymphoma, respectively – have drawn particular attention for their budget-busting potential, especially in the wake of 2019's eye-opening price for Zolgensma (onasemnogene abeparvovec), a therapy for the rare genetic disease spinal muscular atrophy. Featured on the 2019 Cortellis Drugs to Watch list, Zolgensma debuted in May 2019 with wholesale acquisition cost of about $2.1 million.

Though welcoming innovative biologics, regulators have also sought to encourage greater price competition for older products in the class from biosimilars. Biosimilars are medicines deemed to be highly similar to a reference biologic already approved. Such challengers could pose headwinds for several entrants on this year's Cortellis Drugs to Watch list, including ozanimod for multiple sclerosis (Bristol-Myers Squibb Co.) and filgotinib for rheumatoid arthritis (Galapagos NV and Gilead Sciences Inc.)

Despite public outrage over prescription drug prices in the U.S. and political efforts to address it, such as the Lower Drug Costs Now Act (H.R. 3), bitter partisan divides in Washington an often-opaque mix of players keen to protect the status quo continue to stand in the way of progress. Meanwhile, American efforts to assess the value of medicines vs. their cost have often met with hostility from drugmakers wary of developments in other major markets, where governments have pressured their ability to reap the kind of profits they often seek in the U.S.

With 11 entrants, this year's Cortellis Drugs to Watch list is both numerically longer than last year's seven-drug list and includes more first-in-class medicines. Biohaven Pharmaceutical Holding Co. Ltd.’s rimegepant (BHV-3000) for migraine is positioned to become the first small molecule CGRP antagonist to launch for acute treatment of migraine. Valrox, if approved, would become the first gene therapy for any form of hemophilia. Inclisiran, from The Medicines Co. (recently acquired by Novartis AG), could become the first siRNA-based inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) to win approval. And Immunomedics Inc.’s sacituzumab govitecan is poised become the first antibody-drug conjugate to target TROP-2, a pan-epithelial cancer antigen.

Highlighting the importance of even small deviations in each drug's path to market, last year's sole first-in-class medicine on the list, Aimmune Therapeutics' Palforzia (peanut), wasn't even approved until Jan. 31, 2020, and now isn't expected to exceed $1 billion in sales until 2024, a year later than previously thought. Sales of other past Cortellis Drugs to Watch have either languished, like Takhzyro (lanadelumab, Takeda Pharmaceutical Co. Ltd.) for the prevention of hereditary angioedema, or soared, such as with the hemophilia A medicine Hemlibra (emicizumab, Roche Holding AG).

No matter the fate of the drugs on this year's list, it’s likely that the messy tension among scientific innovation, commercial motive and public goods will continue to be top of mind in the year ahead, as medical research and the pursuit of innovative medicines continues to accelerate.

More specific analysis

BioWorld brings into focus each of the 11 therapies via additional articles and infographics found at https://www.bioworld.com/drugstowatch2020.

A few highlights of these insightful articles include:

  • Inclisiran’s inclusion on this year’s Cortellis Drugs to Watch list is an example of target discovery possibilities hiding in plain sight – if companies and institutions are willing to put effort into increasing sample diversity in genomic research.
  • Antibody-drug conjugates ‑ often dubbed guided missiles ‑ for many years failed due to the complexity of pairing the right antibody with the right toxic agent. On the blockbuster list are two (sacituzumab govitecan and Enhertu), which implies that the technology is finally maturing.
  • William Kaelin Jr.’s Nobel Prize-winning scientific discoveries on how cells sense and adapt to oxygen availability have proved to be both top-rate science, and very translatable indeed, ultimately enabling the development of multiple therapies targeting anemia and cancer, including vadadustat.

A voice for patients

In addition to the deep dive into the drugs, the companies backing them and the competitive landscapes, this year we look to the patients who might benefit from and pay for these new therapies.

Read about Karen Jury, diagnosed in 2007 with relapsing-remitting multiple sclerosis (MS). In the time since, she has marched through a parade of trial-and-error therapies. Will two new MS drugs make a difference in her life?

For familial hypercholesterolemia (FH) patients, the demand for new options matters, according to Katherine Wilemon, founder and CEO of the FH Foundation, a patient advocacy group. If approved, inclisiran will be the first and only cholesterol-lowering siRNA product. It’s personal for Wilemon, who lives with FH and suffered a heart attack at age 39. That’s when she discovered her oldest daughter has the disease, too. “If we can crack this nut, we’ll be able to prevent a lot of cardiovascular disease” caused by FH, which is “hiding in plain sight,” she said.

Jaime Sanders was just a child, barely eight years old, when chronic migraines kept her inside from recess and home from school. She’s spent a lifetime trying new drugs to treat the debilitating condition. With 15 down days a month, she was forced to quit her job. The prospect of trying yet another drug, rimegepant, is both encouraging and daunting because she worries her insurance company won’t pay for it.

Editor’s note: The list and a compendium of articles covering the analysis are freely available online at: www.bioworld.com/drugstowatch2020