36-37 - Drugs to watch - Class of 2021

Despite the need to pivot to development of much-needed SARS-CoV-2 vaccines and treatments, biopharma companies successfully continued developing drugs and biologics that fill treatment gaps for tens of millions of patients worldwide. Some have the potential to reach blockbuster status (annual sales >$1 billion within five years), marking them as drugs to watch, including therapies for Alzheimer’s disease, psoriasis, prostate cancer, endometriosis, uterine fibroids and congestive heart failure.

Every year since 2013, Clarivate has identified the treatments that are likely to reach blockbuster status based on analysis of its life sciences solutions and integrated data sets that span the R&D and commercialisation life cycle. Only drugs in Phase II or III trials, at pre-registration or registration stage, or already launched in early 2021, including already approved drugs launched for a new indication that could be particularly impactful on the industry are considered. A global team of analysts, spanning a plethora of therapeutic areas evaluated each drug based on factors such as expected approval or launch dates, competitive landscape, regulatory status, trial results, market dynamics and other factors.

The four drugs selected (based on the data available as of January 21, 2021) are aducanumab, bimekizumab, relugolix (Orgovyx) and vericiguat (Verquvo). They represent a rather conservative list, when compared with previous lists, that partly reflects a trend toward specialty drugs with narrow initial indications that gradually expand into other indications over time. However, these treatments have great potential to not only reward shareholders and fund future innovation but also improve or save patient lives and redefine standards of care within their therapeutic areas.

Developed by Biogen Inc and Eisai Co Ltd, this recombinant chimeric human IgG1 mAb targeting beta-amyloid holds great promise for the millions of people affected by Alzheimer’s disease (AD) globally. As the first putative disease-modifying therapy (DMT) for AD to demonstrate a clinical effect in early AD patients in a Phase III study and the first to undergo regulatory review (currently ongoing in the US, Europe and Japan), its approval would represent a major clinical, commercial and regulatory milestone, ending decades of failure in this underserved market that has not seen an approval of a novel drug in more than 15 years.

The current standard of care across mild, moderate and severe AD consists purely of symptom management, based on acetylcholinesterase inhibitors (AChEIs) and memantine, which are now available in generic formulations. In this setting, aducanumab has a large advantage in the market, although there could soon be competition from other key anti-beta-amyloid DMTs that are in late-phase development: lecanemab (BAN2401; Eisai/Biogen) and gantenerumab (Roche).

Approval of aducanumab, however, remains uncertain, given the limitations associated with the data and analysis, and is the key factor affecting its potential as a blockbuster drug. And unknowns exist about overall health system preparedness regarding necessary testing, early diagnosis, reimbursement and administration.

Bimekizumab, a humanised monoclonal IgG1 antibody developed by UCB, is an innovative treatment for psoriasis that provides incremental improvement over existing treatment options, but with significantly fewer side effects. As the first biologic agent that simultaneously targets both IL-17A and IL-17F to enter Phase III studies, it is also being investigated to treat psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), ulcerative colitis and hidradenitis suppurativa.

Whilst the psoriasis market is currently quite crowded with treatment options (including Humira, Embrel, Stelara, Cosentyx, Taltz, Tremfya and Skyrizi), current biologic treatments often fail to result in long-term remission. The clinical trial results for bimekizumab are promising, suggesting best-in-class efficacy. However, its adoption in the market will depend on its long-term efficacy and safety profile. Because of the stiff competition, bimekizumab will be limited to third or fourth-line treatment for patients who have not responded, lost response or experienced unacceptable side effects with other treatments. To reach blockbuster status, it will be critical that it becomes the preferred inhibitor over at least some of three competitors in its class (brodalumab [Siliq], ixekizumab [Taltz] and secukinumab [Cosentyx]).

A GnRH (gonadotropin-releasing hormone receptor antagonist), relugolix offers an effective, oral treatment choice for patients with prostate cancer (approved in the US) or uterine fibroids (approved in Japan) as well as patients with endometriosis once it is approved for this indication. Developed by Takeda Pharmaceutical Co Ltd and licensees Myovant Sciences Ltd, Pfizer Inc, ASKA Pharmaceutical Co Ltd and Gedeon Richter, relugolix represents one of a new class of treatments that could significantly influence patient outcomes and quality of life. Compared with the injectable administration of current GnRH agonist competitors, the oral formulation of relugolix offers greater convenience and better management of side effects.

Although patients with prostate cancer have access to a broad therapeutic armamentarium, which will be expanded by the dynamic late-phase development pipeline spanning a wide range of drug classes, relugolix fills an efficacy gap. Women with endometriosis or uterine fibroids gain a more effective medical management option with fewer menopause-like side effects that might prevent or delay the need for surgical treatment that can result in permanent loss of childbearing capability. However, treatment with relugolix does carry a risk of long-term hypoestrogenic side effects, such as bone loss, that could require management.

The blockbuster potential could be limited by modest uptake due to competition, particularly for prostate cancer, but also as the second-to-market GnRH antagonist for both endometriosis and uterine fibroids in the US, as well as potential hesitance by physicians to prescribe a therapy that could have long-term side effects.

Developed by Bayer AG and Merck & Co, this soluble guanylate cyclase stimulator was approved in the US in January 2021 for the treatment of adults with chronic high-risk, chronic heart failure with reduced ejection fraction (HFrEF) following hospitalisation for HF or receiving outpatient intravenous diuretics.

Review by the European Medicines Agency, Japan’s Pharmaceutical and Medical Devices Agency and China’s National Medical Products Administration is ongoing. This innovative heart failure treatment is the first to be indicated specifically for patients with HFrEF, who are often excluded from clinical trials of other HF treatments and are particularly at risk of re-hospitalisation and mortality.

Other major new drugs recently approved for HFrEF include Entresto (sacubitril/valsartan) in 2015 and Farxiga (dapagliflozin) in 2020, making differentiation necessary for new entrants to be successful. Vericiguat benefits from a distinct mechanism of action, ability to be prescribed as add-on therapy with little risk of severe side effects, once-daily oral dosing and simple titration. Plus, Phase III trial results showed reduced hospitalisation rates and a trend toward reduced cardiovascular mortality in patients with severe, deteriorating HFrEF, which will expand the treatment options for these patients. However, its success in the market could be affected by competition from established drugs, the limited patient population with severe HFrEF and lack of reimbursement.

Beyond the normal market pressures, the impact of COVID-19 on drug development will be long-lasting and influence the introduction of new therapies. Many ongoing clinical trials have been delayed, suspended or terminated; when combined with the substantial decline in new drug and biologic applications and efficacy supplements in 2020, we could see fewer drug launches in 2021. A rapid recovery might be in store if the surge in investment in biotech and biopharma in 2020 heralds a future increase in novel drug launches. Drug development timelines will likely benefit from modifications to the traditional sequential clinical trial model, increased industry collaboration and greater adoption of remote and virtual tools and processes. The effect of current events on the four ‘drugs to watch’ and the potential blockbusters of the future (and the impact on patient care and outcomes) will be of great interest.

CLASS OF 2021