2021: Highlights in Drug Launches

The past year has seen tremendous advances in drug discovery, with accelerated pipelines and novel breakthrough medicines featuring throughout. Unsurprisingly, novel vaccines and antiviral treatments tailored against COVID-19 have made for flashpoint news over the last year, showcasing the progress the industry has made in an effort to combat one of the most urgent crises in recent history. These efforts have spurred growth in other areas of the life sciences as well, re-affirming the old adage that necessity is the mother of invention. This article will explore the most promising novel agents discovered in 2021.

Coronavirus

The first mention naturally has to go to new efforts being developed to tackle SARS-CoV-2. With 95 vaccine candidates and 25 vaccines approved for use in different jurisdictions, the field has made colossal progress in the span of just two years. While no new vaccines entered the market this year, we have seen growing acceptance of findings regarding the safety of existing vaccines in even younger populations, as well as a wider recognition of the Russian Sputnik V, the Chinese Sinovac and the Indian Covaxin jabs. As discovery candidates continue to emerge and the need for a broader range of vaccines to counter variant evolution becomes apparent, we expect the field to continue unabated in the next year. The insights gleaned from the development of COVID vaccinations have already given a tremendous boost to other vaccination efforts.

Molnupiravir and paxlovid, developed by Merck and Pfizer respectively, are the first oral anti-virals to be approved for use against COVID-19 to limit symptomatic disease and decrease hospitalization rates. Further developments included research on new monoclonal antibodies, such as wider adoption of Regeneron’s Casirivimab/imdevimab combination and the approval of GSK’s Sotromivab. Immunomodulators also saw widespread approval, following findings that the reduction of immune inflammation can lessen the clinical impact of the disease – such as Baricitinib by Eli Lilly and Tocilizumab by Roche. The vast chemical space being explored through this multi-pronged approach at lessening the impact of COVID-19 has given new applications of life to older classes of drugs and is also indicative of the rising importance of antiviral and biologic treatments.

Oncology

This year has seen a number of breakthrough approvals for anti-cancer therapies, particularly in the area of immuno-oncology. One of the highlights has been the progress of agents for the treatment of non-small cell lung cancer, targeting the KRAS protein which was once thought to be an undruggable target. The first to gain approval was  Sotorasib by Amgen; a breakthrough designation was also granted to Adagrasib by Mirati Pharmaceuticals, although it has yet to obtain approval. While Adagrasib shows a deeper level of anti-tumour activity, Sotorasib shows a greater degree of safety. However, Adagrasib also exhibited promising activity against colorectal cancers.

As the agents established the viability of monotherapies that target KRAS, 2021 also saw the investigation of combination therapies involving the protein – with Amgen and Mirati currently locked in a race to announce positive combination trial reports. As we move to 2022, more companies seek to advance their KRAS inhibitors to further trials, including Novartis, Genentech/Roche, Johnson & Johnson, Jacobio Pharmaceuticals, Boehringer Ingelheim and others. The developments regarding KRAS show the potential of immunotherapies moving towards the solid tumour space – as they have already proven their use against haematological malignancies. 

Human Immunodeficiency Virus (HIV-1)

In keeping with advancements in antivirals, 2021 saw the approval of a combination of cabotegravir and rilpivirine, marketed as Cabenuva by ViiV Healthcare. HIV is perhaps the virus that is most responsible for the large growth in antiviral research over the last few decades – and continues to receive outsized focus given the large burden it poses worldwide and our inability to cure it. Treatment up to now involved the administration of daily antiviral pills – usually a combination of three agents. This presents challenges in adherence, both from a patient standpoint but also on a logistical level. Cabenuva revolutionised this status quo by virtue of it being a long-acting injectable which only needs to be administered once a month; it is expected that this will make living a full, normal life with HIV even easier than before. GlaxoSmithKline, the majority owner of ViiV Healthcare, expects the market for its long-acting injectable to be valued at over £2b by 2026.

Alzheimer’s Disease

Perhaps no other drug will have had as much of a roller coaster year as Biogen’s aducamunab. Widely anticipated by patients and the industry, nobody expected aducamunab to be a wonder treatment. But the modest improvements it promised over the current dearth of therapeutics were something, even if it was accompanied by a host of adverse effects. The drug received its approval, documented in our earlier coverage here, through a fast-tracked process. Controversy soon followed regarding the interactions between Biogen and the FDA that led to approval, as well as the real-world efficacy and side effects of the drug, which we also covered here. Whatever happens to the future of aucamunab, however, the flashpoint it created in 2021 will serve as a stark reminder of the need for improved standards of care and treatment in Alzheimer’s Disease.

African trypanosomiasis

Providing a direct contrast between the accelerated efforts to combat SARS-CoV-2 with rarer, neglected diseases, is the development cycle experienced by fexinidazole. Fexinidazole was first described in 1978; it only received FDA approval this year in 2021, despite being the only all-oral treatment available for sleeping sickness (African trypanosomiasis) caused by Trypanosoma brucei gambiense. Its efficacy is well-documented, and its fast-acting 10 day treatment can provide great relief if the disease has not yet progressed to a severe stage. It may also be active against other types of pathogenic protozoans, with further investigations underway. The evolution of coronavirus and the increasing threat of zoonotic disease shows that we cannot afford to allow ourselves to become complacent with neglected diseases, and the approval of fexinidazole has been long overdue. 

Autoimmune disorders

In 2021, we also saw the approval of first-in-class treatments for a number of auto-immune diseases. One such approval was for anifrolumab for Lupus erythematosus, marketed as Saphnelo by AstraZeneca. Anifrolumab was the first new treatment to be approved for systemic lupus erythematosus in over ten years, as well as the first type I interferon agonist to be approved altogether – underscoring the importance and innovation involved in the decision-making. The drug not only improves symptoms in patients, but also improves outcomes by reducing the overall corticosteroid requirements. 

Another autoimmune disorder which has seen a revolutionary approval this year has been Myasthenia gravis, with the approval of efgartigimod, marketed as Vyvgart by Argenx. Efgartigimod represents the first treatment to directly target the disease – current options were limited to surgery, steroids and chemotherapy. The drug prevents the recycling of immunoglobulin G (IgG) back into the blood, resulting in lower overall levels of IgG by blocking the neonatal Fc receptor. 

Conclusions

Looking forward, there are no doubt multiple developments regarding further treatments and vaccines for COVID-19 in 2022 – the pandemic remains as relevant as ever, particularly by its omicron-fuelled resurgence. The last year has seen tremendous progress in revolutionary products across a slew of areas of medicine. While oncology occupies a regularly prominent position in drug approvals, the novel treatments we have seen this year show the new potential of immunotherapies – which we have also seen applied to the field of autoimmune disorders, a field in dire need of innovation. 

Nick Zoukas, Former Editor, PharmaFEATURES