2. Roche

Biosimilars to Herceptin, Avastin and Rituxan bit off a bigger-than-expected piece off Roche's topline in 2020. (Roche)

2020 revenue: CHF 58.32 billion ($62.05 billion)
2019 revenue: CHF 61.47 billion ($65.40 billion)
Headquarters: Basel, Switzerland

Roche’s megablockbuster cancer troika—Herceptin, Avastin and Rituxan—officially faced off U.S. biosimilars for the first full year in 2020. And the result was bloodier than most had expected.

At the beginning of 2020, Roche was expecting biosimilars to bite roughly CHF 4 billion off its franchise, including an erosion in EU and Japan similar to the CHF 1.2 billion it had suffered in 2019. However, by the end of the year, the worldwide loss amounted to CHF 5.7 billion, including CHF 5.05 billion from the U.S., EU and Japan.

That’s probably the worst it can get, though, Roche’s pharma chief Bill Anderson said during the company’s fourth-quarter earnings call in February. In 2021, it expects a biosims hit of CHF 4.6 billion, he said.

RELATED: Roche hit by worst-case biosim assault—to the tune of $5.6B—as COVID-19 hurts new king Ocrevus

Despite U.S. biosimilars being a bigger-than-expected threat, as CEO Severin Schwan described it, the company would have been able to compensate for the revenue gap with growth from newer drugs if it hadn't been for COVID-19. But the reality was, Roche’s drugs—most of which are injectables administered by healthcare professionals—underperformed during the pandemic as patients and potential patients avoided doctor visits.

Multiple sclerosis drug Ocrevus became Roche’s new best-selling drug starting from the third quarter of 2020. But its full-year sales haul of CHF 4.48 billion fell below industry watchers’ expectations, and its 24% year-over-year growth at constant currencies was clearly a slowdown from 2019’s 57%.

In a scary trend that Anderson said could continue for years to come, Ocrevus suffered from major quarterly fluctuations thanks to the pandemic. In the second quarter, when COVID-related restrictions were at their tightest, Ocrevus failed to attract new, switching patients, and some existing patients delayed treatment as they feared the drug’s B cell-targeting mechanism might hurt their immune defense against the coronavirus. Because the injectable drug is given every six months, the sudden stagnation in Q2 extended to Q4, and that cycle could last for years, Anderson explained.

PD-L1 inhibitor Tecentriq represents another key growth engine for Roche, with 2020 sales at CHF 2.74 billion after an increase of 55% at unchanged exchange rates. The drug achieved several milestones last year, including U.S. approvals in newly diagnosed non-small cell lung cancer and for use in combination with Avastin for previously untreated liver cancer. It had some wins and fails in clinical development. These include trial flops for a cocktail with Pfizer and Astellas’ Xtandi in bladder cancer; in post-surgery muscle-invasive bladder cancer; and in ovarian cancer.

RELATED: ESMO: Roche's mixed results put Tecentriq's triple-negative breast cancer use into question

In the brand-new drug category, Roche added three FDA approvals to its U.S. portfolio and was preparing to do the same for a couple of late-stage assets.

In July, the Swiss pharma paid $775 million upfront for Blueprint Medicines’ RET inhibitor pralsetinib, on the heels of Eli Lilly winning an FDA nod for rival med Retevmo. Pralsetinib snagged its FDA go-ahead under the brand Gavreto in RET-altered NSCLC in September and added thyroid cancer in December, matching up to Retevmo’s label.

Evrysdi launched into the crowded spinal muscular atrophy market, and analysts believe its oral dosing and relatively low cost could help it steal meaningful share from Biogen’s market leader Spinraza. Meanwhile, also in the neuroscience department, Roche nabbed U.S. approval for Enspryng for neuromyelitis optica spectrum disorder.

RELATED: Roche's low-price Evrysdi will take 'meaningful' SMA share from Biogen's Spinraza: analyst

Down the R&D line, there’s a Lucentis follow-on drug, VEGFxAng2 bispecific antibody faricimab, which recently matched Regeneron’s blockbuster Eylea in phase 3 trials in diabetic macular edema and wet age-related macular degeneration. Roche shelled out $120 million for rights to a UCB anti-tau antibody for potential use in Alzheimer’s disease, while remaining cautious about its own gantenerumab, a beta-amyloid antibody that has failed before but are still being evaluated in two phase 3 studies.

Gavreto and UCB’s UCB0107 were among 92 new agreements Roche’s pharma division signed in 2020. Perhaps one better-known deal is its 2020 agreement to produce Regeneron's COVID-19 antibody cocktail REGN-COV2 and launch it in the EU. The therapy has since won FDA authorization for patients with mild-to-moderate disease at risk of severe illness. Regeneron is also positioning the therapy as a potential “passive vaccination” to help prevent the disease in people exposed to family members with COVID.

RELATED: Roche, Regeneron join forces to more than triple manufacturing of COVID-19 antibody cocktail

Roche landed in the spotlight of the COVID fight early on when its IL-6 arthritis drug Actemra won a spot on China's treatment guideline based on early signs that it could tamp down a life-threatening immune overreaction called cytokine storm. The drug has turned up mixed results in three Roche-sponsored clinical trials here, here and here. And a recent large-scale trial in the U.K. found both it and Regeneron’s IL-6 inhibitor Kevzara could significantly reduce the risk of death in COVID patients in intensive care. Thanks to its COVID uptake, Actemra sales jumped 32% in 2020 to CHF 2.86 billion.

Other COVID-19 products boosted Roche Diagnostics division, fueling 14% growth last year at constant currencies despite a decline in some routine tests. Altogether, the Swiss company launched 15 diagnostics for COVID in 2020. In contrast, the larger pharma division posted a sales decrease of 8%—or 2% at constant currencies—to CHF 44.53 billion.

2. Roche