10. Takeda

Takeda HQ
As divestments focused on some noncore assets continue into 2021, Takeda is turning its attention to a "Wave 1" of pipeline drugs that it hopes could bring in more than $10 billion in combined peak sales. (Takeda)

2020 revenue: JPY 3,127.5 billion ($29.25 billion)
2019 revenue: JPY 3,236.7 billion ($30.27 billion)
Headquarters: Tokyo, Japan

In 2020, Takeda hit the $10 billion product selloff goal it had previously set as a way to reduce the debt load incurred from the Shire acquisition. But as a company spokesperson noted, it’s a target, not a cap.

For divestment, Takeda has been targeting drugs that fall outside of its key focus areas: neuroscience, gastroenterology, oncology, rare diseases and plasma-derived therapies. At the same time, the company has been working to expand the market for established drugs and boost its pipeline.

The Japanese pharma sold select consumer health and non-core products in Latin America to Brazil’s Hypera Pharma for $825 million. And it offloaded 18 over-the-counter and prescription drugs in the Aisa-Pacific region to South Korea’s Celltrion for $278 million. Takeda also sold off products to Germany’s Cheplapharm, Danish company Orifarm and TachoSil.

In its home country, Takeda ditched its Japanese consumer health portfolio, giving the franchise to a company controlled by Blackstone for JPY 242 billion ($2.3 billion).

Those deals had already pushed Takeda pass the $10 billion target, but the company didn’t stop there. It also transfered some cardiovascular and metabolic drugs in the Chinese mainland to local government-backed Hasten Biopharmaceutic and licensed out seven R&D programs in its neurology pipeline to Neurocrine Biosciences.

Thanks to those deals—some of which have not closed to be counted in financial reports—Takeda reduced its net debt/adjusted EBITDA ratio to 3.6x at the end of 2020, moving closer to its deleveraging goal of 2x by fiscal year 2023, which ends in March 2024. And the divestment spree appears very much active heading into 2021.

RELATED: Takeda to transform into a 'cloud-first company' through Accenture, AWS partnership

Takeda's focus on finding new growth opportunities in prescription drugs focused largely on top seller Entyvio for ulcerative colitis and Crohn's disease. For the calendar year 2020, Entyvio hauled in JPY 403 billion ($3.77 billion), up 21.5% year over year.

In May, Takeda snagged an EU nod for an under-the-skin formulation of Entyvio, which allows it to be given at home instead of at the hospital. The FDA in late 2019 handed that formulation a surprising complete response letter with questions related to the design and labeling of its subcutaneous device. The drugmaker talked to the FDA in August and now expects it could launch the new version in the U.S. in 2022.

Takeda’s oncology portfolio chalked up both wins and losses in 2020. Alunbrig got the U.S. green light to reach patients with previously untreated ALK-positive non-small cell lung cancer. Problem is, with calendar 2020 sales at JPY 8.6 billion ($80 million), it’s still well behind 'Roche’s market-leading blockbuster Alecensa. And Pfizer’s third-generation ALK inhibitor, Lorbrena, just broke into the front-line setting with arguable the best efficacy data.

But Takeda's blood cancer drug, Velcade, continued its sales decline stemming from a loss of market exclusivity. Its JPY 75.9 billion ($720 million) sales from April to December marked a 16.4% decrease over the same period in 2019.

The company hopes the gap will be filled by growth from some newer cancer meds such as Velcade follow-on drug Ninlaro, Seagen-licensed antibody-drug conjugate Adcetris, leukemia therapy Iclusig and ALK lung cancer med Alunbrig.

Ninlaro did record one failure, however, in previously untreated multiple myeloma patients who are ineligible for stem cell transplant. A phase 3 trial showed that adding the Takeda drug to a combination of Bristol Myers Squibb’s Revlimid and the steroid dexamethasone didn’t significantly extend the period time before disease progression.

RELATED: Takeda's Ninlaro swings and misses in newly diagnosed myeloma

Like many other biopharma companies, Takeda channeled some of its R&D resources to the search for COVID-19 remedies. For the Japanese pharma, the headline work centered on a hyperimmune globulin product dubbed CoVIg-19 that’s made by concentrating donated plasma from patients who’ve recovered from COVID-19. Takeda is developing the therapy through an alliance co-led by plasma industry leader CSL. The NIH moved the drug into a phase 3 trial among hospitalized patients in October, but enrollment has been slow.

In addition, Takeda is testing its hereditary angioedema drug Firazyr and an intravenous formulation of its follow-on drug Takhyzro in two phase 3 platform trials. The hope is that one of these two drugs can help contain dangerous inflammatory responses in some COVID patients.

What’s more, Takeda has signed on to help vaccine developers to bring their COVID shots to Japan. It will help distribute Moderna’s mRNA vaccine, and will develop, manufacture and sell Novavax’s NVX-CoV2373 in Japan.

RELATED: Beyond COVID-19: The top vaccine programs to watch in 2020 | Takeda, Dengue fever

Also on the vaccine front, Takeda plans to file soon for approval of its dengue fever shot, TAK-003. It’s among a dozen new drugs Takeda aims to launch by fiscal year 2024 that it said could bring in combined peak sales of more than $10 billion.

An application for TAK-721, an oral suspension form of corticosteroid budesonide, in the inflammatory disease eosinophilic esophagitis has been awarded FDA priority review. Also on the “Wave 1” R&D list is maribavir, which recently succeeded in a phase 3 trial in transplant recipients with refractory cytomegalovirus (CMV) infection.

10. Takeda