4. Novartis

Novartis
To focus on innovative medicines, Novartis in 2019 spun off Alcon, bought eye drug Xiidra and snatched up The Medicines Company, but its U.S. oral generics business isn't going anywhere soon. (Novartis)

Novartis
2019 revenue: $47.45 billion
2018 revenue: $44.75 billion
Headquarters: Basel, Switzerland

Novartis kept things busy in 2019 as it continued to focus on becoming a top medicines company. It spun off eye care medtech business Alcon, but, at the same time, bought Shire’s Xiidra to boost its ophthalmic drug franchise and acquired The Medicines Company for cholesterol-lowering med inclisiran.

The company touted five new drug approvals with blockbuster potentials last year: the sickle cell treatment Adakveo, eye injection Beovu, multiple sclerosis therapy Mayzent, breast cancer med Piqray and gene therapy Zolgensma. But it also had its fair share of embarrassing moments.

MS drug Mayzent got its FDA nod in March as the first oral treatment with specific label language about its utility in the secondary progressive form of the disease. But Merck KGaA immediately followed with its belated Mavenclad. And in 2019, Mayzent only sold $26 million, a disappointment caused by reimbursement delays and a slower-than-expected process of educating physicians about SPMS, a more severe stage than the relapsing-remitting form.

The MS market is already very crowded. Existing treatments include Novartis’ $3 billion-a-year Gilenya brand and three would-be generic rivals recently approved amid patent litigation. Bristol Myers Squibb just secured clearance to sell oral Zeposia (ozanimod), which belongs to the same S1P receptor modulator class as Gilenya, Mayzent, Mavenclad and Johnson & Johnson’s NDA-ready ponesimod. Biogen has old stalwart Tecfidera and freshly greenlighted Vumerity that comes with better tolerability.

RELATED: Novartis, Merck KGaA and Biogen: Which new MS drug do doctors like best? You might be surprised

Then there's Roche’s anti-CD20 infusion Ocrevus, already a legendary launch story in the MS field. And Novartis could soon have a direct antibody rival in repurposed ofatumumab, now sold as leukemia drug Arzerra, after a trial showed the monthly injection beat Sanofi’s daily pill Aubagio at cutting relapse rates and disability progression.

Still competitive, but not so crowded, is the spinal muscular atrophy field, where Novartis got the go-ahead for gene therapy Zolgensma last year. Bearing a list price tag of $2.125 million, it stands as the world’s most pricey drug.

That celebrated approval was quickly overshadowed by a data manipulation scandal at Novartis’ gene therapy unit AveXis. Although the animal testing data in question were doctored before Novartis took over the AveXis business, the company’s decision to wait—while running what it called a more in-depth investigation—after Zolgensma’s FDA approval to alert the FDA drew wide criticism.

The incident dealt another blow to the Swiss pharma’s reputation after the Michael Cohen payment scandal in 2018. It led to the departure of two top AveXis scientists, prompted CEO Vas Narasimhan to promise faster data integrity disclosures and cost him a proportion of his 2019 bonus. 

RELATED: FDA lets Novartis off the hook in Zolgensma data manipulation

But that didn’t stop Zolgensma from becoming a commercial success, with expectation-busting sales quarter after quarter. In 2019, Zolgensma raked in $361 million, as Novartis celebrates an uptick of newborn screening for the rare disease. Japanese and European drug reviewers recently gave their thumbs-ups. Now, the company is hoping to expand into older patients with a new formulation, though that effort has hit a safety snag.

Besides Mayzent and Zolgensma, Novartis also won approvals for Piqray as the first PI3K inhibitor for a solid tumor, Adakveo for sickle cell disease, and Beovu for wet age-related macular degeneration.

On that last item, just as Novartis was going after Regeneron’s market-leading Eylea on the strength of some wins in a head-to-head trial, the American Society of Retina Specialists sent out an alert about a potential risk of vision loss. A Piper Sandler survey of doctors showed less support for the Novartis drug and a “mistrust” of the company after that alert.

RELATED: 'Lightning struck': How a safety alert shifted doctor sentiment on Novartis' Beovu

Meanwhile, in cardiology, Novartis’ Entresto grew sales by 71% to $1.73 billion, a hefty boost. But the drug narrowly missed its goal of cutting deaths and emergency hospitalizations in a key phase 3 trial of heart failure patients with preserved ejection fraction (HFpEF), an indication that covers a global patient population of 13 million.

The drug did deliver some improvements—though not statistically significant—and provided greater benefits in some subgroups. Novartis said it still intends to file for U.S. approval in HFpEF this year. 

Moving into 2020, Novartis’ cardiovascular department could see a new blockbuster entrant in the form of anti-PCSK9 siRNA therapy inclisiran, the centerpiece of its $9.7 billion buyout of The Medicines Company. While existing PCSK9 antibodies—Amgen’s Repatha and Sanofi and Regeneron’s Praluent—have suffered from slow launches and payer pushback, Novartis hopes inclisiran’s less frequent dosing schedule, paired with its decades-long CV marketing experience with its valsartan franchise, could turn the new LDL-c drug into a success. Some analysts argue the company still faces an uphill fight, though, especially given the hefty price it paid to take in the med.

On the personnel front, Novartis last year bid farewell to its pharma chief Paul Hudson, who now heads up Sanofi. Former Advanced Accelerator Applications president Marie-France Tschudin has filled the place, joining two other women, Novartis Oncology chief Susanne Schaffert and General Counsel Shannon Klinger, on the Swiss drugmaker’s executive committee.

The drugmaker also brought back Richard Saynor from GlaxoSmithKline to be CEO of Sandoz, which is in the process of gaining more autonomy. The generics division appears to be stabilizing, with 2019 sales of $9.73 billion, up 2% at constant currencies. The growth was mainly driven by the European market and injectables.

One of Sandoz' goals for the year was thwarted, though. Aiming for a leaner organization focused on hard-to-copy generics and biosimilars, Sandoz in 2018 agreed to sell some other lines—U.S. oral solids and its dermatology business—to India’s Aurobindo Pharma. Over a year and a half later, after repeatedly putting off a closure date, the pair scrapped the transaction, citing delays at the Federal Trade Commission. Now Sandoz will have to continue dealing with the declining U.S. portfolio.

4. Novartis