3. Novartis

Novartis
Novartis' regulatory timeline for cholesterol drug inclisiran and an intrathecal formulation of gene therapy Zolgensma didn't work out as planned. (Novartis)

Novartis
2020 revenue: $48.66 billion
2019 revenue: $47.45 billion
Headquarters: Basel, Switzerland

Novartis officially folded in The Medicines Company at the beginning of 2020. The next step would securing an FDA go-ahead for the $9.7 billion acquisition’s centerpiece—PCSK9 cholesterol drug inclisiran—to get the blockbuster ball rolling. But COVID-19 derailed that plan.

When the original decision date came in December, the FDA issued a complete response letter, not because of efficacy, or safety, but unresolved “inspection-related conditions” at a facility in Italy where a contractor helps manufacture the drug. The agency wasn’t able to inspect the plant due to COVID-19, and it wasn’t satisfied with the paperwork Novartis provided instead.

RELATED: The 10 most-anticipated drug launches of 20216. inclisiran

The drug did get an EU green light under the brand Leqvio in December, but its U.S. timeline remains unclear. Novartis CEO Vas Narasimhan said Novartis would respond to FDA's requests by Q3 of this year. But if the agency insists on an on-site check-up—and with foreign travel restrictions still in place, the approval could remain stalled. Meanwhile, Novartis is working on a tech transfer to its own facility.

Leqvio wasn’t the only regulatory setback Novartis suffered last year. The Swiss pharma was aiming for a 2021 filing for a new formulation of gene therapy Zolgensma that’s infused into the spinal fluid rather than intravenously. If approved, it would allow the drug to reach spinal muscular atrophy patients up to 5 years of age.

However, the FDA said it wants a separate pivotal phase 3 trial on top of an existing phase 1/2 study to consider Novartis’ application. The new requirement effectively pushed a filing to at least 2023, industry watchers figured.

RELATED: Novartis Gene Therapies president talks Zolgensma competition, path forward for new formulation

And while Zolgensma’s intrathecal formulation hit a snag, Roche was able to launch a new oral option, Evrysdi, for SMA patients 2 months and older. But SVB Leerink analyst Mani Foroohar predicted Evrysdi would mainly steal share from Biogen’s Spinraza in older patients. 

Thanks to an EU approval and Japan’s reimbursement decision in May, Zolgensma raked in sales of $920 million in 2020, up about 150% year over year despite the pandemic.

Those road bumps aside, Novartis chalked up several wins in 2020. It turned the cancer drug ofatumumab into an FDA-approved multiple sclerosis therapy now sold under the brand Kesimpta. It’s viewed as a fierce in-class rival to Roche’s fast-growing Ocrevus.

RELATED: Novartis gets a green light to challenge Roche, Sanofi with delayed MS med Kesimpta

So far, Kesimpta is suffering from a slow launch just as Ocrevus’ growth slows down. Doctors have been hesitant to switch therapies and worry that the two drugs’ mechanism of targeting B cells could reduce protection against COVID or response to vaccinations, the company said. 

Novartis pharma chief Marie-France Tschudin said the company is running some related tests to help patients and physicians feel more comfortable using the med amid the pandemic.

Besides Kesimpta, Novartis won U.S. clearance for Tabrecta in non-small cell lung cancer with MET exon 14 skipping mutations, which make up about 3% to 4% of newly diagnosed NSCLC cases. The May approval came nine months ahead of Merck KGaA’s rival Tepmetko in the same indication.

RELATED: Novartis 'not leaving any stone unturned' for Kesimpta, Leqvio as Entresto, Cosentyx drive growth

Cosentyx, currently Novartis’ top-selling drug with $4.0 billion in 2020 sales, added non-radiographic axial spondyloarthritis to its label, matching up to Eli Lilly’s IL-17 rival Taltz.

Heart med Entresto—another key growth engine at the Swiss pharma—recently snagged an FDA go-ahead to expand into heart failure with preserved ejection fraction (HFpEF). It’s a significant win, given how the drug narrowly missed its primary goal in that patient group in a phase 3 trial. About 2 million of HFpEF patients in the U.S. have an ejection fraction below normal, according to Novartis’ estimates.

The drug delivered a 44% year-over-year sales growth, to $2.50 billion in 2020. With the new indication, Novartis’ dialing up peak Entresto sales by $1 billion to around $4 billion to $5 billion.

3. Novartis