Novartis' Zolgensma, Leqvio lag among new launches as Entresto and Pluvicto steam ahead

As Novartis prepares to spin off Sandoz to become a pure-play innovative medicines company, several of the Swiss pharma’s new medicines have started taking diverging launch trajectories. 

Spinal muscular atrophy gene therapy Zolgensma and closely watched cholesterol fighter Leqvio disappointed in the fourth quarter, delivering sales below analyst expectations. On the flip side, heart drug Entresto, radiotherapy Pluvicto and multiple sclerosis treatment Kesimpta delivered growth that came ahead of Wall Street estimates.

After a surprise decline in the third quarter, Zolgensma sales again dropped 3% sequentially to $309 million, which came 12% below consensus estimates, according to Jefferies analysts. Full year sales of the gene therapy reached $1.37 billion, a 5% increase from 2021 at constant currencies.

As he did after the third quarter, Novartis CEO Vas Narasimhan again attributed the lackluster performance to a shift from the initial uptake in existing patients to newborn screening at this phase in the launch.

“Growth now is largely dependent on adding additional countries in emerging markets around the world,” Narasimhan told investors during a call Wednesday. The CEO said Zolgensma sales will stabilize in the $1.5 billion range until the drug can reach older patients with an intrathecal formulation in 2025 or beyond.

Meanwhile, another drug on investors’ minds is Leqvio. The PCSK9 RNA interference therapy chalked up $42 million sales in the fourth quarter, missing analyst estimates by 14%.

Novartis has repeatedly said Leqvio’s sales ramp will be slow because of a buy-and-bill reimbursement requirement which is new for cardiologists. The company made some progress on the launch in the fourth quarter, having increased the number of doctors who have prescribed the drug by 50% over the prior quarter to 7,200, Narasimhan said.

Looking at Leqvio’s monthly sales, Narasimhan noted that it’s actually slightly ahead of the launch trajectory of the company’s star cardiovascular product Entresto, which had initially also suffered a long period of slow adoption.

Speaking of Entresto, the heart failure combo med beat consensus estimates by 8% with $1.29 billion in fourth-quarter revenues. That marked 44% growth year over year at unchanged exchange rates. With $4.6 billion in full-year sales, Entresto now makes up 11% of Novartis’ total innovative medicines haul, which grew 4% at constant currencies to $41.3 billion.

In addition, prostate cancer drug Pluvicto ginned up $179 million sales during the quarter—its third on the market. The performance came 72% ahead of analyst projections.

Novartis is hitting a delay in its Pluvicto expansion efforts, though.

Novartis in December announced that the phase 3 PSMAfore trial testing Pluvicto in that setting met its primary endpoint of progression-free survival. But the FDA wants to see more mature overall survival analysis, which Novartis expects to have in the middle of the year for a filing in the second half of 2023, Narasimhan said.  

Meanwhile, another Novartis oncology asset is on a more protracted delay. An application for BeiGene-partnered PD-1 inhibitor tislelizumab has long passed the FDA’s target decision date as the agency couldn’t conduct pre-approval inspections in China.

China in late 2022 relaxed its strict zero-COVID policy. But during a separate call with reporters on Wednesday, Narasimhan said Novartis still doesn’t have any update on the timing of inspection, indicating that the FDA has yet to even schedule the check-up.

As for more established medicines, the company's top-selling drug Cosentyx generated $1.1 billion in the fourth quarter, a 9% decline at constant currencies, after years of steady growth. 

A big part of the Cosentyx drop came from a revenue deduction from prior quarters as a result of higher-than-expected utilization by Medicaid and hence a higher rebate, Narasimhan explained. But even after removing that factor, Cosentyx’s U.S. revenue in the fourth quarter dropped by 6%.

Narasimhan warned investors that the decline might continue for a couple more quarters, but he stood by the company’s $7 billion-plus peak sales projection for the inflammatory disease drug. The growth will come from expansions in the EU and China, as well as new indications, he said.