Novartis AG is developing a trio of medicines that draw on the Swiss drugmaker's expertise in cardiovascular, neurological and genetic disorders to replace billions of dollars set to be lost to patent expiries on some of its best-selling therapies.

A new version of its $2.1 million one-time gene therapy Zolgensma, multiple sclerosis drug remibrutinib and cardiovascular drug pelacarsen are three of the most exciting experimental therapies out of a pipeline of 54 in phase 3 trials, Marie-France Tschudin, president of Novartis' pharmaceuticals division, told S&P Global Market Intelligence.

The Basel, Switzerland-based company has expanded its research and development capabilities to encompass innovative technologies like cell and gene therapies such as Kymriah, the first-ever U.S.-approved chimeric antigen receptor T cell, or CAR-T, therapy. These pioneering approaches will be used as a springboard for further expansion into lucrative markets beyond Europe as the company prepares to face generic competition in the next five years.

"We're focused on U.S. and China," Tschudin said. "Those are really big growth opportunities for us."

Patent cliff ahead

By 2027, Novartis is likely to lose $14 billion of sales from expiring patents on multiple sclerosis medicine Gilenya, eye medicine Lucentis and heart medicine Entresto — which pulled in $3.5 billion of sales in 2021 — among others, according to Jefferies.

The company intends to combat this erosion with a raft of new drug launches spanning immune system disorders like Sjögren's syndrome, lupus and hives, as well as food allergies, Parkinson's disease and cancer. Jefferies, which rates Novartis a "buy," forecast that sales from these new therapies — the majority of which will be filed for approval after 2025 — will equate to the patent-induced losses.

"Novartis must circumnavigate the expiry of a number of patents in its branded pharma business over the next few years," Berenberg analyst Kerry Holford said in a Jan. 28 note. "However, growth from its recently launched drugs and its large late-stage pipeline can more than fill the gap."

A key target for Novartis is heart disease, which remains the leading cause of death worldwide. The disease kills 18 million people a year, even with the adoption of healthier lifestyles, advances in treatments and the success of cholesterol-cutting medicines like statins introduced in the 1980s, according to the World Health Organization.

"If there's one place to start, it's in cardiovascular disease," Tschudin said. "It's top of mind for every single healthcare system worldwide. It's a massive cost burden to society and when you think of it, 80% of it is preventable."

Embarking on a new approach to lowering cholesterol that uses RNA interference, or RNAi, to boost the liver's ability to remove the harmful lipid from the blood, Novartis launched a twice-yearly injection called Leqvio in 2021. Now approved in 50 countries, including in the U.S. in December 2021, this preventative approach tackles both the genetic factors for high cholesterol and low adherence among patients with heart disease, more than half of whom stop taking their statins within two years in the U.S., Tschudin said.

Leqvio received U.K. approval in September 2021 and has been introduced as a first-of-its-kind pilot scheme within the National Health Service, treating 300,000 people with high cholesterol after Novartis agreed to a commercial deal with the state-run health body NICE. Details of the deal were not disclosed.

"COVID has shown us that there is an opportunity to collaborate much more proactively with [healthcare] systems and have the systems work with us," Tschudin said. "Right from the get-go, I work with the objectives that are important, with an affordability that makes sense for [that] country, so that we can actually deliver this drug to many more patients than otherwise would have access to it."

Novartis plans to apply this more collaborative method to the rollout of pelacarsen, should it be approved after 2025. The drug targets an inherited cardiovascular condition that cannot be treated with diet or exercise and for which no other medicine exists.

"This is something that has the opportunity to piggyback on some of the work that we're doing [with Leqvio] in terms of really working with systems ... and then going forward with much more robust preventative cardiovascular health," Tschudin said. "We're very excited about that."

Still, with the gulf in pricing between the U.K. and the U.S., unlocking the American market is key if Leqvio is to come close to reaching CEO Vas Narasimhan's ambition of becoming Novartis' best-selling drug with annual sales of over $6 billion.

"This is a multiyear journey," Narasimhan said on a Feb. 2 earnings call. "This year will be about building foundations and we hope in 2023 to start to see more appreciable sales from the asset."

The different pricing environments in the EU and the U.S. have had knock-on consequences for access to medicines in European countries, Tschudin said.

"With all of the challenges that they have on pricing, the reality is that the U.S. has been relatively open in terms of allowing access to innovation early," Tschudin said. "We need to start to bend the curve in a different direction, where we start to open up access much more [in Europe]. That is ... what we're trying to do with Leqvio."

Opportunities in China

Novartis also has its eye on China, with psoriasis medicine Cosentyx — which posted global 2021 sales of $4.7 billion — earmarked for particularly strong growth in the region. Biologic drugs have yet to penetrate the market in a major way, with about 6 million underserved psoriasis patients in China, Tschudin said.

This strategy moved a step closer with Cosentyx's inclusion on China's National Reimbursement Drug List last year, allowing the therapy to be added to hospital formularies. While significant copays for patients mean there are still affordability issues, that has not stopped Novartis from being extremely ambitious about the medicine's potential for growth in the country, Tschudin said.

The drugmaker is also investing in a future rollout of Leqvio and therapies for conditions such as multiple sclerosis, which Tschudin said is considered a rare disease in China.

"We're thinking very bullishly about China in general," the executive said.

In the next decade, Novartis plans to dive deeper into areas of research where it has already invested, like neurology. With 11 experimental medicines in the therapeutic area as of Feb. 2, Tschudin highlighted remibrutinib, which is in phase 3 trials for multiple sclerosis, as another top pipeline pick.

"In the next 10 years, we have to make progress in some of these diseases and that goes for anything from Parkinson's to Alzheimer's to mental health," Tschudin said. "All of these areas are going to become extremely important so it would be remiss of us to not have an eye on that."