A pharma giant is moving past one patent cliff — but another is already looming - CNBC

"This medicine could be one of our largest medicines in history," Novartis CEO Vas Narasimhan told CNBC on Tuesday, as the Swiss drugmaker backed remibrutinib, its experimental MS medicine, to generate more than $4 billion in peak annual sales.

Days before, Barclays cut its forecast for the drug's peak sales after detailed results from two late-stage trials showed the drug had reduced relapses in MS patients by less than analysts expected.

It highlights a challenge for Novartis as it prepares to outline its long-term growth strategy in mid-November.

The drugmaker reported sales growth this week despite losing key patent protection for blockbuster heart drug Entresto. But Barclays analysts said that the market is already looking to the next patent cliff, with bestsellers Kisqali and Kesimpta facing patent expirations around 2032.

That's "the market's bigger question," Barclays analysts said on Wednesday, noting Kisqali and Kesimpta expiries alone represent $18 billion in peak sales.

Against that backdrop, Novartis has guided for $8 billion-plus in total sales of remibrutinib, including indications other than relapsing MS.

Amit Bar-Or, a multiple sclerosis specialist at the University of Pennsylvania, told CNBC that remibrutinib appeared to offer a promising safety profile but was unlikely to control relapsing MS as effectively as high-efficacy antibodies like Novartis' own Kesimpta.

He added that the drug's biggest opportunity to expand the market could emerge if ongoing trials demonstrate a benefit in progressive multiple sclerosis, where treatment options remain limited.

Remibrutinib belongs to a class of medicines known as BTK inhibitors, which aim to reduce the immune system activity that damages nerves in MS patients.

Kesimpta works differently. It is a monoclonal antibody that binds to the CD20 protein, depleting B cells involved in the autoimmune response in MS.

Unlike Kesimpta, remibrutinib aims to regulate the cells' activity without eliminating them.

Bar-Or distinguished the biology of relapsing MS — in which patients experience flare-ups — from progressive MS, which worsens gradually over time.

Clinical results for remibrutinib in relapsing MS appear to be similar to Roche's rival BTK inhibitor fenebrutinib, but less effective at preventing relapses than anti-CD20 treatments such as Kesimpta, according to Bar-Or.

No head-to-head trials have yet compared remibrutinib with fenebrutinib or anti-CD20 treatments, making direct comparisons difficult.

It could still be an attractive switch for patients who are experiencing progressive MS while on an anti-CD20, he added. An ongoing clinical trial testing whether remibrutinib can effectively treat progressive MS is expected to read out in 2031.

One potential advantage of BTK inhibitors is that they regulate immune cells rather than eliminate them, which could make them safer over the long term than some existing MS treatments, Bar-Or said. However, there is not yet enough long-term safety data to confirm this, he added.

A Novartis spokesperson told CNBC that it views remibrutinib primarily as an opportunity to expand its MS portfolio, rather than replace sales of Kesimpta.

The company is targeting newly diagnosed patients, those currently taking oral treatments, and patients receiving anti-CD20 therapies who may be eligible to switch.

Novartis sees a $6 billion-plus peak annual sales opportunity for Kesimpta alongside $4 billion-plus for remibrutinib in relapsing MS.

Morningstar analyst Jay Lee told CNBC that Novartis' $4 billion-plus peak sales forecast for remibrutinib in MS was "within the realm of possibility" but wasn't "de-risked."

Lee added that this would depend on how remibrutinib compares with Roche's rival fenebrutinib, drug pricing negotiations, whether its potential tolerability advantages translate into patients staying on treatment longer, and whether clinical trials support switching patients from existing MS treatments.

"In the near term, I expect the largest market for remibrutinib will be the oral switch market, i.e. patients taking a generic oral treatment who need to switch, particularly due to tolerability reasons."

For now, investors are focusing on the RESHAPE trial, which enrolled patients aged 40 to 70 taking Roche's anti-CD20 antibody Ocrevus, and is expected to read out in 2028.

While that could allow remibrutinib to take some market share from CD20 drugs like Ocrevus and Kesimpta, it "may still work in Novartis' favor if it means they gain overall RMS patient share from Roche, which currently leads the market," Lee said, adding that Novartis estimates about 75% of switch-eligible patients on CD20 drugs are not on Kesimpta.

Additionally, remibrutinib is already approved to treat certain forms of chronic hives, and a late-stage clinical trial testing it for the chronic inflammatory skin disease hidradenitis suppurativa (HS) is expected to read out before Nov. 19.

Barclays estimates a $2 billion peak annual sales opportunity in HS but assigns the drug only a 50% probability of success, citing an unusual dose-response pattern in mid-stage trials and a history of late-stage trial failures in HS.