Novartis CEO Vas Narasimhan said to CNBC on Tuesday: "This drug could become one of the biggest drugs in our history." The Swiss pharmaceutical company is betting that the peak annual sales of its experimental multiple sclerosis (MS) drug remibrutinib will exceed $4 billion.

A few days ago, Barclays downgraded its forecast for the peak sales of this drug after the publication of detailed results from two subsequent trials. The results showed that the drug's ability to reduce relapses in patients with multiple sclerosis was lower than what analysts had anticipated.

This also highlights the challenges that Novartis faces as it prepares to outline its long-term growth strategy in mid-November.

This week, despite the loss of key patent protection for the blockbuster heart drug Entresto, the pharmaceutical company still reported sales growth. However, Barclays analysts noted that the market has already begun to focus on the next patent cliff, with the best-selling drugs Kisqali and Kesimpta expected to face patent expiration around 2032.

Barclays analysts said on Wednesday that this is "the bigger problem for the market," and pointed out that the maturity of only Kisqali and Kesimpta represents a peak sales volume of $18 billion.

In this context, Novartis indicates that the total sales, including indications other than relapsing-remitting multiple sclerosis for remibrutinib, will exceed $8 billion.

Experts on multiple sclerosis at the University of Pennsylvania, Amit Bar - Or, indicate that remibrutinib seems to have promising safety profiles, but it is unlikely to be as effective in controlling relapsing-remitting multiple sclerosis as Novartis' own highly effective antibody drugs such as Kesimpta.

He added that the greatest opportunity for market expansion for this drug could arise if ongoing trials demonstrate its efficacy against progressive multiple sclerosis, as treatment options in this area are still limited.

Mechanism of Action of remibrutinib

remibrutinib belongs to a class of drugs known as BTK inhibitors, which are designed to reduce the activity of the immune system that can damage the nerves of patients with multiple sclerosis.

The mechanism of action of Kesimpta is different. It is a monoclonal antibody that can bind to the CD20 protein, eliminating B cells involved in the autoimmune response of multiple sclerosis.

Unlike Kesimpta, remibrutinib attempts to regulate the activity of these cells, rather than eliminating them.

Bar-Or Distinguishes the biological differences between relapsing-remitting multiple sclerosis and progressive multiple sclerosis: patients with the former experience recurrent episodes, while those with the latter will gradually deteriorate over time.

Bar-Or indicates that the clinical outcomes of remibrutinib in relapsing-remitting multiple sclerosis seem to be similar to those of Roche's competitor, BTK, which is an inhibitor of fenebrutinib. However, in terms of preventing relapses, it is not as effective as anti-CD20 therapies such as Kesimpta.

Currently, there are no head-to-head trials that directly compare remibrutinib with fenebrutinib or therapies that target CD20, making it difficult to conduct a direct comparison.

He added that for patients who are undergoing treatment for CD20 but whose condition is progressing, this drug may still be an attractive option for conversion. A clinical trial investigating whether remibrutinib can effectively treat progressive multiple sclerosis is expected to release its results in 2031.

BTK One potential advantage of inhibitors is that they modulate immune cells rather than eliminating them, which may make their long-term safety profile superior to some current treatments for multiple sclerosis, Bar-Or says. However, he adds that there is still a lack of sufficient long-term safety data to confirm this.

A Novartis spokesperson stated to CNBC that the company primarily views remibrutinib as an opportunity to expand its multiple sclerosis product portfolio, rather than a replacement for the sales of Kesimpta.

The company is targeting patients who have recently been diagnosed, those currently using oral therapies, as well as patients who may meet the criteria for conversion and are undergoing treatment with anti-CD20 therapies.

Novartis believes that the peak annual sales of Kesimpta for relapsing-remitting multiple sclerosis are expected to exceed $6 billion, while those of remibrutinib are also expected to exceed $4 billion.

Sales Prospects of remibrutinib

Chenxing Analyst Jay Lee told CNBC that Novartis' peak sales forecast of "over $4 billion" for remibrutinib in the field of multiple sclerosis is "within the possible range," but it has not yet been "de-risked."

Lee added that this will depend on the comparison results of remibrutinib with Roche's competing drug fenebrutinib, the situation of price negotiations, whether its potential tolerance advantages can be translated into patients' ability to adhere to treatment for a longer period, and whether clinical trials support the switch from current multiple sclerosis therapies.

In the short term, I expect that the largest market for remibrutinib will be the oral conversion market, which refers to patients who are currently using counterfeit oral medications and need to switch to alternative treatments, especially due to tolerance issues.

Currently, investors are focusing on the RESHAPE trial. This trial involves patients aged 40 to 70 who are using Roche's anti-CD20 antibody Ocrevus. Results are expected to be announced in 2028.

Lee indicates that although this may allow remibrutinib to seize some market share from Ocrevus, Kesimpta, and other CD20 drugs, "if this means that Novartis can gain a larger share of patients with relapsing-remitting multiple sclerosis from the market currently led by Roche, then that could still be beneficial for Novartis," it is added. Novartis estimates that among patients who meet the conversion criteria and are currently using CD20, about 75% are not using Kesimpta.

In addition, remibrutinib has been approved for the treatment of certain types of chronic urticaria, and the results of a late-stage clinical trial for chronic inflammatory skin disease hidradenitis suppurativa ( HS ) are expected to be announced before November 19th.

Barclays estimates that the peak annual sales opportunity for HS in its indicated indications could reach $2 billion, but due to an unusual dose-response pattern observed in mid-stage trials, as well as a history of late-stage trial failures in the HS domain, the bank assigns only a 50% probability of success to this drug.