Novartis AG (ADR) (NYSE:NVS) just put out data from its multiple sclerosis (MS) trial, and it looks as if the company is winning the race to bring a drug to market that offers a solution for patients with secondary progressive MS (SPMS), a severe form of the condition. Biogen Inc (NASDAQ:BIIB) is also working on a compound, but the drug failed to meet its primary endpoint on a pivotal last year. We don’t yet know when Novartis is set to submit to the FDA, but the company is usually pretty quick on its NDA turnarounds, and so ahead of the submission, here’s a look at the drug in question and what we know so far about the chances of approval.
The drug is called siponimod, and as mentioned, it’s targeting SPMS. To understand its MOA, it’s first important to understand MS. The condition is associated with three primary characteristics – demyelination, inflammation and blood brain barrier permeation. The first is the stripping (or degrading) of the myelin sheath – the coating that protects nerve cells. The second is the T Cell response to myelin, and the inflammation that follows. The third is the entry of these T Cells into the CNS. It’s the second and the third one one that we’re interested in here. The drug is what’s called a selective sphingosine-1-phosphate receptor modulator. T cells are a type of lymphocyte, and lymphocytes express the aforementioned receptor. Siponimod binds to the receptor, and this binding stops the T cells from crossing the blood brain barrier. No crossing means no inflammatory response to myelin degradation.
Secondary progressive MS is defined as MS that occurs after another type of the condition called relapsing remitting MS. It’s really just a technical term for a return of the condition, and it’s often difficult to distinguish between the two types. However, patients who are diagnosed with SPMS have a pretty poor prognosis. The symptoms associated with generic MS get steadily worse, and the current SOCs in the space, the disease modifying drugs, don’t work in many cases (and have very limited efficacy in the other cases).
The MOA is very similar to an already approved Novartis drug, Gilenya, but its overcomes one of the side effects associated with the latter – lymphocytopenia. Lymphocytopenia occurs as a result of the T cell sequestering, and is the abnormally low level of lymphocytes in the blood.
So what do we know about the data?
Well, Novartis was working towards a primary endpoint of cutting the risk of three-month disability progression versus placebo. The company has been pretty vague in its publishing a discussion of exactly how things turned out, but we know that in a randomized, double-blinded, placebo-controlled study, across more than 1,600 patients, the study hit its primary endpoint. It also hit on a variety of secondaries, and the safety profile looks clean.
What does the data mean for Novartis?
This data is the latest in a string of efforts to maintain MS dominance. Novartis’ blockbuster MS drug, the above mentioned Gilenya, generates more than $2 billion annually for the company, however it is set to face off against generic competition when its patent expires come 2019. This initial indication, SPMS, is a pretty small market, but there’s every chance Novartis will look to expand its indication beyond the initial target if the FDA gives the company a green light for approval. As such, siponimod has the potential to be a blockbuster farther down the line, if every thing runs smoothly.
From a timeframes perspective, as we’ve said above the company hasn’t put out a specific target date fro an NDA submission. However, we can take a stab at a target data an assume that Novartis will present the data at the keystone MS conference in London next month, and then look to submit to the agency by the end of the fourth quarter. This gives us a potential approval before the end of 2017.
All said, this one is more about maintaining a revenues stream from the MS space than it is developing a new source. The patent protection currently in place stopping generic competition, as mentioned, is out at the end of the decade, an an approval for siponimod will help secure some of the potentially lost revenues.