Multiple sclerosis has become an increasingly competitive and crowded market for big drug companies- putting them in a vulnerable position to pricing pressures. And currently, GILENYA, Novartis (SIX: NOVN, NYSE: NVS) is leading the way with Celgene (NASDAQ: CELG) Ozanimod recently passed the Phase III “SUNBEAM” trial to put itself for the launch by end of this year. Henceforth, we look at how GILENYA stands once Ozanimod enters this market.
GILENYA Background:
Gilenya (Fingolimod) is a S1P receptor modulator, which is indicated for treatment of relapsing-remitting multiple sclerosis in patients, whose disease has failed to respond to beta-interferon or is severe and getting worse rapidly. The drug is used to reduce the frequency of clinical exacerbation as well as to delay the accumulation of physical disability.
Safety concerns:
According to the various specialists, Gilenya has tolerability issues; most notably a slowing heart rate (bradycardia or bradyarrhythmia) which forces doctors to monitor patients after the first dose is taken. Adding to that, the risk of serious heart rate effects increases when Gilenya is taken with certain drugs (Methadone, Citalopram, Ketaconazole) or when patient has low potassium/magnesium. Subsequently, it is certain that taking more than the 0.56mg dose won’t trigger any further benefits/improvement, but will only cause more side effects. Moreover, according to the researchers in Japan, it can remain in your blood for up to 2 months after completion of the course- this is risky for the immune system as it will not be as responsive as it should be during the standard drug withdrawal period. Gilenya can also trigger the risk of serious infections and diminish the way vaccines work in our body as to prevent certain diseases, notably, the chicken pox vaccine. It can lower the number of white blood cells (lymphocytes) in the body before it goes back to the standard levels within 2 months of stopping the treatment. Lastly, Gilenya have chances of causing Progressive multifocal leukoencephalopathy (PML), which is a rare brain infection that usually leads to death or severe disability. PML usually happens in people with weakened immune systems.
Drug Verdict:
Gilenya is an oral medication that has a lot of side effects, but it reduces the number of flare-ups, slows physical changes, and decreases the number of new brain lesions in relapsing MS.
Ozanimod Background:
Ozanimod is a selective S1P receptor modulator. It is developed to act by retaining certain white blood cells in the body’s lymph nodes, preventing them from entering the central nervous system by keeping them out of circulation.
Upsides from successful trails:
Ozanimod was found to reduce the frequency of MS relapse in SUNBEAM (phase III trial), and meeting its primary endpoint in reducing ARR, while keeping the overall safety and tolerability profile stable with the previous phase II trials. And in contrast to GILENYA, Ozanimod was well tolerated with no cardiac effects were observed and liver toxicity was minimal. With Celgene conducting a second phase III study of ozanimod in MS patients (results expected in Q2). From the investor’s perspective, Celgene’s Ozanimod puts the project on track for approval in MS, which gives some justification to the $7.2B paid to acquire Ozanimod’s originator, Receptos.
Safety Confirmation pending:
Despite shining in the Phase III trial, safety data still thin on the ground, as it is unclear whether ozanimod will get a favourable label than rival S1P modulator Gilenya (Novartis). According to Mark Schoenebaum, Evercore ISI analyst, there was a single incidence of bradycardia in a patient (phase II RADIANCE MS data) with a history of issue and patients average overall reducation in heart rate was less than 2bpm compare to 8.1bpm for Gilenya.
Henceforth, Celgene will need to confirm detailed safety data from both SUNBEAM and phase III portion of RADIANCE as to prove that there is a safety competitive advantage over Gilenya, if ozanimod is to hit the peak $4-6B in sales in the MS + ulcerative colitis combined, which was projected by CELG at time of Receptos purchase.
Another advantage would be when studies confirms that ozanimod does not require first-dose monitoring, allowing CELG to grab shares from Gilenya- ultimately challenging Gilenya generics, which could be in the market by 2019 latest.
Celgene in the S1P modulator market:
Once ozanimod get approved within the projected time-frame, it will have a head start on several other S1P selective modulators. Such as Ponesimod from J&J is due to report data from the Optimum phase II trial in RMS by 2019, while Novartis’s siponimod is in phase III trial in another form of MS- with completion date of December 2020.
| Project | Company | Mechanism | Status | 2020e sales ($m) |
| Gilenya | Novartis | Pan S1P modulator | Marketed | 1,375 |
| Ozanimod | Celgene | S1P 1 & 5 modulator | Phase III | 2,127 |
| Siponimod/ BAF 312 | Novartis | S1P 1 & 5 modulator | Phase III | 865 |
| Ponesimod | Actelion/J&J | S1P agonist | Phase III | 88 |
| Amiselimod/MT-1303 | Mitsubishi Tanabe | S1P 1 antagonist | Phase II | 1 |
Source: EvaluatePharma.
Therefore, for now things are looking to outperform as expected by the street and investors will hope that further positive results in MS could push towards achieving its 2020 sales guidance of $21B.
Bruce Cree, Associate Professor of Neurology, Multiple Sclerosis Center, University of California stated that safety and efficacy results from SUNBEAM are consistent with the long-term results from the phase II trial (RADIANCE). The data add to the growing body of evidence supporting the use of Ozanimod as disease modifying therapy for relapsing forms of multiple sclerosis.
To me, this drug looks like the safest in the class,” Dr Jeffrey A. Cohen, MD, Director, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, OH
Resources:
http://www.ms-uk.org/celegen%E2%80%99s-ozanimod-successful-reducing-relapse-rates-020317
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