How big is the DMT pie? Is there space for ‘Me Toos’? #ResearchSpeak #MSBlog #MSResearch
“As the MS DMT market matures the appearance of ‘Me Too’ drugs will increase. The phase 2 study below is of a new S1P modulator called Amiselimod. This is one of many ‘Me Too’ S1P-modulators in development hoping to get to market and carve out a slice of the $20-billion+ MS market and/or to extend into other disease areas. Some of the other S1P-modulators in development are Siponimod (Novartis), Ozanimod (Celgene), Ponesimod (Actelion), Ceralifimod (Ono), MT-1303 (Biogen-Mitsubishi), etc. An important issue in the MS space is that fingolimod is due to come off-patent soon and there is little doubt the price of fingolimod will come down substantially. I would predict that generic fingolimod will be over 70% cheaper than the innovator formulation (Gilenya). Generic fingolimod will have a major impact on the market, which is becoming increasingly price sensitive. Depending how generic fingolimod is used it may reduce the size of the DMT market by 40%; this means the ‘Mee Toos’ will left fighting over the crumbs.”
“The one issue we have in Europe is that fingolimod is essentially a 2nd-line drug and it only recently had its label changed to treat rapidly-evolving severe (RES) MS as a first-line option. With natalizumab licensed for RES, and ocrelizumab due to be licensed, I doubt fingolimod will be used much as a 1st-line agent for patients with RES-MS. I also doubt Novartis has any incentive to get fingolimod a 1st-line label in Europe now that they have ofatumumab (anti-CD20) in development. So it will be left to us, the MS community, to explore ways to get the label of fingolimod changed in Europe.”
“Of the other S1P modulators in development Spinonimod is the closest to market; the phase 3 results of the large SPMS trial is due to report. Please note that Siponimod is being developed for SPMS, and not RRMS, therefore Siponimod is hoping to expand the pie. This would be very good news for SPMSers. The others S1P modulators may have a space if the can improve on fingolimod’s safety profile, i.e. fewer cardiac side effects, and are able to deliver more efficacy than fingolimod. Based on their pharmacokinetic & pharmacodynamic profiles and early phase 2 results some of these agents promise to do just this. However, the main problem of S1P-modulators going forward will be long-term immunosuppression, with opportunistic infections and secondary malignancies, being the main concern.”
“Personally, I remain optimistic that a Black Swan will deliver a cure, or MS prevention, then the pie will become very small with even fewer crumbs.”
|How big is the MS pie?
Kappos et al. Safety and efficacy of amiselimod in relapsing multiple sclerosis (MOMENTUM): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurology 2016 (Epub).
Background: Patients with multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system with autoimmune pathogenesis, have shown partial response to a number of immunomodulating treatments, but the search for more effective, safe, and convenient therapeutic options continues. Amiselimod is an oral selective modulator of sphingosine 1-phosphate 1 (S1P1) receptor, which is being developed for the treatment of various autoimmune-mediated diseases. We assessed the safety and efficacy of amiselimod in patients with relapsing– remitting multiple sclerosis.
Methods: In this double-blind phase 2 trial, patients aged 18–60 years with active relapsing–remitting multiple sclerosis from 84 centres in Europe and Canada were randomly assigned (1:1:1:1) with an interactive web-response system to receive once daily oral amiselimod 0·1 mg, 0·2 mg, 0·4 mg, or placebo for 24 weeks. All study personnel, site personnel, investigators, and patients were masked to the treatment assignment during the study. The primary endpoint was the total number of gadolinium-enhanced T1-weighted lesions on monthly brain MRI scans from weeks 8 to 24. Analysis was done on the predefined evaluable population (all randomised patients who did not have any major protocol deviations, completed 24 weeks of treatment as planned, and had at least three valid post-dose MRI scans). This trial is registered with ClinicalTrials.gov, number NCT01742052.
Findings: Between Jan 31, 2013, and Dec 24, 2013, 536 patients were screened and 415 patients randomly assigned to amiselimod 0·1 mg (n=105), 0·2 mg (n=103), 0·4 mg (n=104), or placebo (n=103). The median total number of gadolinium-enhanced T1-weighted lesions from weeks 8 to 24 did not differ between the amiselimod 0·1 mg and placebo groups (median 1·6 lesions [range 0–132] in the placebo group vs 2·0 [0–105] in the 0·1 mg group [median difference 0·0, 95% CI −1·0 to 0·0, p=0·7517]), but was significantly lower in the two higher amiselimod dose groups than in the placebo group (0·0 lesions [range 0–35] in the 0·2 mg group [median difference vs placebo −1·0, 95% CI −1·0 to 0·0, p=0·0021] and 0·0 [range 0–30] in the 0·4 mg group [–1·0, −1·2 to 0·0, p=0·0003]). The estimated incident rate ratio compared with placebo was dose-dependently decreased with amiselimod (0·1 mg 0·53 [95% CI 0·33–0·85; p=0·0079], 0·2 mg 0·39 [95% CI 0·24–0·63; p=0·0001], and 0·4 mg 0·23 [95% CI 0·14–0·38; p<0·0001]). The incidence of treatment-emergent adverse events, including infections and cardiac disorders, were similar in the amiselimod treatment groups (59 [56%] of 105 patients in the 0·1 mg group, 69 [67%] of 103 in the 0·2 mg group, and 58 [56%] of 104 in the 0·4 mg group) to the incidence in the placebo group (66 [64%] of 103 patients); the most common treatment-emergent adverse events were headache (ten [10%], ten [10%], and ten [10%] vs four [4%]) and nasopharyngitis (nine [9%], seven [7%], ten [10%] vs eight [8%]). No serious treatment-emergent adverse event was reported for more than one patient in any group and no clinically significant heart rate reduction was observed at any amiselimod dose.
Interpretation: Amiselimod 0·2 mg and 0·4 mg significantly reduced the total number of gadolinium-enhanced T1-weighted lesions. The safety and efficacy profiles of amiselimod suggest that this S1P1 receptor modulator is a new potential treatment in multiple sclerosis and potentially other immune-mediated inflammatory diseases and deserves further investigation.
Funding: Mitsubishi Tanabe Pharma Corporation.