Epub ahead of print: Kappos et al. Effect of BG-12 on contrast-enhancing lesions in patients with relapsing-remitting multiple sclerosis: subgroup analyses from the phase 2b study. Mult Scler. 2011 Aug 30.
Background: In the phase 2 study BG-12 240 mg three times daily significantly reduced the number of new Gd-enhancing lesions by 69% compared with placebo.
Objective: In this analysis, the effect of BG-12 240 mg three times daily was evaluated in subgroups based on baseline disease characteristics.
Methods: 257 Ms’ers randomised equally to receive BG-12 (120 mg once daily or three times daily or 240 mg three times daily) or placebo.
Results: BG-12 240 mg three times daily significantly reduced the number of new Gd+ lesions compared with placebo in the following subgroups: EDSS score ≤ 2.5 (74%), EDSS score > 2.5 (63%), no Gd+ lesions at baseline (80%), ≥ 1 Gd+ lesion at baseline (55%), age < 40 years (49%), age ≥ 40 years (89%), female patients (81%), disease duration ≤ 6 years (81%) and disease duration > 6 years (54%); all comparisons were significant
Conclusion: BG-12 decreased new Gd+ lesion development across a range of subgroups defined by baseline disease characteristics or demographics.
“A subgroup analysis like this is often referred to as data mining. However, buried deep in this type of analysis is often important clues regarding the mechanisms of action of drugs and information on who is likely to respond and not respond to the drug. For example, the MS’ers with no Gd+ lesions at baseline seemed to respond more (80% reduction) compared to those with Gd+ lesions (55%). The presence of Gd+ means active disease and this finding with BG12 is contrary to what you find with other drugs that target inflammation. This finding supports the basic science data that BG12 is working in a different way to other ‘anti-inflammatory’ drugs.”
” BG12 is a very interesting drug and is very likely to be neuroprotective; possibly the the ideal add-on drug?”
“As with all science this data will need to be reproduced.”
“For those of you who are interested BG12 works via a factor called NRF2 that is responsible for stimulating a set of cellular programs that protect cells against stress; some people refer to it as the programmed cell survival pathway.”
CoI: Multiple
Extra reading: NRF2
Other posts of interest:
25 Apr 2011
Twice-daily BG-12 significantly reduced the proportion of patients who relapsed at two years by 49% vs. placebo (p<0.0001). On secondary endpoints, BG-12 significantly reduced annualized relapse rate (ARR) and disability …
23 Apr 2011
“In view of the positive phase 3 results and the mode of action of BG12 these results are very exciting. … COI: I sit on the steering committee for the BG12 phase 3 programme and receive consultancy fees for this role. …
18 Apr 2011
The Phase 3 results of another oral agent BG-12 (dimethyl fumarate) in RRMS were reported last week. The top-line results show that 240 mg of BG-12, administered either twice or 3 times daily, met the primary study endpoint …
30 May 2011
“I personally have received compensation for acting as an advisor to Biogen-Idec (BG12), Merck-Serono (Cladribine), Novartis (Fingolimod), Teva (Laquinimod) and Sanofi-Aventis (Teriflunomide).” I thought you worked for the …
Prof G,Any idea when it might become available?Is this another therapy which NICE will reject!To become an add-on, does it need to be trialed with another therapy (and take years before it can be used as an add-on)?
Re: "Any idea when it might become available?"Probably late 2012; or later in the EU and the UK.NICE does not have the power to reject drugs; all they rule on is its cost effectiveness for the NHS. If Biogen-Idec price the drug appropriately NICE will give it the thumbs up. I suggest we start lobbying now! I assume they will learn a lesson from the Fingolimod application; clearly £19,000 per year is too expensive.
Why add-on? Won't it work on its own?
Re: "Why add-on? Won't it work on its own?"Yes, it will work on its own, but not sufficiently well to suppress all disease activity. It may be a good drug to augment others, i.e. a different mechanism of action.
I don't think any of the drugs suppress all disease activity. As per http://www.reuters.com/article/2011/09/16/us-biogen-idUSTRE78F2PG20110916, BG12 results so far are about the same as Gilenya. If that is true, why are Gilenya and older (even less effective) drugs not being considered for add-on use?
Re: "… why are Gilenya and older (even less effective) drugs not being considered for add-on use?"Simple, without data we don't know if the combination will be better than either drug alone, or possibly worse. In addition, combination therapies make the costs of treatment very high; without cost-effectiveness data the NHS and insurance companies will simply not pay. I do however agree that BG12 is the one MS treatment that stands out as an ideal compound to be tested as a combination therapy.