Like a phoenix rising from the ashes for the third or fourth time, alemtuzumab is given yet another life. I am sure many neurologists and people living with MS will be grateful, but I don’t agree with its positioning.
EMA’s safety committee or PRAC has handcuffed alemtuzumab and is restricting it for adults with relapsing-remitting multiple sclerosis that is highly active despite adequate treatment with at least one DMT or if the disease is worsening rapidly with at least two disabling relapses in a year and brain-imaging showing activity. The new indication is not too dissimilar to that of natalizumab. Just when we are pushing for natalizumab to get a first-line license to address our #AttackMS concept, alemtuzumab gets yoked to natalizumab.
In my opinion, the contraindication handcuff that alemtuzumab must no longer be used in patients who have auto-immune disorders other than MS is not necessarily correct. I am not aware that having another comorbid autoimmune disease puts you at increased risk of developing another autoimmune disease after being treated with alemtuzumab. I have asked Joanne Jones and Alasdair Coles from Cambridge who have the most experience with alemtuzumab, both clinically and scientifically, and they agree. I think we need to appeal this contraindication as it may deny many pwMS access to one of our most effective DMTs. I suspect that Sanofi-Genzyme will have data from their trial programme to help appeal this contraindication.
Looking at this with from a glass-half-full perspective is the good news that at least we still have alemtuzumab as a treatment option for pwMS with more active disease. However, this will deny many pwMS with active MS from being treated with the most effective DMT first-line.
When will regulators come to the realisation that the decision to take on risks should be taken by the person with the disease guided by their HCP and not the regulators? By moving alemtuzumab to a predominantly 2nd-line position means pwMS will now have to wait several years to access the most effective DMT. I am not sure the new positioning of alemtuzumab in the therapeutic hierarchy will stop the more educated and determined people with MS seeking HSCT abroad or in the private sector.
I am curious to know if my letter to the EMA (below) helped. But having alemtuzumab back on the treatment landscape as predominantly 2nd-line therapy means we will at least be able to offer alemtuzumab as a realistic option before, or alongside, HSCT in London. This also means we can go ahead with our head-2-head comparison of alemtuzumab vs. HSCT to assess HSCT’s relative efficacy and safety against a licensed DMT.
Open letter the EMA sent on the 20th August 2019
European Medicines Agency
Amsterdam
Dear Sir/Madam
Alemtuzumab has transformed the MS treatment landscape. It not only provides superior short term efficacy, but a significant number of patients treated with alemtuzumab note improvement in disability. However, its main advantage over other DMTs is that a large proportion of patients go into longterm remission and normalise the rate of their brain volume loss. In regard to the latter, this is unprecedented in comparison to other licensed MS disease-modifying therapies, with the possible exception of haemopoietic stem cell transplantation (HSCT), which is not licensed and hence not widely available to treat patients with MS in Europe. Alemtuzumab, therefore, is the only realistic alternative to HSCT, which has become a very popular treatment choice amongst people with multiple sclerosis, in particular, ‘digital natives’ who get their information online. As with all DMTs the earlier you use them the more effective they are and the greater the benefit to the individual patient. Alemtuzumab is, therefore, an important treatment option for people with MS; being able to offer alemtuzumab early as a treatment option is an important factor in my clinical practice to dissuade many Britsih patients from travelling abroad for HSCT.
At our centre, Barts Health NHS Trust, we have now treated over 250 patients with alemtuzumab with over 40% being treated with alemtuzumab first-line. Patients receiving alemtuzumab first-line tend to have more active disease and less favourable baseline prognostic profile. Despite its side effect profile and the need for monthly monitoring, many patients are willing to take on the risks and the burden of monitoring to be treated with the most effective licensed DMT first-line. All our patients are extensively counselled about the risks and benefits of alemtuzumab treatment and sign an informed consent and a patient contract agreeing to the mandatory monitoring programme. We feel the use of alemtuzumab in the correct environment is relatively safe and the adverse events manageable. Not having alemtuzumab for use in early active disease would mean patients having to wait to fail several other, less effective, licensed DMTs prior to accessing alemtuzumab. I firmly believe in the concept that ‘time is brain and spinal cord’ in MS and delaying access to the most effective treatment would limit our ability to optimise the management of MS in patients with more active disease and in those with a poor prognostic profile. In addition, shifting the use of alemtuzumab to a population of patients with more advanced disease would unfavourably change the benefit-risk profile of alemtuzumab and make it less appealing as a treatment option.
The real-life data of alemtuzumab clearly supports it as being the most effective DMT on the market and its other attributes in relation to its posology make it a very appealing therapy; for example in women wanting to start or extend their families.
In summary, limiting alemtuzumab to a third-line, last resort DMT, will severely limit our treatment options for managing this devastating disease. Alemtuzumab offers many patients with MS a real hope of living as normal a life as possible, however, this option does depend on using alemtuzumab early in the course of the disease. I, therefore, appeal to the MS community and the European Medicine Agency to consider these factors when reviewing the benefits and risks of alemtuzumab as a treatment for MS.
Yours faithfully
GAVIN GIOVANNONI
CoI: multiple
I assume the nice guideline will be rewritten- any ideas how they’ll present the hierarchy now?
I suspect alemtuzumab will need to go alongside natalizumab and we will need to see if NICE revise their ocrelizumab STA. At the moment it states that ocrelizumab is only suitable for pwMS who can’t be treated with alemtuzumab.
Prof Giovannoni bless you, keep fighting for us, the letter you wrote to EMA means a lot, Alemtuzumab is now 2nd line treatment in Europe (most countries had it 3rd line), your advocacy must be spread, neurologists and pwMS must stand up and fight to make the best DMTs available for all.
Bless you
This is beyond frustrating. I am lucky enough to have been prescribed Lemtrada as a first line DMT. Why shouldn’t a patient be given access to the most effective treatment there is available for their disease? Why should we be forced to wait to deteriorate – to accrue more lesions and brain damage – to earn the right to be offered Lemtrada. I can’t image this approach being taken for people with other illnesses, so why MS?
As was my wife. Thank goodness we live in Australia where there are no restrictions on which DMT you can access first line…..for now.
I think that was a poor analysis by EMA , and it is a great damage for PwMs and for the specialists who take afraid about the security profile. The autoimmunity is a common condition for a lot of patients. In the case reports wasn’t a previous condition, and if it was, it wasn’t enough to concluded like a condition. Globally it’s a good new, but we back almost 10 steps!!!
I thought it would get pushed third line like in the USA. This is still bad news for the UK MS community. I wonder how long before the Australian regulators follow? My guess is not long.
What a shit show.
Having had MS for 14 years, with 8 years on Tysabri and having R2 of Lemtrada in January, I realise how lucky I have been after the EMA’s ruling to make it a 3rd line treatment. It is absolutely ridiculous that they have done this and I have and will always believe, that it is up to the patient to make an informed choice as to whether or not they have this fantastic treatment. It should not be for a regulator to make these decisions for people. That is down to the people who have to live with MS and it is up to them to weigh the pros and cons of it and decide whether they want it or not, not some faceless bureaucrat who thinks that know best. I was lucky that I took to it so well and my recovery after both rounds was much easier than most.
Agree with all the replies.
Seems silly but I almost feel guilty for having received Alem first-line as I had it in my early 50’s. There’s so many young PwMS who deserve to have accesss to the most effective treatment available, alongside HSCT. I’d managed to get into my late 40s (didn’t know had it then) before being knocked side-ways by my MS and our son was already at uni before I was diagnosed. For those who have the whole of their adulthood ahead, maximising their capacity to function as normally as possible as long as possible should be a priority.
Yeah it’s good Alem is at least 2nd and not 3rd line, but the EMA and the FDA needs to stop utilising, what I suspect, is the protocol that side-effects risks are given more weight than the accumulation of disability. Yes, let HCPs and PwMS work in partnership to decide what is best for each of them as individuals.