I made the case on behalf of DrK last month for a natalizumab Brain Attack Trial? I now have a personal clinical anecdote why we should not delay things any longer.
I saw a new referral in my MS clinic about 6 weeks ago. She was from an ethnic minority (red flag) with highly-active disease. Her imaging was very active but slightly atypical; she had a confluent lesion around the aqueduct that has been described in anti-aquaporin-4 positive patients with NMO spectrum disorder. I, therefore, delayed making the diagnosis to repeat her imaging, do a lumbar puncture and check her anti-AQU-4 results. As this, all occurred over the Christmas period it took 6 weeks for her to come back to me with all the results. In this period she has gone onto to have a very disabling brainstem attack. All her tests are back and confirm the original diagnosis of MS. If only I had started her on natalizumab whilst I was doing all the tests we would probably have prevented her having this attack.
She is now coming into hospital as an urgent admission for a course of intravenous steroids and to be started on natalizumab. Please note we have decided to start natalizumab without knowing her JCV serostatus. If she is JCV-ve we will leave her on natalizumab and if she comes back JCV+ve we will then decide on what DMT to transition her onto after a 12 month period of treatment.
What this patient illustrates is that MS activity tends to be clustered. A powerful predictor of a relapse is a recent relapse. The case for putting patients with possible early active MS at risk from having to wait is well illustrated in this example. Why don’t we to treat all patients like this with natalizumab to protect their brains and spinal cords while we complete their diagnostic work-up? This is analogous to treating stroke.
Why natalizumab? (1) It is one of our most effective DMTs, (2) it works very quickly, (3) it is given as an IV infusion, hence there is no problem with adherence and (4) it is very safe for up to 12 months. (5) It is also relatively safe in pregnancy. During this 12 month period, the neurologist and the patient can then decide what strategy they want to pursue in the long-term. This could be to continue natalizumab long-term or to switch to another DMT, or in the case of an alternative diagnosis the drug can be stopped.
To make the Brain Attack Trial a reality we need the EMA to license natalizumab as a 1st-line treatment. This will probably require data. Hence we are proposing that Biogen sponsor a ‘Brain Attack Trial’. This would become even more important if you can derisk the PML problem associated with natalizumab. Imagine if we can reduce the risk of PML to zero? Who wouldn’t want to start on natalizumab as a first-line therapy? Natalizumab will become the one and only platform therapy. The problem with this is that Biogen has other DMTs in the MS space and the Brain Attack Trial will potentially result in natalizumab cannibalizing their other DMT market. How bold is Biogen?