Most people know me as a huge cheering fan, but sometimes critical, of the pharmaceutical industry. Yes, I am a fan of capitalism and all the great innovations it produces for us. However, they are regulated by the government, which is in the habit of making us wait a long time. Nevertheless, this has been the most eventful period of development of new medications for MS, and we are waiting for some tremendous advances.
Three new and completely different medications are likely to be approved within the next year.
First up any day now: teriflunomide “Aubagio” is a daily pill which is closely related to an established and widely used drug for rheumatoid arthritis known as leflunomide “Arava.” In fact it is essentially the same (leflunomide becomes teriflunomide in the body). This medication has undergone extensive testing in MS, and at generally lower doses than in rheumatoid arthritis, with less other immunosuppressive medications, produces a satisfactory decrease in disability, relapse, and MRI activity. It is not spectacular, but it is fairly simple. It will be marketed by Genzyme which is owned by Sanofi. The upside it works, the downside is that it is complicated to use in women who become pregnant, and immediate action is required to get the drug out of the body to reduce the risk of birth defects; about 1/2 of children exposed in the first two months of pregnancy have multiple minor defects (these are not usually serious). It is also important to monitor for depressed white blood cells “neutropenia” which is an established and not rare complication of the drug. Liver complications are much less significant. Serious infections were not a problem at the doses used in the trials. Unfortunately, a significant fraction of patients become allergic to the drug (as many as 10-15%) and cannot take it further. Some hair loss can also occur.
All in all this good. It is an immunosuppressive medication which hits rapidly dividing cells, and whether long term there is more risk is not clear. MS patients generally have less of these complications due to the factor they do not take multiple immunosuppressive medications like RA patients.
I think Genzyme/Sanofi has a challenge. If they price it too high, it won’t be used, and leflunomide is still out there and is essentially the same drug (really, for practical purposes it is the same drug). If you want to know more about this drug, go to the prescribing information for Arava/leflunomide. The active metabolite, which is discussed at length, is teriflunomide.
Up second by 1st qtr 2012 is a real game changing drug. Alemtuzumab/”Lemtrada”, formerly known as CAMPATH. Also being marketed by Genzyme/Sanofi and copromoted with Bayer Healthcare. This is the most powerful drug ever seen in MS. It also has some significant medical risks, but the vast majority of people treated do not have a major complication. This a bioengineered targeted “magic bullet” monoclonal antibody for which TWO Nobel prizes have already been awarded. It has been researched in MS for over 20 years and the therapy was invented by the brilliant professor Alastair Compston at Cambridge University. I think he deserves a Nobel as well. It will save the lives of many, many people with worse than average MS.
Alemtuzumab basically makes the immune system reboot by wiping clean a great fraction of the immune cells “lymphocytes” which are the dysfunctional, misbehaving cells causing MS. It induces wonderful remissions after two once-yearly treatments (IV 5 days the first and 3 days the second). It stomped a very good MS medication (high dose interferon-beta or Rebif). Most people do not need further MS treatment for years. Mild-moderate infections, mostly minor nuisance infections (yeast, ringworm, shingles) can occur in the months following treatment, but the immune system is amazingly intact.
The down side–people feel run down a few weeks after the annual cycle. A large amount of surveillance blood testing is needed because a large fraction (25%) will develop some kind of thyroid problem, usually overactive (hyperthyroid). A few percent have this severely and feel bad for an extended period of time and need radiation therapy (radioiodine) to treat a severely overactive thyroid. A few percent also can get a temporary bleeding disorder called acute ITP, which if detected early on a blood test is simple to treat with prednisone. Both of these illnesses, and a few milder and rarer ones occur, because the immune systems of people with MS are capable of generating immune cells which react against many of the bodies organs. About 1/3 of MS patients develop thyroid disease in their lifetime anyway.
So trading severe MS for an annoying minor thyroid problem is a good deal. Moreover, alemtuzumab is the first medication which reliably IMPROVES disability in MS patients.
Our clinic has been a leading center in research worldwide in this treatment. It seems to work for even the most severe MS.
Last of all, coming 3rd qtr 2013, there is the medication with a sexy name “BG-12” (doesn’t have a brand name yet), but is dimethylfumarate, owned by the little engine er company that could, Biogenidec, the powerhouse of MS research. This drug is a simple chemical, used for decades for psoriasis in Germany, which seems to have two fascinating properties- it trips the sensor cells use to tell they are being stressed by oxygen, and this turns on the systems (nrf2) which quelch damage from oxygen and chemicals, which helps in MS because the inflammation is doing this harm. An added bonus is it throws the circuit breaker on the inflammation by blocking a powerful inflammation inducing signal (NFkappaB). So, this is a completely new class of drug. The closest thing to it, believe it or not, is broccoli (mostly the sprouts), which contains a chemical called sulfurophane, which also does this. You don’t want to have to eat enough broccoli (pounds a day).
The data on dimethylfumarate evoked a “WOW” last fall at the ECTRIMS meeting, and again at AAN this spring, where it stomped Copaxone, besting it by another 50%. This drug seems to have very little toxicity (none), except it causes a bellyache which doesn’t go away in about 10% of people, and those folks can’t take it. There is occasionally some nuisance flushing which decreases with aspirin. We don’t have more than about 3 years of data though. That said, it looks pretty safe. The only other drawback..it will be a twice a day pill.
Having been involved from early in the development of this dimethylfumarate, I like this drug very much. It could fundamentally change how we treat MS, provided the manufacturer prices it appropriately and the long term data continues to look safe.
All these medications will have a role. Alemtuzumab will have the biggest impact as it adds a nuclear weapon to our arsenal, literally making it the last medication someone may ever need. It is not a cure, but the closest we will see in the next 10 years. Patients and doctors will have to swallow hard and accept the risks in order to get the benefits, but the vast majority will get off without anything more than inconvenience.
The other pills will have to see both longterm risk, and how the manufacturers price them. Hopefully, they will not make the mistake drug giant Novartis made pricing their products in the stratosphere, which made it impossible for people to get them in many cases.
The existing medications will be used. For a substantial number of people they are safe, reliable, and already doing the job.
People with MS are going to be switching treatments more, and their paths and options are going to be more individual.
Samuel F. Hunter, M.D., Ph.D. is a neurologist specializing in neuroimmunology and neuroimaging, and has a remarkably broad background in pharmacology, image analysis, medicine, and neurosciences. He directs the Advanced Neurosciences Institute, Novel Pharmaceutics Institute, and NeuroNexus Center for research and education in Franklin, Tennessee, a suburb of Nashville. He participates and directs a multiple sclerosis clinic and many research trials for multiple sclerosis and its related conditions. He consults or performs contract research and consults for many pharmaceutical companies. Dr. Hunter has previously been a consultant for many pharmaceutical companies.
Copyright 2012, Dr. Samuel F. Hunter
by SAMUEL F. HUNTER, M.D., PH.D. on JULY 25, 2012