We in the U.S. looked on in dismay as Norway ponied up some major krone (Norwegian dollars) for a large Rituximab ME/CFS trial while the mighty U.S. medical establishment sat on its hands. It wasn’t just weird – it was embarrassing. Here was a potential breakthrough in a disease that everyone in the federal establishment said is a priority for them – yet not a finger was moved. When even Simon Wessely asserted that Rituximab should get a trial – and the U.S. still stayed mute –  something seemed very wrong

Norway funds a RItuximab trial and the U.S. does not? Say what?

In retrospect the reason seemed clear: the federal government doesn’t do drug trials – they are the purview of the pharmaceutical companies. In the U.S. the marketplace rules. If you can get a drug company to pay for a drug trial you have a shot. If you can’t get a drug company to do that you’re out of luck…

That sounded right ( it made me feel a bit better but in fact it was completely wrong). The National Institutes of Health (NIH) does fund drug trials and it’s doesn’t just fund a few of them – it funds lots of them.

In retrospect that only makes sense. Why would the biggest medical research funder in the world leave the fruits of its labors – treatments – entirely in the hands of drug companies? Why would it leave the marketplace entirely in charge of such a vital factor? It wouldn’t and it doesn’t. The National Institutes of Health spends a nice chunk of change on drug trials every year.

The Missing Piece

That only begs the question, though, why two small but successful Rituximab trials were not enough for the NIH to step in? Or why Ampligen – which the FDA now says is safe – and only needs further confirmation of its efficacy – is still sitting by the wayside?

The answer seems to be that neither chronic fatigue syndrome’s current home, the Office of Research For Women’s Health, nor it’s parent, the Office of the Director, funds clinical trials. From what I can tell only the Institute’s fund clinical trials and ME/CFS, of course, is not in an Institute (yet).

Four ME/CFS Trials

Why is the NIH funding trials in other diseases but not ME/CFS? One reason – ME/CFS is not in an Institute

I can think of four drugs or drug combinations in ME/CFS urgently looking for funding. The Pridgen Protocol would certainly qualify for fibromyalgia.

• Ampligen
• Rituximab
• Synergy methylphenidate/supplement combination
• The drug combination uncovered by the Biovista Solve ME/CFS Initiative project

Ampligen – the Greatest Concern

Ampligen is probably the greatest concern right now. Norway is funding a major Rituximab trial and Invest in ME in the U.K. is on track to fund another, but Ampligen – which doctors strongly support – is basically on life-support. Hemispherx cannot afford the studies the FDA requires and the marketplace is not stepping up.

Ampligen’s producer – Hemispherx Biopharma – recently cited needed laboratory upgrades as a reason to more than double Ampligen’s price in the U.S. That’s obviously going to present a severe hardship to the couple of dozen or so patients taking it in the U.S. More than anything else, it underscores the need to get this drug approved.

Rituximab – the Breakthrough Waiting (and Waiting) to Happen

Rituximab is the other biggie. It’s an expensive drug that requires long drug trials but it did very well in two small studies. Given the drugs popularity it’s not surprising that some Institutes are funding Rituximab trials.  What is surprising is how many they are funding.

The National Institute of Neurological Disorders and Stroke (NINDS) is funding one for myasthenia gravis and the National Institute of Allergic and Infectious Disorders (NIAID) is currently funding  four Rituximab trials (Anti-cytokine Autoantibody-Associated Diseases, lupus nephritis, Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH) and renal transplantation. NIAID recently completed Rituximab trials in diabetes (which it is not responsible for), kidney transplantation, lupus and Sjogren’s Syndrome.

The myasthenia gravis trial stands out because it’s funded by the National Institute of Neurological Disorders and Stroke (NINDS) for a rare disease (<75,000 people /U.S.). This year-long trial will take place in no less than 26 locations and include 50 people. (ME/CFS researchers work at or have worked with several of the study locations (University of Alabama at Birmingham, Emory University, Columbia, Ohio State University, University of Utah). It will finish up about the time the Norwegian Rituximab trial finishes up.

These trials are not anomalies.

The National Institute of Neurological Disorders and Stroke (NINDS)

Talk has been swirling that National Institute of Neurological Disorders and Stroke (NINDS) is interested in ME/CFS. If you want to get a drug trial funded you could do worse.

NINDS funded around 60 drug trials this year

A search on Clinicaltrials.gov suggests NINDS probably funded somewhere around 60-70 clinical trials this year. It funds several different kinds of trials. It seeks to find new applications of FDA approved drugs (gabapentin – fibromyalgia) or it funds studies of entirely new drugs (E-selectin – stroke, AAVD2-GDNF – Parkinson’s). It funds trials on its own or in collaboration with a drug company or hospital or other entity.

In fact, NINDS is so interested in exploring new treatments that it’s begun a separate initiative called NeuroNEXT (Network for Excellence in Neuroscience Clinical Trials) whose goal is to “respond quickly as new opportunities arise to test promising treatments”. NeuroNEXT recently created a clinical trials methodology course to assist junior investigators in developing the best clinical trials.

Some NINDS’ Sponsored Clinical Trials for 2015

These are NINDS sponsored clinical trials that popped up in the first three pages (of a seven page result) of a search on Clinicaltrials.gov.

• Guanabenz in multiple sclerosis
• The effects of magnetic stimulation on motor functioning
• Idebenone for Primary Progressive Multiple Sclerosis
• Levetiracetam in Oromandibular and Cranial Dystonia
• Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency
• E-Selectin Nasal Instillation to Prevent Secondary Stroke
• Methylphenidate – Traumatic Brain Injury
• Functional Electrical Stimulation – Stroke
• Anakinra – Neuroinflammation in HIV
• Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
• scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy
• Neurofeedback in Stroke
• Raltegravir for HTLVI
• AAV2-GDNF for Advanced Parkinson s Disease
• Deep Brain Stimulation for Movement Disorders
• Acthel for Cushing’s Disease
• Dac Hyp for Multiple Sclerosis
• Surgery – Intractable Epilepsy
• …….

National Institute of Allergic and Infectious Disorders

If NINDS’ slate of clinical trials is impressive, NIAID’s slate is off the charts. A NIAID search brought up fifteen pages of results – about twice as many an NINDS. (Many of these are not actually clinical trials)

• Vaccine (FSME-IMMUN 0.5 mL Baxter) Against Tick-borne Encephalitis (TBE) for NIAID Workers Manipulating Tick Borne Encephalitis Virus (TBEV) in the Laboratory
• Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency
• Bone Marrow Stromal Cells for Inflammatory Bowel Diseases
• Single ZMappTM Administration in Healthy Adult Volunteers (Ebola drug)
• Benralizumab in Subjects With Hypereosinophilic Syndrome
• AVI-7100 Flu Drug in Healthy Volunteers
•  Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa Loa Infection
• Imatinib Mesylate to Treat Myeloproliferative Hypereosinophilic Syndrome
• Elite Controller and ART-treated HIV+ Statin Versus ASA Treatment Intervention Studies
• Dengue Vaccine (TV003) in Healthy Adults, Adolescents, and Children in Thailand
• ……..

National Institute of Arthritis and Muscoskeletal Disorders (NIAMS)

In 2007 NIAMS reported that a 150 person NIAMS funded double-blind trial found gabapentin could be helpful in fibromyalgia. (Interested in having NIAMS fund your study? Use this application here.)
NIAMS is even funding studies on HIV and diabetes – neither of which it is responsible for. Some of the trials NIAMS is currently funding, co-sponsoring or collaborating on include:

• PPAR-y Anonists in Immunomodulation and Vascular Prevention in SLE

• TNF Alpha Inhibitors in Rheumatoid Arthritis
• Omalizumab for Lupus
• Resistance exercise in juvenile rheumatoid arthritis
• JBT-101 in Subjects With Dermatomyositis
• Strength Training in Duchenne Muscular Dystrophy
• Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma
• Nelfinavir in Systemic Lupus Erythematosus
• Allopurinol in Inflammation, Endothelial Function, and Blood Pressure
• …….

The FDA

The FDA was nothing but hostile at the Ampligen hearing, but since the Patient Conference they’ve been very helpful in helping to legitimize ME/CFS. Their acknowledgement that ME/CFS is a serious disorder on a par with diseases such as heart and kidney failure surely is helping to change the conversation about ME/CFS in the federal government.

The FDA does help fund drug trials – for rare diseases. They allocated $14 million for funding drug trials into rare diseases in 2015, and they expect to increase funding numbers over the next couple of years.

The FDA is funding trials for rare diseases that get no help from drug compannies…Why not ME/CFS as well?

ME/CFS is not a rare disease but it’s in much the same situation as rare diseases: it has large unmet drug needs and few, if any, drug companies are interested in producing drugs for it. The FDA apparently simply didn’t believe or envision that common disorders would not get interest from the drug companies. If they had they might have created a pathway for funding to flow to them.

The FDA official overseeing the ME/CFS program – Janet Woodcock, however, is one of the top officials at the agency. If anyone could get the FDA to commit funds to support an ME/CFS drug trial she could.

The FDA is continuing to get pressure to do something about Ampligen. A slate of ME/CFS experts recently called on the FDA to hold a two day conference to assess and find a way to get beyond the hurdles Ampligen faces there. They now recognize that the drug is safe; their only concern is efficacy – and proving that in a larger trial.

Conclusion

The NIH regularly funds drug trials but only, it appears, at the Institute level. That, of course, leaves ME/CFS out of luck. Moving into an Institute could, however, give ME/CFS  a shot at getting one of its urgently needed drug trials funded. The bottom line is that ME/CFS needs to be in an Institute not just to get better research funding but to get help with drug trials.

The FDA also funds drug trials in diseases that drug companies aren’t interested in.  The catch is that they are rare diseases. ME/CFS is not a rare disease but it is in the same boat that rare diseases is in. The FDA has the right idea with the rare diseases program; it simply needs to apply that idea to ME/CFS.

Ampligen is one medium-sized trial away from being the first FDA approved drug for ME/CFS,  and the Institutes regularly fund Rituximab trials. Both drugs would be strong candidates for NIH/FDA funded drug trials should ME/CFS get into an Institute.