We believe new treatments are transformational when talking about protozoal disease. What inspires transformational thoughts and ideas? Some think it is a mysterious process, right out of the blue, a light comes on. More likely, innovation springs from many years of questioning, hard work, vigorous testing, and careful analysis.
We have reached the proverbial 10,000 hours (ref: Malcolm Gladwell, Outliers) studying EPM, creating models, and we are ready for a final analysis. Our research started using models that defined the disease process and indicated that we could develop a beneficial treatment. Years later, it’s time to put the models aside and statistically test our model. Our first placebo controlled study for NeuroQuel is available, limited to 60 horse owners. This is a study that will be part of our Freedom of Information Summary and because it is an FDA study it has a few strings attached.
NeuroQuel is a drug that is designed to control the residual or recurrent clinical signs due to inflammation associated with Equine Protozoal Myeloencephalitis (EPM) following antiprotozoal therapy in horses. The field study will enroll horses that have failed to improve, or have relapsed after licensed EPM treatment (Marquis, Protazil, or Rebalance). The horses will receive NeuroQuel and we will evaluate the response to the treatment.
This is a placebo controlled study. The first form, the Owner Consent form, is required. The owner consent form informs the horse owner that there is a chance (a statistically calculated chance, 1 out of 3) that the horse will receive a placebo treatment. Your horse will not be considered for entry into the placebo controlled study without this form in place. If you haven’t signed this form, you are not in this study.
Does the horse qualify for enrollment? Not surprising, the documentation for qualification is called the Qualification Record. There are three conditions that must be met to qualify 1) the horse was previously diagnosed and treated for EPM. 2) The animal exhibits recurrent or residual clinical signs with a minimum of a Grade 2 deficit, and the easy one 3) the animal is 6 months or older weighing 600 pounds or more. A Grade 2 deficit is defined as “a defect that is easily detected and exaggerated by backing, turning or neck extension. The horse may sway at a walk. There may be a wide based stance after tight circling. The horse is weak on the tail pull-easily pulled off track and does not return to a normal walk for 3 steps.”
There is a second part for the qualification into the study. There are situations that will un-qualify a horse. The horse can’t be in another study or unsuitable for this study. The horse can’t enroll if it has another disease. If the horse can’t get up, or the owner can’t get medication into the horse (or multiple folks will treat the horse) it won’t meet the qualification criteria.
There are some other forms to fill out, the Physical Exam form, the Data Collection form at day 0 and day 14, and a Supplemental History form (these document the criteria used to support the original diagnosis of EPM). There is a blood draw before and after treatment, the blood is collected in a couple of red top and lavender top tubes, accompanied by a Sample Collection form. Owners participate in the observations by completing check boxes on the Client Observation form for behavior, appetite, respiration, and occurrence of diarrhea. Additional space is provided for owner comments.
So far, so good. But the first inclusion criteria is the most difficult requirement for this study. The original diagnosis of EPM must be supported by testing and other diagnostic testing as needed. The FDA set the standard as CSF analysis to support the original diagnosis. After bioassay for antibodies in the CSF the horse must have received a full course of an FDA approved treatment, per label instructions: dose, duration, and frequency, no loading doses or multiple treatments. Treatment must be what the sponsor intended when they licensed their treatment. Treatment must be within 90 days of enrollment. At the end of the FDA approved treatment, if signs (minimum Grade 2) are present, then the horse will qualify for this study. Also, if within 90 days the horse “relapses” with a Grade 2 deficit, then the horse will qualify for the study.
We recognize that CSF taps are not generally obtained in the field and most veterinarians test serum, or don’t test at all. We strongly hold that testing allows the selection of the correct treatment and can be accomplished by serum testing. Hopefully data from this study will support that rationale, CSF taps aren’t the best criteria to determine a horse that will respond to treatment.
However, until there is a paradigm shift at FDA, we provide a CE course (3 credits) and teach a technique to obtain a CSF tap, in the field, in a standing horse. Field sedation techniques, using drugs most veterinarians have on hand, allow a veterinarian to get a CSF sample from the neck. With a bit of practice, the tap can be obtained in a couple of minutes. You can email us for the link or go to the Learn More tab and copy the link from the slide presentation that describes Pathogenes CE program.
We will continue to use models that advance our ideas because idea-modeling will result in more treatment options for horses and their caretakers. For example we learned about the effect Sarcocystis fayeri, a common protozoal infection in horses, can have on neuromuscular disease. Another example is the presence of autoimmune disease in horses, when treated early the horse can have several more years of useful life. A limited enrollment, placebo controlled study gathers statistical data. After the “reasonable expectation” of clinical benefit study a conditional license is issued and a larger field effectiveness study is conducted.
We are far from finished and need your to help in these studies if new equine treatments are desired in the pipeline. From idea to models to field use, it’s expensive and time consuming. It’s highly rewarding. This is our commitment to the horse community and any part you can play is appreciated.