Tackling OCD From a Different Angle

Welcome to the Cutting Edge Cast From Russo’s Partners in New York.

Karen Chase: Constantly getting out of bed to check if the door is locked? Washing your hands again and again even when they're not dirty? Counting incessantly for no apparent reason? Negative terrifying runaway thoughts and fears that take over your mind and sometimes your actions?

These are some of the repetitive rituals and runaway emotions that people with obsessive-compulsive disorder (OCD) say they are powerless to stop.

Millions of people are affected by OCD - about 2% of the population. Yet traditional treatments targeting serotonin receptors in the brain, have left many patients untreated. 20-30% of people on these medications have reported problems. Saying they either don't work or cause side effects including weight gain and depression. Some have stopped taking them. But a potential new treatment in the pipeline could offer new hope.

BHV 4157 a drug candidate from Biohaven Pharmaceuticals takes a different approach and is now in Phase 2 testing at dozens of clinical sites across the country.

Dr. David Walling is the Principal Investigator of BHV 4157 at CNS in Garden Grove California, one of the dozens of sites.

Dr. Walling, tell us how scientists hope it will work and why it's different from traditional OCD treatments.

Dr. Walling: The Biohaven 4157 is a medication that's currently in development for obsessive-compulsive disorder. But different from other treatments for obsessive-compulsive disorder, this one works on what's called the glutamate system. So other treatments work on the serotonin system so a lot of times what's used for the treatment of OCD (obsessive-compulsive disorder) is a serotonin selective reuptake inhibitor or one of the antidepressants. But this one actually works on the glutamate system which is a completely different system in the brain. It's probably the major excitatory neurotransmitter in the brain, so dysfunction of this system is thought to contribute to lots of different disorders - anxiety disorders, OCD, potentially depression. And so that's the reason that I think the team is really excited about this medication. It offers the possibility of a completely new treatment for obsessive-compulsive disorder.

Karen Chase: Dr. welling how effective our current traditional treatments, how do patients feel about them?

Dr. Walling: So most of the currently approved medications to treat the obsessive-compulsive disorder are antidepressants. They work upon the serotonin system in the brain, and while for many individuals these may be effective drugs, what happens with these antidepressants is, we oftentimes have to use higher doses than we would use in the depression population in order to treat OCD. So we get up to these higher doses and what happens is individuals start to get side effects. And those side effects for some patients can really be intolerable. They can include things such as weight gain, nightmares, sexual side effects, all different types of things that people may not want to deal with, and so because of that we're always looking for new medications that can be used to treat OCD.

So, the Biohaven compound is working on a completely different system from the serotonin system. It's actually working on the glutamate system. And the hope is that for many individuals that have taken SSRIs or other antidepressants for treatment of OCD, that if it didn't work for them or if they had intolerable side effects, that this may offer a different option to help them to control their symptoms.

Karen Chase: Where is BHV 4157 in the research pipeline?

Dr. Walling: The current study with BHV 4157 is what we would call a Phase 2b/3 trial. And what this means is that the data that is obtained in the current study, so for the subjects that are participating in this study, this data could be used to potentially submit to the FDA for approval or as part of the approval process.

What many people don't realize is that there are multiple stages to the drug approval process. So a drug may start in Phase 1 which is early safety of the drug. And then we move to Phase 2 where we're looking at safety and efficacy, and then the larger trials are the Phase 3 trials that are really looking at efficacy and safety, and those are what is submitted to the FDA for approval. So this is what's considered a Phase 2b/3 trial. It could be used in either way, depending upon the data that is received in this study.

Karen Chase: What kind of candidates are you looking for in these clinical trials?

Dr. Walling: So, what's unique about this trial of BHV 4157 is that we're looking for subjects who have already received treatment with one of the current medications, one of the current antidepressants that are used for the treatment of the obsessive-compulsive disorder. But in the case of this study, we're looking for those individuals that have received that treatment but have not responded to that treatment so they had an inadequate response to one of the approved treatments for OCD. And so when you have a patient and you're treating them for OCD, about a third of patients, maybe a little bit more, continue to have debilitating symptoms, symptoms that interfere with their daily life that interfere with their quality of life their ability to do things and to engage with others and activities. And so we're looking for those individuals that have received that treatment but continue to have the symptoms interfering in their day-to-day existence.

Karen Chase: Tackling OCD from a different angle, BHV 4157 may become the first new treatment for OCD in decades. Those who want to know more about the clinical trials can find a location near them at OCDtrial.org.

You've been listening to the cutting-edge cast from Rousseau partners in New York. I'm Karen Chase.

Changing Minds: Challenges in Conducting OCD Research

When Biohaven began our OCD study last year, we expected there to be challenges in finding patients. But as our study team has many years of clinical research study experience, and a baseline knowledge of the OCD condition, we felt we had a pretty clear idea of what those challenges would be and how to address them. There are many recruitment support vendors out there, who specialize in reaching large numbers of people, and we used several of these vendors early on. But when this didn’t produce the results we expected, it was clear that traditional methods were not going to work, and that we would need a different approach.

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Right about that time, we were fortunate to become acquainted with a small start-up company called nOCD, and its founder Stephen Smith, who himself suffers from OCD. nOCD had developed a web platform and online community specifically tailored to engage OCD patients. After only a few conversations with Stephen and his team, it was absolutely clear to us what had been missing in our efforts to reach OCD patients.

What we had been missing was the voice of the patient. And it was only until we heard directly from people who are living with OCD, in their own words, exactly what their fears and concerns are about participating in a clinical trial, did we really understand what we would need to do to truly engage them. Everything from how they wish to be contacted (phone, e-mail, text message) to managing the fact that they may not return a call, due to anxiety, but may actually want to participate, if only someone would be persistent and call them back.

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This information was critical to our own understanding, and it also provided specific actions we could take in educating sites about how they interact with OCD patients. As much as we would like to believe that all sites approach recruitment with a deep understanding and empathy for the specific types of patients they are reaching out to, this is not always the case, and our ability to educate them was going to be just as important to the success of our study.

The study has been challenging, as we knew it would be, but it’s also been a journey in our understanding of OCD. We’ve learned that there is a huge difference between knowing what OCD is based on clinical descriptions, classifications, sub-types, etc. and hearing directly from OCD patients, in their own words. It’s a completely different level of understanding and speaks so clearly to how we all need to approach our work if we ever want to make a real difference in the lives of those who are truly suffering.