Corbus Pharmaceuticals Holdings Inc (NASDAQ:CRBP) just announced that the FDA has granted approval for a 12-month open-label extension study of the ongoing Phase 2 clinical trial of Resunab, its lead clinical candidate. The drug is currently in four separate trials across the US, and the latest extension relates to the systematic sclerosis (SSc) indication – an ongoing trial with topline set for release during the final quarter of this year. Extensions such as the one just granted can offer insight into the performance of a development stage drug ahead of topline. In turn, this insight might be valuable as far as forming a preemptive bias is concerned.
Here’s a look at the drug and the trial in question, as well as what the extension might mean for Resunab in the SSc indication going forward.
Resunab is is a formulation of what’s called ajulemic acid, which is in turn a synthetic derivative of THC. In our bodies we’ve got two types of cannabinoid receptors – CB1 and CB2. There are theories surrounding the existence of extra, novel cannabinoid receptors, but non are confirmed, so they’re not necessary to discuss for the purposes of this piece. CB1 receptors relate mainly to to the central nervous system – they are responsible for many of the psychoactive effects of cannabis use, for example. CB2 receptors relate primarily to the immune system. Their activation impacts the actions of certain elements of the immune system – T Cells, macrophages, etc. – specifically with relation to inflammation. This is great in healthy patients, as inflammation is a key component of the protective side of our immune system. Over activation, however, or overexpression, of these CB2 receptors can lead to a number of inflammatory conditions. Cystic fibrosis is one example. Lupus is another. SSc, which this news concerns, is a third. To simplify, Resunab binds to the CB2 receptors in a patient’s immune system. By binding to the receptors, they block these receptors from activation, and inhibit their ability to send messages to the nucleus of the cells with which they are associated. No messages means no effect. One such effect is inflammation, and this inflammation leads to the symptoms associated with SSc – skin, joint and organ fibrosis.
There are no currently available treatments for SSc, and there are circa 90,000 sufferers in the US and Europe, meaning it’s a big potential market for the company that can get a treatment to market.
So what does the latest news mean? As mentioned, there’s an ongoing phase II trialing the efficacy and safety of Resunab in an SSc indication. It’s a double blind trial, which we’ll talk a little more about shortly, with a patient sample size of 36 spread across 10 US sites.
Safety has been shown to be favorable in preclinical and phase I studies, with AEs like dizziness, vomiting and fatigue being the most prevalent, and only in low single digit percentages of patients across the doses being trialed.
The main focus, therefore, is the efficacy of Resunab in the current phase II, as measured through a primary endpoint of what’s called CRISS, or the combined response index for systemic sclerosis. We don’t yet know how the drug has performed, but the FDA approval of the open label extension gives us a clue. Why? First, what’s an open label extension? We discussed the double blind setup of the ongoing phase II a little earlier. Double blind simply means there’s a group of patients receiving Resunab, and a group receiving placebo, and no one knows which patients are in which arm. By changing this to open label, all patients will know they are taking Resunab, and patients from both arms will have access to the drug, even when the current trial is over. An optimistic analysts would argue there’s only really one reason that the FDA would allow this, and that’s that Resunab is performing well enough in the current trial (and has proven tolerable enough in the past trials) to warrant patients continuing their course of treatment. Not only this, but for those that haven’t yet started a course of Resunab (i.e. the placebo arm) to start doing so.
This is good for Corbus as it gives the company the chance to gather an extra twelve months’ worth of data in this indication, without having to recruit for a whole new trial. It’s good for patients as it allows them to continue on what they feel is an effective course of treatment. Its good for investors, as it offers a little bit of insight into the upcoming data release.
Of course, the FDA could just approve an extension based on the absence of non tolerability. If a drug is safe, why not allow patients to continue taking it? We’ve got to bear this in mind going forward – that the extension approval is an indication that the drug has demonstrated efficacy, but not a confirmation. It does suggest there are no serious AEs that have cropped up as part of the trial, however, and that’s positive in itself.
The takeaway? That the FDA approval of an open label continuation doesn’t confirm efficacy, but it implies it, and all but confirms tolerability. It’s a relatively small sample size, and we’re a couple of years from an NDA in this indication even with a successful topline release and – in turn – a replication of this success in phase III. This said, it’s an interesting development in a space set to draw considerable attention as topline starts to roll out towards the end of 2016.