Healthcare giant Roche Holding (SIX:ROG) just announced that it has picked up priority review for its lead hemophilia asset. When a company gets a priority review nod, the time it takes for the FDA to form a decision as to the outcome of a New Drug Application (NDA), or a Biologics Licensing Application (BLA) as is the case here, is reduced from the standard ten months to six. It also often comes in combination with a breakthrough designation, which in and of itself brings with it a spate of advantages related to the regulatory process and post approval commercialization and marketing.
This is a market with a considerable unmet need so the outcome of the review process could make a real difference to topline, even for a company the size of Roche. As such, markets are going to be watching the outcome of the review very closely. If it's favorable, Roche could pick up a nice bump in market capitalization.
So what are the chances of the company picking up a regulatory green light?
Let's take a look.
As mentioned, the drug is a hemophilia target and it's called emicizumab. In hemophilia, patients have a deficiency in what's called factor VIII, which is a clotting factor that (as its name suggests) plays a key role in the clotting of blood. It's a genetic disorder (caused by a dysfunctional gene that's supposed to produce factor VIII and either doesn’t produce enough of it or produces dysfunctional version of it) and it can be extremely serious – if a patient cannot stop themselves bleeding through the standard clotting process, they can bleed to death on the back of a small cut or otherwise insignificant trauma.
Some patients also develop inhibitors to factor VIII. These patients might produce enough of the clotting factor but the inhibitors render it useless, which has the same end-impact in this group of individuals.
Data has shown that emicizumab has the potential to treat both of these groups of patients – those that don't produce enough functional factor VIII and those that naturally create inhibitors that stop functional VIII doing its job.
Said job is the binding to two other coagulation factors, one called factor IX and another called factor X. Emicizumab binds to both and is able to mediate the activation of the latter, performing the function that would normally be carried out by factor VIII.
So how strong was the data on which the BLA is based?
The numbers derive from two phase III studies, one called HAVEN 1 and the other called HAVEN 2, both of which investigated the potential of the drug in patients that have hemophilia type A with inhibitors. HAVEN 1 looked at the drug in adults and adolescents while HAVEN 2 looked at the drug in children.
For HAVEN 1, the primary endpoint was treated bleeds, and results showed a statistically significant and clinically meaningful reduction in bleed rate of 87% with emicizumab prophylaxis compared with on-demand treatment with what are called BPAs, or bypassing agents.
For HAVEN 2, after a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. In this population, that's an incredibly strong result.
The drug was relatively well tolerated but, as many reading might already have read elsewhere, a small number of patients suffered from what are called thromboembolic events or developed thrombotic microangiopathy (TMA) during the clinical development program. One of these patients died after suffering a serious rectal hemorrhage followed by TMA.
There's some suggestion that the TMA events are due to the above mentioned BPAs, as opposed to the active investigator drug. Indeed, in this instance, The investigator analyzing the patient death concluded that the drug wasn’t the cause of the death, which means that the asset has a relatively clean safety profile to support the above discussed efficacy numbers on its application.
So, let's bring all this together and try to answer the question posed above – what are the chances of the company picking up a regulatory green light?
In short, very high. Aside from the just discussed death (which was deemed not to have been caused by emicizumab) the program was nice and smooth. Efficacy looks to be established well beyond reasonable doubt while safety shouldn’t be a problem, especially given the lack of valid treatment options that exist in this space right now.
Analysts put peak sales for this one at $5 billion; that's what's at stake here. PDUFA comes in at February 23, in line with the priority review.