PracticalDermatology

Can you discuss the significance of interleukin pathways as they relate to the treatment of
psoriasis?

The interleukin-17 (IL-17) pathway has the potential to promote inflammatory processes and appears to play a central role in the pathogenesis of psoriasis. The IL-17 family of proteins, or cytokines, are produced by immune cells, including helper T cells. These cytokines are important for normal immune function, and are believed to play a role in protection against specific fungal and bacterial infections.

In psoriasis, abnormal immune function may trigger overactive helper T cells and overproduction of IL-17 cytokines, leading to excessive proliferation of skin cells and other inflammatory responses, such as itchiness and redness. Multiple IL-17 cytokines, such as A, F, and A/F, have been implicated in the pathogenesis of psoriasis. Therefore, blocking the activity of the IL-17 pathway could impact the inflammatory process; more specifically, blocking the IL-17 receptor has the potential to inhibit the action of multiple IL-17 cytokines, and could potentially reduce inflammation, excessive skin cell development, and skin thickening.

Could you offer a brief synopsis of brodalumab’s mechanism of action and what separates it from other IL-based psoriasis treatments both on the market and in the pipeline?

Brodalumab, a novel human monoclonal antibody, is the only investigational treatment in development that is thought to inhibit inflammation by binding to the IL-17 receptor, thereby blocking the binding of multiple IL-17 cytokines (including IL-17A, IL-17F and IL-17A/F) that are key drivers in the development of psoriasis.

The data so far for brodalumab has been very encouraging—can you place the current data in context and offer your take on where it will fit within the scope of biologic therapies?

The brodalumab Phase III clinical trial program is comprised of three pivotal AMAGINE studies that include more than 4,200 patients with moderate to severe plaque psoriasis, all of which showed positive results and met their primary endpoints. In particular, AMAGINE-2™ and AMAGINE-3™ met all primary endpoints showing superiority to Stelara® (ustekinumab, Janssen) in achieving total clearance of skin disease. AMAGINE-2 and AMAGINE-3 together are the first and largest clinical studies to share head-to-head results against Stelara in psoriasis.

AMAGINE-1 assessed the safety and efficacy of brodalumab compared with placebo in patients with moderate-to-severe plaque psoriasis. It met all primary and secondary endpoints evaluating brodalumab compared with placebo.

Based on results from these trials, and the existing unmet need for higher levels of skin clearance, we believe brodalumab could be an important new treatment option for the many people living with moderate to severe plaque psoriasis. We believe patients need to have access to a variety of treatment options, given that not everyone responds to treatment the same way.

Head-to-head studies are fairly uncommon in this field, particularly when they involve an investigational agent and an already approved agent. Can you discuss the significance of the brodalumab/ustekinumab trial and its findings?

The AMAGINE-2 and AMAGINE-3 trials, comparing brodalumab with Stelara (ustekinumab), together are the first and largest clinical studies to share results against a current standard of care in psoriasis. AMAGINE-2 and AMAGINE-3 are identical in design and duplicate studies were conducted to provide substantial clinical evidence to understand the efficacy of brodalumab relative to placebo and Stelara. These studies provided insight into the relative efficacy of targeting different targets in the immune system.

Both AMAGINE-2 and AMAGINE-3 met all primary endpoints showing superiority to Stelara in achieving total clearance of skin disease.

With these data, we now have insights into how brodalumab compares with ustekinumab in more than 3,600 patients. These results further confirm our belief that brodalumab can offer significant benefit for psoriasis patients by targeting the IL-17 receptor to inhibit inflammatory signaling.

Since you co-authored many of the brodalumab studies, would you be able to identify any nuances or particular details about this agent that you feel are noteworthy that may be of some interest to prescribing physicians?

Based on results from these trials, and the existing unmet need for higher levels of skin clearance, we believe brodalumab could be an important new treatment option for the many people living with moderate to severe plaque psoriasis. We believe patients need to have access to a variety of treatment options, given that not everyone responds to treatment the same way.

Can you give a preview of what’s ahead in terms of new research/data in coming months?

We look forward to sharing detailed results from the AMAGINE Phase III clinical trial program at upcoming scientific meetings.

Can you reflect on the current state of psoriasis treatment and what the next big steps/hurdles will be in terms of achieving optimum outcomes?

There are a variety of treatment options available to those living with psoriasis, yet many patients still do not meet their goals. New treatments are needed to address this gap. We also believe that patients need access to a variety of treatment options, given that not everyone responds to treatment in the same way, and that there remains a significant unmet need in helping patients reach higher levels of skin clearance.

Based on results from the AMAGINE program, we believe brodalumab could be an important new treatment option for the many people living with moderate to severe plaque psoriasis. n