We asked industry leaders and academic researchers in the fields of hematology, pain, HIV, and neurology what they see as the major obstacles holding back the development of new drugs today.

What do you see as the biggest barriers in drug development today?

Len Valentino, hematology researcher at Rush University Medical Center and President of the World Federation of Hemophilia USA

The greatest challenge for drug development is meeting the expectations of the people that will use the drug or the product. Having been in industry, my colleagues and I would create what's called a target product profile, where the target is the patient, and the profile is how we're going to create the product that's going to meet their expectations. We would work to understand the population of people that we want to use the product and then design the characteristics of that product that would be attractive to that population. Then, we would work backwards from that target product profile. I think drug developers don't necessarily do enough work to truly understand what the goals and desires of the population are. They do this after the fact, where they say, “I've got a compilation of data” and then they try to convince patients that this is good for them. In contrast, if they went in with the understanding of what's important to the patient and what's going to make someone use this in terms of efficacy and safety, then they could design a trial that creates endpoints and data that support that change. It would be much more compelling to be able to present that to people, and they would naturally gravitate toward the product.

John McDonough, Chief Executive Officer and Executive Chairman at Sunbird Bio

Across disease states, we are witnessing incredible advancements in drug development, due in great part to the growing understanding about the range of biomarkers involved in various diseases. However, the pace of advances in certain disease categories has clearly lagged due to a lack of precise and available diagnostic tests. In neurological diseases in particular, the dearth of diagnostic tests that can comprehensively, accurately, and accessibly detect all of the proteins and other biomarkers that we now know contribute to the pathology of diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) has severely impacted the speed and success of therapeutic development. This includes detrimental impacts on clinical trial design and targeting, patient stratification for trials, monitoring of therapeutic efficacy, and appropriate treatment adjustment. Diagnostics that reflect our current knowledge of disease and enable a more precise view of patients’ neurological health would allow for accelerated discovery, development, and availability of more effective new therapies and finally bring neurology into the era of precision medicine.

Steven Cohen, anesthesiologist and pain researcher at Northwestern University

In the field of pain, it's that animal models don't translate well. We're not really measuring pain in animals. We're measuring behaviors that we think are associated with nociception, but we're not asking animals how much something hurts. If we measure cancer or tumor growth or blood pressure or blood sugar, we can actually measure those things directly. So, that's part of the problem. The other thing is that a lot of these targets only address one component of pain. They address what used to be called the sensory discriminative component of pain — how fast nerves fire. But there are other components of pain, like the affective, motivational, or the emotional component of pain. There is also something that's been described as the cognitive evaluative component of pain, which includes aspects like catastrophization, and it includes someone’s understanding of pain and what their expectations are regarding prognosis. There's much more nerve firing after surgery, for example, because the body doesn't have a chance to modulate the signals. But it's much better tolerated pain-wise because there's not as much anxiety or concern about what's going to happen compared to a cancer diagnosis. Somebody might have mild pain, and then they're diagnosed with cancer. It's a terrible thing, but nothing has changed from the time they didn't have a diagnosis to the time they were diagnosed. A lot of the pain models neglect these other components of pain: the affective or emotional component and the cognitive component.

David Margolis, infectious disease researcher at the University of North Carolina at Chapel Hill

In the area of HIV, therapy has gotten about as good as it can get. It's nearly a perfect therapy. Now, the major developments are just working to turn one pill-a-day therapy into long-acting therapy, with one injection every two months or one pill per month. And then the other areas of HIV drug development that are focused on preventive vaccines and cures is also very challenging. Our classic academic approaches are helpful to make advances scientifically, but the techniques and the skills and the infrastructure to actually develop drugs and therapeutics is not always present in academia. And it’s not necessarily rewarded or funded. The NIH recognized this a long time ago, and they have used various public and private partnerships to try to advance areas where there's this translational gap that started in HIV cure research at the beginning of the effort and led to the funding of these research groups called collaboratories. We are one of the collaboratories at the University of North Carolina at Chapel Hill, and there has been 15 years of funding. We’re about to enter year 15, and we're waiting to find out if the collaboratories will be funded for another five-year term. The collaboratories have had industry partners working with them, but it's an increasingly challenging area for partnerships.

Ketan Mehta, Founder and Chief Executive Officer at Tris Pharma

We are at an important inflection point in developing and delivering novel therapies that safely and effectively treat acute and chronic pain. Against the backdrop of an enduring and devastating addiction epidemic — still with millions of people suffering from life-impacting pain that is not well managed — the biopharmaceutical industry is rising to the occasion and working with urgency to deliver needed pain medicines, while facing reasonable skepticism from those impacted by and treating pain. We and many others in the industry view the barrier of regaining the trust of patients and physicians not as a challenge but an opportunity. It will take time and a meaningful commitment to transparency from the industry.

Some responses have been edited for length and clarity.