Devoted to Men’s Health: Lessons Learned with Robert Dudley

Success happens at the convergence of passion, tenacity, collaboration, and significant unmet needs

How I got to where I am today feels somewhat serendipitous. With a PhD in pharmacology and toxicology, my background is in drug development and examining how drugs work. Early on in my career, I joined a small entrepreneurial company called Gynex Pharmaceuticals that had an interest in testosterone replacement. It was my first foray into the world of testosterone replacement therapy, which we fondly abbreviated to TRT. 

My initial work was on a sublingual testosterone product licensed from the NIH in the US, but its pharmacokinetic profile necessitated thrice daily dosing and the FDA was concerned about peak well above the upper limit of normal for testosterone. After a stint as VP of Clinical Development at a biotechnology company (BioTechnology General Corp.), I took a job as Vice President of R&D at Unimed Pharmaceuticals. It was here that I was approached by Besins Iscovesco (Paris, France) about developing a dihydrotestosterone (DHT) gel product as an androgen replacement therapy for men. Besins already had a DHT gel approved for use in France and Belgium but felt it could do well in the US. My response was, “Well, no – the FDA will not embrace a DHT gel because of concerns (at that time) about DHT’s potential role in prostate cancer.” Nevertheless, I went on to tell the company that I would be interested in collaborating with their team on a testosterone gel (T-gel) formulation...

Out of these initial discussions, AndroGel 1% was born and eventually approved by the FDA in 2000. I am really proud of this success. For such a small company to help develop the formulation, conduct all the clinical studies, and do everything else required to launch a product really is an amazing achievement. It was also a lot of fun! I guess history is the best gauge of AndroGel’s success; until AndroGel 1.62 percent gel came along, it was the top-selling testosterone product in the world. 

This was when I learned how important collaboration is. In our case, we were working with partners across an ocean, which demanded some flexibility. We also connected with some of the top academic investigators in TRT, and their expertise served as our base of operation from a clinical point of view. On a personal level, I made some incredibly dear friends – and mentors – who stuck by me through the whole process. As a result, I'm a strong proponent of using cross-functional teams aligned to do something pretty spectacular – whatever that may be.

Unimed also gave me the opportunity to move into the role of President and CEO (and at a public company) when my then predecessor left the company. From this position, I built the team to commercialize AndroGel and later, along with David Dodd (then president of Solvay Pharmaceuticals), I was the co-architect of the sale of Unimed to Solvay. After the sale, I remained President of Unimed until my decision to move back to the pharma startup world.

The good, the bad, and the ugly; honesty really is the best policy

As my career in pharma evolved, I became more aware of the fact that men with low testosterone have a seriously diminished quality of life – and it’s not just about reduced libido! These men have multiple issues that often sum up to a poorer quality of life. Moreover, the available therapies didn’t seem entirely optimized to patients’ needs – they simply weren’t designed to encourage patients to stay on their medication. After developing AndroGel, I left my role as president and CEO of Unimed Pharmaceuticals and started to consider what was still missing from the TRT marketplace. The answer: a safe and effective oral testosterone formulation that meets current regulatory standards for efficacy and safety. After all, oral medicines are more convenient for the patient than an injection or topical gel.

With that goal in mind, my current chief financial officer, Steve Bourne, and I began (literally) knocking on the doors of venture capital firms and pitching the idea. That’s how we started Clarus Therapeutics where we developed Jatenzo (testosterone undecanoate) capsules, CIII – an oral softgel TRT that was recently launched in the US after FDA approval in March 2019. 

But developing Jatenzo turned out to be a formidable task! After launching Clarus, we spent the first 18 months investigating something that didn’t work. I went back to our investors to admit our lack of success and to propose an alternative. The lesson here: be brutally honest. You need to be honest (with yourself and others) about where you are, so you don’t chase something that’s bound to fail. Our investors said they’d continue to back us, and we switched gears and worked to develop the successful formulation that would become Jatenzo. I believe that honesty was crucial in keeping our investors on board.

Drug development setbacks succumb to good problem solving

Setbacks come in all shapes, sizes and varieties; you need to get used to them in the business of drug development. For technical challenges, you must be a good problem solver. You have to get not only your own mind wrapped around the challenge, but also the minds and hands of other people who can help. Focus on the data; (generally) data don’t lie. And be flexible – expect to make some changes to formulation parameters to advance the product. 

You also need to get your development plan right and get into humans as fast as possible. There are all sorts of great animal models out there, but the animal that matters most when it comes to accurate results is the human.

Those three things – good problem solving, accurate testing, and speedy human trials – plus persistence, of course – are the lessons I’ve learned to achieve success. I've often used the analogy that drug development is like sailing into the wind. You just have to find a way to make forward progress until the winds come back around to fill your sails. Have faith that you can do it, and don’t give up as long as the business thesis remains sound. In the case of Clarus, despite our sometimes-daunting challenges, no other company came forth with an oral testosterone product and beat us to FDA approval. So, the market opportunity also remained strong. 

Don’t fear the regulator – you’re both on the same team

It has been a long, winding path to get Jatenzo approved by the FDA – a combination of internal development challenges and more rigorous evaluation requirements by the FDA that evolved during Jatenzo’s development. When it comes to the FDA, I have never lost sight of the fact that they have a tough job. I respect what they have to do very much, and I know they want the same thing we do: to make sure patients get the effective, safe treatments they need. Although I might not have agreed with all the hoops the FDA required Clarus to jump through for Jatenzo, I always viewed our relationship with the FDA as one of collaboration. We knew that we had to do our utmost to be responsive to their questions and requests and to maintain a good dialogue on what would be necessary to secure Jatenzo’s approval.

Our path to approval for Jatenzo was made more difficult by the success of the AndroGel franchise that ultimately ended up in Abbott’s (then AbbVie’s) portfolio. Here was a product that was heavily promoted in a direct-to-consumer campaign that the FDA and many physicians did not like – largely because there was concern that T-products were being over-prescribed. Beyond that, in 2014 and 2013, there were some controversial papers that indicated a possible cardiovascular risk associated with TRT. And so, the FDA started to look more closely at the TRT development arena, and, over time, they tightened regulatory requirements. When I developed AndroGel, it was a much less rigorous regulatory path than by the time I got to Jatenzo. As a result, I think we likely provided more data and information on our oral testosterone product than any TRT product before it. And we went before two separate FDA advisory committees during which the FDA explained that Jatenzo would likely change the landscape of TRT therapy and, thus, the need to make certain it was thoroughly reviewed.

Launching a new drug demands full-spectrum planning and top-notch execution

Upon approval of Jatenzo, our top priority was an excellent and well-executed launch. We launched the product in the US only a few months ago and we have worked hard to ensure that healthcare providers (HCPs) and patients are aware of Jatenzo and have access to it through their insurance plans. Access to prescription medicines are a big challenge worldwide, but, in the US, the insurance companies that oversee pharmacy benefits have become more selective about which drugs they cover, and how these drugs are included in the respective formulary plans.

We will continue to strive to maximize patients’ ability to easily access the medication in ways that are not a major hassle for their HCPs. The first year is all about establishing and growing momentum after the launch to build receptivity in the marketplace. Then, we’ll begin to look at additional projects that feed into lifecycle management. We believe there is still room to improve the treatment experience for patients – and we think that'll keep us very busy for the next couple of years!

Men’s health is rife with needs – and therefore, opportunities

Short-acting injections and patches were not the kinds of TRT products that men wanted, according to our market research. Jatenzo is a prime example of identifying an unmet need and addressing it. Looking at other diseases and health issues that affect men, I can see a lot of room for improvement. Inevitably, even incremental progress can make a big difference to patients. Consider testicular cancer – thanks to research and treatments, the cure rate is near 100 percent when it’s caught sufficiently early. Other cancers, such as prostate cancer, particularly refractory cancer that has metastasized, have not seen the same progress, but this may change given that many companies are looking at new treatment approaches.

Male contraception is another area where progress has been slow. That said, there are some really interesting studies coming out of the NIH and elsewhere that indicate that a male birth control pill could be closer than we initially thought. There is a significant group of the male population that would benefit from this form of contraception.

Beyond those, there is a cultural issue that affects men’s health. Many men simply avoid regular visits to the doctor, reluctant to admit they have a problem. Getting men to take better care of themselves is another unaddressed issue. This is especially significant in the big categories of cardiovascular disease, diabetes, and neurological issues, such as Parkinson’s and Alzheimer’s. Anything we can do to make it easier and more comfortable for men to talk about their health and get the help they need could go a long way toward reducing that reluctance.

At any given time, you may have no idea just how important your work is – keep at it

I was somewhat surprised by the success of AndroGel, even though I thought it was a major advancement in TRT when it entered the market. What I underappreciated at the time, and what epidemiology studies have since supported, is that testosterone deficiency is much more prevalent than had been assumed. In that context, it was all the more important to develop a product that would be used by appropriate hypogonadal men. Most types of hypogonadism that have structural or genetic causes require men to be on testosterone for the rest of their lives, so finding a convenient dosage form that encourages long-term compliance is crucial. And I hope Jatenzo will continue this story. Though our efforts with Jatenzo have been primarily focused in the US, we’ll be filing applications in the EU and in Asia over the next few years and also looking at other international opportunities. I think that’s exciting, and I'm proud of what my then colleagues and I accomplished with AndroGel – and even more proud of what team Clarus has done to bring Jatenzo to the market.

If you love your work, it will love you back

I love my work. I love the medicine. I love the science. I now have over 30 years of experience in this field, and it is hard to imagine stepping outside of it. I’m not saying that I wouldn’t, or couldn’t, change if the situation demanded it or the opportunity was interesting and challenging enough, but working in men’s health issues is a calling for me. I’ve managed to find a career that continues to fascinate and energize me; it makes me feel like I’m making a positive difference for men. If you can manage to find a way to reap such rich internal rewards, you’re blessed!