Rare diseases have long posed a dual challenge. First, since there are relatively few patients by definition, they are not the highest priority for most drug makers. Second, many of them have proven quite difficult to effectively treat, let alone cure. The passage of the Orphan Drug Act in 1984 succeeded in spurring greater interest in the field. Amicus Therapeutics is one of the companies focusing on developing drugs for these hard to treat illnesses, one with a unique beginning.

Amicus was founded in 2002 and went public in 2007. Leading the company is founder and CEO John Crowley, who has a very personal stake in treating rare diseases. In the middle of an early, successful career at Bristol-Myers, Crowley’s children received a terrible diagnosis: Pompe Disease, a devastating neuromuscular disease. At that time, there was no treatment, so Crowley quit his job, co-founded his own company Novazyme, and then raced against the clock to find a way to help his children. In the end, Novazyme and later Genzyme worked to develop a successful enzyme replacement therapy that saved the Crowley children’s lives.

This real-life story has landed the Crowley family on the front page of The Wall Street Journal and served as the basis of the major motion picture “Extraordinary Measures,” starring Harrison Ford. In addition to his highly acclaimed career in the biopharmaceutical industry, Crowley also served as a commissioned Navy Reserve Officer who has served with a special operations team in Afghanistan. He graduated with a B.S. in Foreign Service from Georgetown University, earned a J.D. from the University of Notre Dame Law School, and also completed an M.B.A. from Harvard.

Once he’d succeeded in his mission to find a treatment for his kids, Crowley took time to contemplate what to do next. Reflecting on his personal experiences led him to build a new company focused on providing a patient-centered approach to treating rare diseases. This is what gave rise to Amicus Therapeutics, which is named for the Latin word for “friend” to represent the company’s commitment to be the most patient-focused and patient-friendly company in the industry. One key aspect of the culture is for employees to consider and make major decisions from the perspective a patient (or parent of a child) with a rare disease.

Although Crowley is optimistic about the current state and future progress of the industry, he identified three main obstacles to treating diseases in a way that serves the best interests of patients. The first is regulation. He praised regulators for moving quickly to work across many facets of treating rare disease, especially regarding incorporating patient voices into the process, but he believes that the regulatory framework has not kept up with the pace of scientific development.

The second major concern he has is policy. Specifically, policies that govern patient access to drug companies. Again, he identified the current state as mixed, with some policies (both current and proposed) really ensuring access to patients and others hindering it. “We need to ensure 100% access to all patients in need,” Crowley emphasized. “A number of us have tried to be pretty assertive with our views in terms of what will drive innovation and what’s in the best interests of patients in moving these medicines forward.” However, in his view, there’s still too much that hinders access.

The last major concern he has is the biopharmaceutical industry’s commitment to always acting in the best interests of patients. “We have a moral obligation to develop and manufacture the highest quality therapies for patients. We also have the obligation to ensure the broadest access [to needed medicines] possible,” he forcefully stated. He cited this year’s Gallup survey about public perception of various industries and organizations. “For the first time ever this year the biopharmaceutical industry ranked last. We ranked below the federal government and below Big Tobacco,” he said. He believes that the industry needs to improve how it serves patients or else this negative public perception will continue to impede the industry.

Shifting his focus from the industry at large to treating rare diseases in particular, Crowley also acknowledged significant challenges even as he maintained his overall positive outlook. Using Pompe Disease as an example, he stated that understanding a disease mechanism does not guarantee the development of a cure. Pompe Disease is an enzyme deficiency resulting in lost function. Replacing lost function is much more difficult in his view.

Though there is no cure, Pompe and Fabry now have treatments which Crowley considers an important initial step. “But there are risks and challenges inherent in any small disease population – recruitment of clinical studies for instance.  Even where we do have a first-generation approved therapy, sometimes the harder challenge is to come up with the next generation therapy.” He mentioned that the target for Pompe Disease is particularly tricky. And he cited that in some ways the Orphan Drug Act, while doing a substantial amount of good, has put up huge barriers to second generation therapies on top of the challenge of recruiting study participants.

However, he also cited that, despite the challenges, we are truly entering a golden age for medicine and technology. “35 years ago, before the Orphan Drug Act, there were just a handful of approved therapies for rare diseases. Today we have hundreds,” he said. “But it’s still been a tough fight. When we look at some of the results of these approvals in spinal muscular atrophy, in rare eye diseases, I believe we’ve finally turned the corner in gene therapy. When I look at gene therapies, RNA technologies, and also at the promise of a field like gene editing, over the next couple of decades we truly have the chance to change the course of disease and profoundly impact the course of human history to alleviate an enormous amount of suffering. That’s a great, great opportunity for us.”

How exactly does Amicus take advantage of this unique turning point? Crowley pointed to Amicus’ patient-centric culture as the key to making the strongest possible scientific and social impact. At the core of this effort is Amicus’ patient advocacy department. “Leading that effort is Jayne Gershkowitz, our chief patient advocate,” Crowley shared. “Her job is to be the voice of patients within the company and (along with the management team) the external face of Amicus to the patient community as well.” Even as the company has grown rapidly, it has stayed true to this commitment.

In the nearly fifteen years since its founding, Amicus has grown from five to 600 people across 27 countries while maintaining its patient-centric focus. Indeed, Crowley credited that focus for the company’s success thus far. Amicus has reached the commercial stage with Galafold, which is a precision medicine used to treat Fabry Disease.

“Beyond Galafold, in the last year alone we’ve built what is now the largest portfolio of rare disease gene therapies in the industry,” Crowley said. “We still have a very large vision. We decided years ago that at the end of our careers we don’t want people to look back on Amicus and think that we dreamed too small.” It’s a vision driven by the company’s fundamental commitment to patients.

Amicus is also currently pursuing a “second generation” treatment for Pompe disease: AT-GAA. “We think it has the potential to become the next standard of care. It is the crown jewel of our portfolio and the only ever second-generation therapy for any lysosomal storage disease to received Breakthrough Therapy Designation,” he stated. AT-GAA is designed to be more highly targeted to muscle cells. This protein with this glycosylation is highly phosphorylated. The mannose 6-phosphate receptor is the uptake mechanism. So, with the higher degree of phosphorylation Amicus has seen much higher penetration into muscles. It is combined with a small molecule to stabilize it in plasma, which appears add some stability and enhanced potency to the protein. Amicus believes that once it’s in the muscle it contributes to the breakdown of the glycogen that’s stored in muscles of Pompe patients.

To take this research to the next step Amicus is in the midst of their “PROPEL” study. This phase III study, which is due to complete enrollment by the end of 2019, looks at more than 100 adults living with Pompe Disease. “It is the largest lysosomal disease study ever conducted,” Crowley shared. “We are enrolling more than one hundred patients at more than eighty sites around the world on five continents. It’s also the most expensive study ever done in lysosomal disease field.” As a sign of their commitment to patient welfare, they’re now treating children and, to the best of their ability, meeting requests for expanded access or compassionate use of this still experimental treatment.

Being able to produce enough medicine to meet this demand is a challenge. Crowley credits Amicus’ success here (and indeed in many other areas) to excellent collaboration with its partners. “In some areas we needed the expertise and the infrastructure of partnerships, and I think the very best example is our partnership with WuXi AppTec, which began almost six years ago when we only had a cell line in Pompe. Once we saw the early results in animals, we knew manufacturing would be our greatest challenge at that point. And that’s where together with our teams at WuXi AppTec, we really built the processes, ultimately even facilities, geared toward scaling up this product.” Another challenge he cited was how to support the PROPEL study with commercial scale material. “Our team together with our partners and WuXi AppTec really rose to the occasion. It’s because of WuXi AppTec’s manufacturing capabilities that we’ve been able to answer so many [compassionate use] requests for AT-GAA.”

Crowley also cited their partnership with Dr. Jim Wilson and the University of Pennsylvania around gene therapy as being particularly important. “We combine our protein engineering expertise and technologies with the gene therapy and vector expertise of Dr. Wilson and UPenn.  And it has just been an extraordinary collaboration and partnership for us.” In this context he also mentioned Brammer (now part of Thermo Fisher Scientific) and Paragon (now part of Catalent) as keys to helping advance several of their programs.          

When asked what he would have done differently if he could, Crowley took the time to reflect back on his previous experience with Novazyme. “There we were laser focused on a specific medicine and developing a treatment for Pompe, getting into clinical studies. And that certainly was a noble pursuit. But there were times where I lost perspective of the big picture. Maybe it was partly because we were under such time pressure.” For Amicus he took a different approach.

“I instructed the team not to tell me what we’re going to do over the next couple of quarters. Instead I asked, ‘What do you want us to look like in ten or twenty years?’ I told them to dream and dream big. And then think about Amicus. And we ended up brainstorming and thinking really big. So, what I would have done differently is to lay out that bigger vision, that larger purpose to what we’re doing. I think that helps frame the smaller details.” He concluded by expressing his full confidence in his team to achieve these big goals. “We are a persistent and resilient bunch at Amicus.  And I think that’s a great trait for anybody in this industry.”

By 2030 Crowley is hopeful that we will get to a world with a complete understanding of mutations, universal (in the U.S. at least) childhood screening, and continuing growth in the number and efficacy of treatments – a world where parents can take full advantage of amazing new treatments to help their children avoid succumbing to an otherwise fatal disease.

That, he believes, is a world where we are truly putting the patient first.