Multiple myeloma, lung cancer, and Lyme disease have little in common with alpha-1 antitrypsin deficiency (AATD). But Scott Santarella’s 25-year career as a nonprofit executive has involved all these diseases—an experience that has proven invaluable for Santarella, who now heads the nation’s largest organization for people with AATD.

Scott Santarella
Scott Santarella, president and chief executive officer of the Alpha-1 Foundation in Miami, Florida. (Photo by Larry Luxner)

As president and chief executive officer of the Alpha-1 Foundation, Santarella advocates for some 10,000 patients with this rare illness in the United States alone, and perhaps 100,000 worldwide. Passed from parents to children through their genes, AATD can cause serious lung disease in adults, and possibly liver disease at any age.

“Our biggest challenge is in detecting and diagnosing the disease properly,” Santarella told Rare Disease Advisor by phone from the foundation’s headquarters in Miami, Florida. “That’s one of the areas we’re trying to focus on, and we’re hoping to do that over the next couple of years so that we can identify more patients that need our support.”

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Santarella recently addressed the 2022 Rare Diseases & Orphan Products Breakthrough Summit in Washington, DC. He said access to augmentation therapy—also called replacement therapy—for underserved populations has been a major issue, especially since the pandemic began.

“The therapy is administered by a weekly intravenous infusion; it’s considered ongoing and lifelong,” he said.

“With COVID, the challenges became greater because oftentimes patients have to be treated at a clinical resource center. Those centers were closed down, so patients were at times not able to get therapy or had to rely on home infusions.”

More Than $90 Million for AATD Research

Santarella said his group is pushing for insurance companies to permanently cover home infusions—even after the pandemic is long over—as this has been shown to benefit patients who can’t easily access infusions otherwise.

Safety had never been an issue for most of the Alpha-1 Foundation’s 20 years in existence, he said, “but in the last 2 years, we had patients who were afraid to get care because of COVID.”

“What we know is that if you stay on therapy, you feel better, you’re healthier, your lungs don’t deteriorate as much,” he said. “You can live somewhat of a normal life with the disease, although it’s not the normal life that someone like you and I would experience with normal lungs.”

To date, the Alpha-1 Foundation has funded over $90 million to support AATD research at 123 institutions in North America, Europe, Australia, and the Middle East, though it has raised considerably more than that since the organization’s inception in 1995. Much of those funds are spent on mouse studies, with the goal of eventually getting into human studies and trials.

The foundation is also investing directly in biotech companies “that have therapies that we think look promising as a way to try to encourage new and innovative ideas into our market space so that we can continue to provide patients with options,” he said.

According to the foundation, 36% of the charity’s funding comes from corporate contributions. Alpha-Net contributes another 29%, while investments bring in 24%; the remaining 11% comes from “other support.” Major industry partners that fund Alpha-1 include CSL Behring, Eversana, Grifols, and Takeda.

Developing Therapies More Quickly

One area of interest is the development of an inhaled plasma-derived therapy. Kamada, an Israeli company that won US Food and Drug Administration (FDA) approval in 2010 for Glassia®, an alpha-1 proteinase inhibitor and the first liquid plasma-derived product to treat AATD, is currently working on such an inhaled therapy it says could potentially revolutionize the treatment of AATD.

Laboratory assistant Asher Moshe, an employee of Kamada in Rehovot, Israel. Credit: Larry Luxner

“The concept is promising. Obviously, taking an inherent inhaled medication versus an intravenous medication provides a tremendous amount of improvement in quality of life and certainly, perhaps, in the types of side effects that you may encounter or other issues when you’re talking about intravenous,” Santarella said.

“I think there’s still a lot of work to be done on whether or not the inhaled medication dosage can get into the lungs deep enough and have the impact that intravenous therapies have,” he added. “I don’t know if one particular therapy is going to solve this AATD puzzle.”

Meanwhile, the Tucson, Arizona-based Critical Path Institute (C-Path) has formed a partnership with the FDA to develop AATD therapies. The venture, known as CPA-1, will “define tangible unmet needs in drug development for AATD and lay the groundwork for specific solutions to these needs,” an October 6, 2022, press release said.

“FDA is partnering with C-Path to launch a pre-consortium collaboration aimed at addressing the need for clinical development tools in alpha-1 antitrypsin deficiency,” announced Celia Witten, PhD, MD, deputy director of the FDA’s Center for Biologics Evaluation and Research. “There is a clearly demonstrated need for development of new treatments in this area and we believe that collaboration across stakeholders working toward this goal has the potential to help accelerate progress in the field.”

Santarella said the CPA-1 venture will cut the drug development process for AATD treatments from 3-5 years to around 18 months “because we have all the data, we know the stakeholders, and we have all the information. We’ve been doing this for 20 years, and in our minds, we’ve uncovered everything there is to uncover.”