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As rare disease drug development increases, Javier Szwarcberg, MD, MPH, CEO of Spruce Biosciences, discusses the challenges in this space, and how his background is helping him find solutions for patients, specifically with endocrine disorders.
Pharm Exec: What is your experience in rare disease?
Szwarcberg: For the majority of my professional pharmaceutical career and forming years as a physician, I have chosen to focus on rare diseases. This began early in my career during my fellowship in Pulmonary and Critical Care at Mount Sinai Health System, where I worked closely with my mentor Dr. Alvin Teirstein researching sarcoidosis, a rare disease characterized by the growth of tiny collections of inflammatory cells (granulomas) throughout the body. Following my fellowship, I continued to work in rare diseases at Washington University in St. Louis, where I created and ran the Interstitial Lung Disease Clinic with a focus on pulmonary fibrosis.
Wanting to apply my skillset more broadly and have an impact in the lives of more patients, I decided to pivot my career and entered the pharmaceutical industry. My passion for rare diseases continued and fueled my professional trajectory forward. I spent time at a number of companies focused on rare diseases with real unmet need, including: severe asthma at Aventis, idiopathic pulmonary fibrosis (IPF) at InterMune, and primary pulmonary hypertension and HIV at Gilead Sciences. I went on to serve in executive positions at Raptor Pharmaceuticals; Horizon Pharma; Ultragenyx Pharmaceutical; BioMarin, in clinical development, business development, and heading product and portfolio strategy; and now Spruce Biosciences, to complete my full immersion into rare diseases.
I am excited to bring my experience to Spruce and lead a strong team advancing novel therapeutics for rare endocrine disorders, including congenital adrenal hyperplasia (CAH)—a rare disease that has not benefited from a new treatment in over 50 years. I look forward to being a part of this progress and helping move the needle for the broader rare disease community.
Pharm Exec: What have you learned about the space from your vast experience?
Szwarcberg: Throughout my career as a physician and scientist leading more than 22 clinical trials for a variety of drugs, I have learned about the importance of true patient centricity—especially for rare disease—and the perseverance and relentlessness needed at every step when building a rare disease pipeline in-house. Rare diseases are often overlooked due to the perception of a smaller market and commercial opportunity, meanwhile patients are suffering and keep waiting for medicines that never come. However, advancements in science with new modalities inclusive of gene therapies, RNAs, antibodies, and conjugated molecules, coupled with a more agreeable FDA and an investment community that appreciates the opportunity, are all making the dream of addressing many of the over 7,000 rare diseases a reality.
Pharm Exec: What are the greatest challenges in developing drugs in the rare disease space?
Szwarcberg: There are a number of challenges when it comes to developing new therapies in the rare disease space, but some of the top challenges include:
Pharm Exec: How did you become involved with endocrine disorders?
Szwarcberg: I initially got involved in the endocrine disorder space when working for Horizon Pharma, where I was part of the team who in-licensed teprotumumab from River Vision for thyroid eye disease (TED). I was very interested in the clear biology of endocrine disorders and biomarkers that enable early readout to prove mechanism of action. I later went on to work with the burosumab program for X-linked hypophosphatemia (XLH) while at Ultragenyx, and with vosoritide for achondroplasia while at BioMarin.
Now, as CEO of Spruce Biosciences, I have the privilege of working on clinical programs for adults and children with classic CAH and for women with polycystic ovary syndrome (PCOS). There is a vast unmet need in the rare endocrine space, and patients have not benefited from the innovation that other disease areas have seen. It’s very meaningful to be able to apply my background and knowledge to potentially help patients who lack adequate treatment options.
Pharm Exec: What is the current standard of care for people with CAH, and why hasn’t there been much progress over the years in developing new therapies?
Szwarcberg: The current standard of care for individuals with CAH is chronic, lifelong glucocorticoids (GC) to replace missing cortisol and control the hyperandrogenism within these patients. Patients with CAH take above physiologic doses of steroids to keep the hyperandrogenemia under control, which have long-lasting and unwanted consequences both in children and adults. Because CAH is diagnosed via newborn screening, patients are put on steroids from birth, so it is the cumulative dose that matters. Early in life, individuals face side effects such as weight gain, Cushing’s syndrome, acne, anxiety, and short stature. Later in life, these concerns shift to cardiac complications, metabolic syndrome with hyperinsulinemia, bone loss, obesity, anxiety, and concentration issues.
Unfortunately, patients with CAH face a difficult choice between the detrimental effects of living with chronically high adrenal androgen levels or accepting the compromise of supraphysiologic doses of GCs. This dilemma has persisted for approximately 50 years. That’s why corticosteroid-sparing therapies that reduce the chronic GC burden are greatly needed. Now that the long-term toxicities of cumulative doses of GCs are being realized by patients and providers, and the unmet need in CAH is becoming further evident, more companies are conducting research into the space.
At Spruce, we are working to change the treatment paradigm by providing a novel solution. We are pleased to be in late-stage clinical studies with our wholly owned product candidate tildacerfont, which represents a non-steroidal CRF-1 receptor antagonist approach with the potential to improve disease control and lower elevated ACTH levels and adrenal androgens, while reducing the need for higher doses of steroid for patients with classic CAH.
Pharm Exec: How do you see treatments for these patients changing in the next five to 10 years?
Szwarcberg: Through innovative research and cutting-edge science, we have the potential to bring much-needed relief to patients and families challenged by the current standard of care in CAH. My hope is that CRF-1 receptor antagonists will transform the treatment paradigm and that, over the next five to 10 years, practitioners will transition away from supraphysiologic doses of GCs to manage their CAH patients and move toward physiological replacement levels only.
These should result in less short- and long-term side effects of exogenous steroids and result in patients living fuller lives. I’m proud to be leading the team at Spruce composed of caring drug development professionals, and I am inspired every day by the work we do to improve the therapeutic options for patients and families living with CAH.