Stories of progress, inspiration, and information in overcoming osteosarcoma.

Overcoming the 4 Biggest Challenges in Drug Development for Rare Diseases

Fernanda Arnaldez, MD, explains that small sample sets, disease complexity, and limited funding pose challenges in rare disease drug development, but the field is rapidly evolving, making her optimistic about the future.

The Food and Drug Administration (FDA) defines a rare disease as one that affects fewer than 200,000 people per year. For osteosarcoma, that rate is even smaller — about 1,000 new cases of osteosarcoma are diagnosed in the U.S each year. Children and teens represent about half of those cases.

Of course, osteosarcoma does not feel “rare” to families affected by it, as it is the most common primary bone cancer. More effective osteosarcoma therapeutic interventions are desperately needed.

Fernanda Arnaldez, MD, a Strategic Advisory Board member at the Osteosarcoma Institute (OSI) and a senior global product leader for AstraZeneca PLC, explains that despite the many complexities of drug development today, creative and collaborative solutions are on the horizon.

Challenge #1: Limited Data

Rare disease research and development is typically supported by smaller datasets. Acquisition of relevant biological samples continues to be a key priority to advance preclinical science.

Dr. Arnaldez says there is ample cause for hope, though. Within the patient community, there is an effort to crowdsource data to widen the sample set available to scientists. Osteosarcoma data gathered through the TARGET initiative is widely available to scientists, and a number of other groups are actively sharing clinical data, genomics data, protein data, and pathology images — breaking down the barriers to effective scientific progress.

Challenge #2: Fewer Clinical Trials

Even after a scientist has discovered a promising treatment, a smaller patient population makes it harder to assemble a demographically diverse clinical trial to test the drug’s safety, tolerability, and efficacy.

“It sounds simple, but when your numbers are very small, it is not that easy,” explains Dr. Arnaldez.

However, physicians, scientists, and regulators are pushing innovation to run clinical trials that are efficient, fast, and with high data quality. An example of this is how the measures of “success” (endpoints) have evolved from overall survival (OS), progression-free survival (PFS), or tumor measurements (overall response rate — ORR) to start including “surrogate endpoints”: biomarkers, quality of life, and other functional measures.

Challenge #3: Disease Complexity

Drug development for osteosarcoma is especially challenging due to the complexity of the disease. “Few diseases in oncology can be cured with one agent and one agent only. We are working to figure out what is the best strategy to use the most efficient combination of the available treatments in sequence, in parallel, intermittently, or continuously.”

“The more we learn about different molecules, different mechanisms, and different strategies, the more insights we will uncover that could be applicable to diseases that we never thought of.” — Fernanda Arnaldez, MD

In this arena, Dr. Arnaldez is excited about strides forward in artificial intelligence. As computer technologies advance, researchers are using machines to analyze available data and potentially generalize new patterns. She says, “There is a possibility that we could envision patterns of response, patterns of toxicity, or other features of the behavior of different molecules within therapy, that we would not see with the naked eye.”

Challenge #4: Limited Funding

Dr. Arnaldez explains that without adequate funding, none of this groundbreaking work can be done.

“That is why institutions like the OSI can make a huge difference,” Dr. Arnaldez says. “The more we learn about different molecules, different mechanisms, and different strategies, the more insights we will uncover that could be applicable to diseases that we never thought of.”

The scientific landscape is evolving quickly, leveraging advances in technology and new ways of collaboration and data sharing. Combined with the dedication of organizations like the OSI, Dr. Arnaldez remains positive. “Advocacy is being leveraged to increase our knowledge about osteosarcoma,” she says. “So there is a whole lot of hope out there.”