Bloomberg Law
Jan. 4, 2021, 7:07 PMUpdated: Jan. 4, 2021, 8:55 PM

FDA Aims to Ease Single-Patient Trials for Rare Disease Drugs (1)

Jeannie Baumann
Jeannie Baumann

More clinical trials for patients battling life-threatening genetic disorders could open up under an FDA proposal for developing drugs targeting the exact DNA misspellings causing the disease.

The Food and Drug Administration issued draft guidance Monday to help researchers design and pursue a type of “N of 1" clinical trial, in which a single patient is the entire study population. The guidance outlines how and when to talk to FDA staff and keep information confidential. It also discusses ethical reviews and consent requirements.

N of 1 studies come with a unique set of challenges. A single academic researcher, who hasn’t navigated the FDA’s drug development process the way a pharmaceutical or biotech company has, is usually running the study. These scientists are often racing against time to fight a rapidly progressing disease.

Patrizia Cavazzoni, acting director of the FDA’s Center for Drug Evaluation and Research, called the draft guidance a first step in working with those who are developing individualized drug products.

“If we have the scientific ability to develop drug products for these rare diseases, we need to find a way to bring them to patients while ensuring there is the right balance of risk to benefit,” she said in a statement.

Breakthrough Potential

Advances in testing and diagnoses at the molecular level have allowed researchers to pinpoint the exact cause of diseases and develop drugs tailored to the genetic variant. Those advances hold the potential for breakthroughs for 25 million to 30 million of Americans suffering from about 7,000 known rare diseases, many of which can be traced to changes in a single gene.

“This is an important advance in treatment for those with very rare genetic diseases, especially those for which there are no adequate therapies available to treat the disease,” Cavazzoni said. “Often, these very rare diseases are rapidly progressing, debilitating, and in many cases, can lead to premature death if left untreated.”

The draft guidance focuses on drugs that use small pieces of RNA or DNA to block genes from making the proteins that cause the disease. It’s the most advanced area in individual genetic drug development so far, Cavazzoni said. Researchers are studying whether these drugs can work on several types of cancer by blocking cell growth.

“The learnings that will come from this work will ultimately bring benefits, not only to the patients living with these extremely rare genetic diseases, but to broader patient populations as well,” Rachel Sher, vice president for policy and regulatory affairs at the National Organization for Rare Disorders, said in a statement.

Edward Abrahams, president of the Personalized Medicine Coalition, said the draft guidance shows the FDA is exploring how to integrate these treatments into the future of medicine. “‘N-of-one’ therapies represent an enormous opportunity to advance clinical care, though they are not without regulatory and financial challenges,” Abrahams said in an email.

N of 1 studies have already shown some promise. Boston Children’s Hospital scientist Timothy Yu used an N of 1 trial to repair the genetic mutations that caused then 6-year-old Mila Makovec’s particular form of Batten disease—a group of rare nervous system disorders.

“No question that platforms for ‘individualized’ medicines are coming,” Yu told Bloomberg Law. “This procedural guidance from the FDA marks the beginning of an important conversation about how to extend the capabilities of our medical system for many with unmet needs, especially for those with very rare conditions.”

CDER Director Janet Woodcock said last year the agency was rushing to make “cookbook guidelines” for more scientists who want to pursue individualized treatments. Woodcock stepped away from the FDA last spring to take a leadership role with the Trump administration’s Operation Warp Speed Covid-19 vaccine development program.

(Updated with comment from Yu in 12th paragraph.)

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To contact the editors responsible for this story: Fawn Johnson at; Alexis Kramer at