Alagille Syndrome
Conference Roundup

From Concept to Clinical Trial: Developing Treatments for Rare Diseases

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From basic research through drug discovery, preclinical work in animals, clinical trials in humans, and then regulatory approval, therapeutic development is an often complicated, controlled process said Lara Longpre, Chief Development Officer at Mirum Pharmaceuticals during a presentation at the 2023 PFIC Family & Scientific Conference.

“This looks like a very linear process,” Mrs. Longpre told the audience, “But it doesn’t actually happen that way.”

The start of the process begins with basic research, drug discovery, and then preclinical work, which can take anywhere from 3 to 6 years.

Basic research, Mrs. Longpre said, is trying to understand the disease at a molecular or genetic level. From there, you go to drug discovery. In the old days, she said, this was often done by accident, like with the discovery of penicillin. Today, however, more modern methods are used to try to find something that’s going to address the disease process.

“Once you understand the disease, then you can try and figure out how to fix it, and that’s what the drug discovery is about,” she said. “Very few molecules, products, or drugs will make it past drug discovery into the preclinical research.”

From the point of drug discovery forward, it takes an average of 10 to 15 years and around $2.6 billion to develop a drug.

Once something is discovered that might treat the disease, the next step in the process is to test the drug in animals.

“We’re looking at how the drug moves through the [animal’s] body. We’re looking at whether it’s safe, whether it works, trying to figure out what dose to use, how to administer it. All these types of questions begin to get answered at this early stage,” Mrs. Longpre said.

After making it through animal testing, the next step is to test the therapeutic in humans. There are 3 main phases in clinical trials for humans. Phase 1 studies typically enroll only a handful of patients—maybe 10 to 30—and may take days or weeks to complete, with the primary focus on safety and understanding how the drug is interacting with the human body.

“It may look safe in a mouse, but a mouse doesn’t always translate to a human,” she said.

About 70% of drugs pass from Phase 1 trials to Phase 2 trials, where more safety in more patients if the focus, this time in up to hundreds of patients. Phase 2 studies can take weeks or even years to be completed.

“In addition to expanding our knowledge on the safety, we’re looking for the first time to see does this drug really work,” Mrs. Longpre said. “So, from this point, maybe about 25% of drugs move into Phase 3.

Phase 3 trials typically enroll hundred to thousands of patients and look to confirm the findings from Phase 2 as well as ask what they can learn from previous trials, such as dosage or patient populations.

“We take all those learnings from Phase 2, bring them to Phase 3, and try to confirm our understanding of the safety and whether the drug works or what has efficacy.”

Phase 3 trials can last several years and only about 20% of drugs will make it past this stage. Mrs. Longpre said that when you include all the drugs that move through the process, only about 5% make it to market from when you first started in animals, and costs around 2.6 billion to develop a new drug.

As for the timeline of clinical trials, it can take about 10 to 15 years.