Pfizer Kicks Off Phase 3 Trial for Rare Disease Gene Therapy

January 11, 2021 - Pfizer recently announced that the first participant has been dosed in the Phase 3 study to evaluate the safety of its investigational rare disease gene therapy candidate in boys with Duchenne muscular dystrophy (DMD).

The trial will enroll nearly 99 ambulatory male patients aged four through seven years across 55 trial sites in 15 countries, Pfizer said. The first patient was dosed with the candidate, PF06939926, in Spain at the end of December.

“The initiation of our pivotal trial, which is the first Phase 3 DMD gene therapy program to begin enrolling eligible participants, is an important milestone for the community because there are currently no approved disease-modifying treatment options available for all genetic forms of DMD,”  Brenda Cooperstone, MD, chief development officer of rare disease at Pfizer global product development, said in the announcement.

“We believe our gene therapy candidate, if successful in Phase 3 and approved, has the potential to significantly improve the trajectory of DMD disease progression, and we are working with worldwide regulatory authorities to initiate this program as quickly as possible in other countries,” Cooperstone continued. 

The trial, CIFFREO, is a multicenter, randomized, double-blind, placebo-controlled study. The primary endpoint of the study is change in baseline in the North Star Ambulatory Assessment (NSAA) at one year.

The NSAA, according to Pfizer, is a 17-item list that measures gross motor function in boys with DMD. Eligible participants are scheduled to receive PF06939926 at the start of the study or after one year following treatment with a placebo. 

The participants will be followed for five years after treatment and will receive commercially representative drug products manufactured at Pfizer’s gene therapy manufacturing facility in North Carolina.

“DMD is a progressive disorder, and patients and parents are waiting desperately for treatment options,” said Silvia Avila, president of the Duchenne parent project Spain. “The initiation of this study is an important step forward for this community, and it fuels us with hope that one day there may be treatment options for boys impacted with this devastating disease.”

In May 2017, Pfizer received orphan drug and rare pediatric disease designations in the US for PF06939926. 

The company also received fast track designation from FDA in October for the rare disease gene therapy based on Phase 1 study data that indicated that dystrophin expression levels were sustained over a year. 

DMD is a rare genetic disease that generally affects males and causes the muscles in the body to become weak and damaged over time. It is eventually fatal. 

Specifically, DMD stops the body from producing dystrophin, a protein that muscles need to work properly. Some of the effects that children face include trouble walking and trouble breathing. 

Eventually, the muscles that help to breathe and the heart, will stop working. 

According to Pfizer, nearly 140,000 boys are affected with DMD worldwide and 30,000 in the US and Europe. And although gene therapy for DMD is an active area of study, many of these therapies are still in development. 

One gene-based method, such as Sarepta Therapeutics’ drug, eteplirsen, uses a process called “exon skipping” to produce usable dystrophin protein, FDA stated. Essentially, eteplirsen  “skips” over the part of the gene that causes an issue with the muscle proteins.

In exon skipping, more muscle protein is usable, although it is shorter than the normal protein, the agency said.

In mid-August, FDA granted accelerated approval for Viltepso, an injection for the treatment of DMD in patients who have confirmed mutation of the DMD gene that is amenable to exon 53 skipping. 

The approval was based on two clinical studies, which showed that dystrophin increased, on average, from 0.6 percent of normal at baseline to 5.9 percent of normal at Week 25.