Industry analysts were shocked when in July the FDA reversed course on Amicus’ Phase III treatment for Fabry disease.
Industry analysts were shocked when in July the U.S. Food and Drug Administration reversed course on Amicus’ Phase III treatment for Fabry disease less than a year after the agency stunned Amicus when it called for a new clinical trial for migalastat.
The reversal paved the way for Amicus to file its New Drug Application for migalastat yesterday. The company said the NDA is based on existing clinical data, as well as the totality of data from two Phase III pivotal studies. But, there may be more to the reason Amicus was able to file the NDA this year.
This week, the Project on Government Oversight alleged that friendship and flattery may have had a lot to do with the course reversal. David Hileznrath, an investigative reporter with POGO, filed a report that allege Amicus Chief Executive Officer John Crowley directly appealed to newly appointed FDA Commissioner Scott Gottlieb just days after he took control of the agency. Crowley sent Gottlieb a handwritten note that was congratulatory and also alluded to previous conversations the two had regarding migalastat.
“As discussed, the hopes and well being of so many living with rare, devastating diseases rests now with your great leadership and wisdom,” the note said, according to POGO, which obtained the note following a Freedom of Information Act request.
In seeking a new trial, the FDA said it was interested in additional safety data on gastrointestinal (GI) symptoms in Fabry patients who have an amenable mutation. Fabry disease is a rare genetic disease caused by the lack of an enzyme that allows the body to break down lipids, which are fat-like substances that include oils, waxes and fatty acids. Without the ability to break down the enzyme can lead to kidney problems as well as heart attack or stroke. The disease affects about 10,000 people globally.
Crowley and Gottlieb had a history through the FDA commissioner’s former role as a venture partner with New Enterprise Associates. The venture capital company was a major investor in Amicus, POGO reported citing filings with the U.S. Securities and Exchange Commission.
In addition to the attached handwritten note was a more formal letter seeking a repeal of the 2016 rejection. In the formal letter, Crowley said there was no time to conduct another clinical trial as it would take five to seven years. Although that differs slightly from earlier statements made by the company that a new trial would take about three years.
A few days later, the letter was then sent by Gottlieb’s office to “a staff member in the FDA unit that had called for the additional study,” POGO said. It was only a matter of weeks before the FDA reversed its decision on migalastat.
“This guidance from the FDA marks a tremendous step forward for thousands of people living with Fabry disease in the United States,” Crowley said in a statement following the reversal. “We are moving ahead expeditiously with our NDA submission and accelerating the U.S. pathway for migalastat. Today is a seminal moment in the development of migalastat and a testament to the dedication and perseverance of the patients, physicians and employees who have worked so hard on the development of this precision medicine.”
In a statement issued this morning, Crowley said the company’s engagement with the FDA and other regulatory bodies have been focused on “the science and data we have advanced through a decade of clinical research in Fabry disease.” He said the NDA submission includes a robust data package that includes information from the two largest Fabry pivotal studies ever conducted.
Amicus engaged the FDA in multiple meetings that allowed the company to share new data on migalastat, as well as patient testimonies from Europe, where the drug, marketed as Galafold, was approved for use in 2016. Crowley said that is what enabled the company to submit its NDA this week.
“As CEO of Amicus, I am dedicated to advocating in the best interest of patients. We stand firmly behind our engagement with FDA, and remain committed to advancing migalastat through the regulatory process as quickly as possible,” Crowley said in his statement.
When President Donald Trump tapped Gottlieb to serve as FDA Commissioner it was largely seen as part of a belief that the administration wanted to reform the regulatory agency and see more drugs approved. Earlier in the year on Rare Disease Day Trump highlighted work done by Crowley at his former company Novazyme Pharmaceuticals to develop a treatment for Pompe Disease. Crowley’s daughter Megan was diagnosed with the disease at 15 months old. On that day Trump excoriated what he called the “slow and burdensome” approval process at the FDA that prevented treatments from getting into the hands of patients that could benefit.
Hileznrath told BioSpace that POGO began looking at Amicus after Crowley met with Trump prior to his being publicly acknowledged on Rare Disease Day. Hileznrath said POGO “watched with interest” as the FDA reversed course on migalastat and that prompted the organization to request related records under the Freedom of Information Act.
Since Gottlieb took over at the FDA the agency has reversed three decisions on drugs it previously rejected. In addition to Amicus the FDA reversed course on Eli Lilly’s rheumatoid arthritis drug baricitinib and TherapeuticsMD’s vaginal pain medicine TX-004HR.
Since POGO filed its report on Thursday shares of Amicus have fallen from $13.25 to $12.85 this morning.
