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FDA Committee Indicates Substantial Evidence Has Not Been Provided For the Effectiveness of Carbetocin as a Treatment for PWS

While the FDA is not bound to follow the advice of its expert panels, they typically do. A final decision will be shared before the end of the year.

In a disappointing decision, a panel of independent advisers to the Food and Drug Administration has voted 12 to 1 suggesting that Levo Therapeutics has not provided substantial evidence of effectiveness for carbetocin nasal spray (LV-101) in the treatment of hyperphagia associated with Prader Willi syndrome.

Several of the committee members expressed their recognition that PWS is a devastating disorder and is in need of new treatments but indicated that their vote necessarily focused on the question the FDA asked, which is whether Levo Therapeutics had provided “substantial evidence of effectiveness”. In short, most committee members felt the current data had not met that standard.

The FDA is afforded flexibility in evaluating new treatments for life-threatening rare diseases with high unmet need, such as PWS, and has a strong history of doing so for orphan products. However, while not bound to do so, the agency typically follows the advice of its expert panels. A decision on whether to approve LV-101 will be issued by the FDA before the end of the year.

“Obviously, this is a setback for our community," says Theresa Strong, Director of Research Programs at FPWR, "but we have learned nothing from PWS if not how to persevere through rough times. Our loved ones deserve a chance for a brighter future, and we’ll continue to work to see that become a reality."

Over 100 comments were submitted to the advisory committee asking them to support an approval of LV-101 for the treatment of PWS. Comments included statements on our community’s incredible need for treatments and the impact on PWS has on the entire family. We would like to thank each and every one of our commenters for taking the time to share your stories, commitment, and passion.

We would also like to thank our community members who spoke directly to the committee regarding their experiences during the Open Public Hearing: Elisabeth Dykens, Rachael Fischer, Susan Hedstrom (FPWR), Rob Lutz, Lisa Matesevac, Kathryn McGhee, Amy McDougal, Paige Rivard (PWSA USA), Elizabeth Roof, Lauren Schwartz Roth, Sasha Tweel, and Roxanne Wolfer. The testimonies shared were moving, thought-provoking, and clearly described our community's tremendous need for new treatments for our loved ones. They included such important points as:

  • PWS is a rare, life-threatening disorder that profoundly impacts individuals with PWS and their families.
  • People with PWS live with life-threatening risks every day and are tolerant to considerable risk in exchange for moderate improvements in hyperphagia
  • The improvements that have been seen with treatment with LV-101 have been meaningful to both individuals with PWS and their families.
  • Our community wants LV-101 approved!

A recording of the webcast is available here. Community testimony begins at the 4:57:20 mark.

“We are so disappointed to see the hard work and efforts of the PWS community fall short in the eyes of the advisory committee,” said Elizabeth Roof, Senior Research Specialist at Vanderbilt University. “We feel that the study evidence was overwhelming and coupled with the heartbreaking stories of the intense, life-threatening hunger in PWS that currently has NO FDA approved treatments, we were surprised and saddened that the advisory committee did not vote in favor of this safe and effective drug.”

"We thank our investigators, the patients who enrolled in our trial, and the many PWS community members and advocates who shared their personal thoughts and experiences at today’s meeting, reflecting the significant unmet need for a treatment for PWS," says Sara Cotter, CEO of Levo Therapeutics. "While we are disappointed by the outcome of today’s vote, we appreciated the opportunity to share our data with the Advisory Committee, and we will work with the FDA as it completes its review of our application.  We continue to believe that carbetocin can provide a much-needed option for patients based on the favorable benefit/risk profile demonstrated in the clinical development program."

CARE-PWS, a phase 3 study of LV-101 (intranasal carbetocin), tested two doses of LV-101 versus placebo. The 3.2 mg dose of LV-101 provided statistically significant improvement in hyperphagia, clinical global impression of change, and anxiety and distress behaviors, in patients with PWS when compared to patients on placebo. However, improvements seen with the 9.6 mg dose of LV-101 did not reach statistical significance, and the FDA expressed concern that substantial evidence of effectiveness had not been demonstrated for the drug.

The safety of intranasal carbetocin has been supported in multiple studies and no unexpected serious adverse events were reported in the LV-101 trial. Additionally, Levo Therapeutics did not report any significant side effects associated with the chronic use of LV-101 in individuals with PWS.

While we had hoped for a different outcome from today's committee vote, FPWR remains committed to finding treatments for PWS. One thing is clear from today: we cannot rest in our efforts, we cannot pause. Our journey is not yet over. We must fight on and we hope that you will continue to fight with us.




Susan Hedstrom


Susan Hedstrom is the Executive Director for the Foundation for Prader-Willi Research. Passionate about finding treatments for PWS, Susan joined FPWR in 2009 shortly after her son, Jayden, was diagnosed with Prader-Willi Syndrome. Rather than accepting PWS as it has been defined, Susan has chosen to work with a team of pro-active and tireless individuals to accelerate PWS research in order to change the future of PWS. Inspired by her first FPWR conference and the team of researchers that were working to find answers for the syndrome, she joined the FPWR team in 2010 and led the development of the One SMALL Step walk program. Under Susan’s leadership, over $15 million has been raised for PWS related research.