One Year After the Govorestat CRL
Galactosemia Reimagined
It has been one year since the FDA issued the Complete Response Letter (CRL) for Govorestat — and somehow, the weight of that moment still sits on this community like it happened yesterday.
A year later, most families are still asking the same questions:
What happened? Why hasn’t anything changed? And what does this mean for our children?
So today, I want to do something the system hasn’t done for us:
tell the truth plainly.
A Quick Reminder: What the CRL Actually Was
A CRL is not a final rejection.
It is not an announcement that a drug “failed.”
It is not a verdict about safety or harm.
A CRL is simply the FDA saying:
“We cannot approve this right now, based on how we interpreted the data.”
But interpretation is the key word here — because interpretation is exactly where the system breaks down for ultra-rare disease.
What We’ve Learned in the Last Year
1. The science wasn’t the problem. The system was.
In the year since the CRL, we’ve had:
more real-world patient experience
more long-term extension data
more consistency across outcomes
more proof that the improvements families observed were real and repeatable
Nothing about the biology of Galactosemia has changed.
Nothing about the mechanism of action has changed.
Nothing about the unmet need has changed.
What has changed is our clarity.
We understand even more deeply now that Galactosemia doesn’t fit the FDA’s rulebook — at all.
2. The statistical framework for ultra-rare disease is still broken
This past year has shown, once again, what the CRL revealed:
You cannot use big-population math to judge a micro-population disease.
Galactosemia trials will never have:
hundreds of patients
identical phenotypes
clean, linear data
traditional p-values that behave the way FDA wants them to
Why?
Because those conditions don’t exist in the real world of ultra-rare disease.
The FDA’s statistical expectations remain designed for cholesterol drugs, asthma trials, and diabetes studies — not for diseases with global trial populations smaller than a single classroom.
A year later, that mismatch is still the problem.
3. FDA’s existing flexibility pathways still weren’t used — even though they applied
In the past 12 months, we’ve confirmed what many of us said the day the CRL was issued:
The FDA already had the legal authority to approve Govorestat under:
FDASIA §901 (Benefit–Risk for serious diseases)
§112 (single adequate study)
21 CFR 314 Subpart H (Accelerated Approval via surrogate endpoints)
21st Century Cures Act (Real-World Evidence)
FDARA 2017 (Patient Experience Evidence)
These aren’t loopholes.
They are the tools Congress created specifically for situations like ours.
And a year later, the elephant in the room is this:
Those tools are still not being applied in ultra-rare disease. Its a very gray area at FDA and they need more support to utilize these tools.
What This Has Shown Us About Galactosemia
1. Our children continue to live with a disease that medicine still pretends is “managed.”
Nothing about the last year changed the truth families already knew:
diet doesn’t stop tremors
diet doesn’t prevent cognitive decline
diet doesn’t heal white matter injury
diet doesn’t fix ovarian failure
diet doesn’t reverse metabolic stress
diet doesn’t stop stomach issues
diet doesn’t eliminate seizures
The CRL didn’t expose anything new about Govorestat.
It exposed everything old about the system.
2. Parents’ observations continue to be treated as “soft data” — even though they are the earliest and most accurate signals.
Families and patients are still the first to see but have been gaslit to the ground on their opinions.
the “brain fog weeks” before a growth spurt
the subtle tremors
the processing delays
the irritability that precedes metabolic overload
the difference after a dose adjustment
One year later, the FDA still doesn’t have a mechanism that reflects how ultra-rare disease actually behaves in the real world.
That’s not a science problem.
That’s a policy problem.
3. The lived experience is still ahead of the system — by years
And the gap between what families know and what the FDA recognizes is growing, not shrinking.
In the last year, science moved forward:
CRISPR accelerated.
N-of-1 therapy frameworks expanded.
AI protein design changed everything.
But regulation did not move with it.
Where We Stand Today
This is the part I want every Galactosemia family to hear:
We are not back at square one.
We are not powerless.
The story didn’t end with the CRL.
In the last year:
new leadership emerged at the FDA
the Rare Disease Innovation Hub expanded but still need authority to act in the gray
Congressional offices became more involved
the ultra-rare development crisis became undeniable
your advocacy got louder, more organized, and more respected
evidence grew, not shrank
The CRL was a system failure — not a scientific one.
But it became the spark for everything we are building now.
Why This One-Year Mark Matters
Not because the FDA made a decision.
But because the decision forced the truth into the open:
Galactosemia is not “diet-controlled.”
It is a chronic, untreated, progressive metabolic disorder.
And it deserves:
its own pathway
its own endpoints
its own statistical tools
its own urgency
This moment is where the system gets reimagined — because it has to.
One Year Later, What Comes Next
Everything we’re doing now, the policy work, the science, the biomarker innovation, the regulatory pressure, is part of a much bigger shift:
We are building the pathway that should have existed before the CRL.
We are rewriting what the FDA should have done the first time.
We are refusing to let another generation go untreated.
And that is exactly what Galactosemia Reimagined is here for.
Because one year later, we are not defeated.
We are clearer.
We are louder.
We are backed by more science.
We are building more evidence.
We are not waiting for the system to catch up —
we are dragging it forward.
This is not the anniversary of a rejection.
This is the anniversary of a turning point.
And we are just beginning.
Disclaimer:
This blog reflects my personal experience as a caregiver and RN. It is for education and advocacy only and is not medical advice. Always consult your healthcare team for medical decisions.
