AMT-130 and the 75% Slowdown: What Just Changed for Huntington’s Disease—and What Hasn’t

We Have A Voice Radio dives into the AMT-130 news for Huntington’s—what this one-time, brain-delivered gene therapy is, what the reported “75% slowdown” really means, what’s next for approval, and the hard truths on access and cost.

Episode Transcript

Speaker 1 (00:16):
It's time to speak up.

Speaker 2 (00:18):
It's time to speak out.

Speaker 1 (00:20):
Welcome to We Have a Voice.

Speaker 2 (00:24):
Community discussions about Huntington's Disease.

Speaker 1 (00:27):
And Juvenile Huntington's Disease.

Speaker 2 (00:30):
Show host James Valvano, You are loved.

Speaker 3 (00:39):
Hello, and welcome to We have a Voice Radio. My
name is Kevin Jess and I'll be your host today. Tonight,
I want to talk about news that landed like a
thunderclap in the Huntington's community. A gene therapy from Unicure
called AMT one point thirty has reportedly slowed Huntington's disease

(00:59):
progress by seventy five percent over three years in people
who receive the high dose. That number seventy five percent
has been the echoing around headlines for good reason, for
a condition that has taken so much from so many families,
a result like this feels almost unreal. But let's take

(01:20):
the time to really unpack it. What the therapy actually does,
how it is given, what the data really show, what
the road to approval looks like, and yes, the hard
realities about cost and availability. First, what is AMT one
thirty well. AMT one thirty is a one time gene

(01:44):
therapy designed to lower the amount of the Huntington protein
in the brain. It uses a harmless delivery vehicle, a
virus called aa V five, to carry genetic instructions into
specific brain cells. Those instructions encode a small RNA. Think
of it like a guided message that tells the cell's

(02:08):
own machinery to silence the Huntington gene's message, so the
toxic protein gets made in much smaller amounts. This approach
is called RNA interference or gene silencing. The pyalo for
a MT one thirty is a micro RNA, often described
as mihtt. After delivery, that micro rna binds to the

(02:34):
Huntington messenger RNA and flags it for cutting, which lowers
Huntington protein production inside the cell. That's the core idea
reduced the poison at the source. Now, how is it administered?
This is not a pill, not an IV infusion. In
a clinic, a MT one thirty is delivered through stereotactic neurosurgery,

(02:58):
a precisely navigated brain procedure under MRA guid m UP
sorry MRI I guidance. Surgeons make several small burholes in
the skull and thread microcatheters deep into the striatum. That's
the KOD eight and putamen the keihabs devastated early in

(03:19):
Huntington's Through those catheters. The therapy is infused using convection
enhanced delivery. Imagine a very slow, even push that helps
fluid fluid distribute through the brain tissue. It's meticulous, hour
by hour work with real time MRI confirming where the

(03:43):
fluid is going. The technique uses specialized gear, including canulas
from Clearpoint neuro and in earlier reports, individual procedures could
take many hours. And let's move to the results that
spark the world's at tension. In a pivotal Phase one

(04:03):
two program combining US and European cohorts, Unicure reports that
people who received the high dose of a MT one
thirty showed a statistically significant seventy five percent slowing of
disease progression at thirty six months compared with a matched

(04:24):
external control group drawn from a large Huntington's Natural history database.
They measured this using the Composite Unified Huntington's Disease Rating
Scale or CUHDRS, a global score that combines movement, cognition,
and function. The company also reported significant slowing on total

(04:48):
functional capacity, a key functional endpoint, and favorable trends in
other motor and cognitive tests. Importantly, neurofilament light, a marker
of neural damage, was on m average below baseline at
three years in treated patients. That constellation of signals is
why you're seeing such strong headlines. You've also heard the

(05:09):
seventy five percent figure in mainstream coverage papers in the UK,
market columns in the United States science outlets aligning on
the same statistic from the high dose group at three years.
This isn't just a lab biomark or wiggle. It's a
clinical slowing on scales that matter to daily life. That's
why people are calling it landmark. Now for the nuances,

(05:34):
because radio should give you the whole truth. First, this
was not a classic randomized, placebo controlled phase three with
a huge number of patients. The Pivotal analysis used propensity
score matched external controls from the inroll HD database to
compare against the treated patients. That's a scientifically accepted approach

(05:58):
in rare diseases. Regulators do allow it, but it's not
the same as a large, blinded, sham controlled trial. The
company says the analysis plan was aligned with the FDA
in advance and they report p values supporting the findings,
but the sample is still small and external control designs
always invite debates about matching and hidden biases. Those are

(06:21):
real questions that FDA reviewers will dig into. Second dose matters,
the big win was in the high dose court. Lower
doses showed more modest and variable trends. That dose response
pattern actually strengthens the biological case, but it also means
the field will focus on whether the high dose can

(06:41):
be delivered consistently and safely across many centers as it
rolls out third safety and procedure burden. The company describes
a MT one thirty as generally well tolerated with a
manageable safety profile. At the three year look, many adverse
events were worth related to the surgical procedure and resolved.

(07:02):
But let's be clear, this is brain surgery with multi
hour anesthesia, precision catheter placements, and center of excellence logistics.
There's nothing casual about it. People and families will have
to weigh the risk benefit of a one time invasive
therapy against the trajectory of Huntington's So what's next? Unicure

(07:24):
says it plans a pre bla meeting with the FDA
this year and aims to submit a biologic biologic license
application in the first quarter of twenty twenty six. They
flagged the possibility of a US launch later in twenty
twenty six if approved. The program has breakthrough therapy and
RMAT designations, which can speed interactions and support expedited pathways,

(07:49):
but they do not guarantee approval. Still, between the magnitude
of the high dose effect, the support of biomarkers story,
and the desperate UNNT need, it's fair to say the
regulatory wins are finally at the communities back in a
way they haven't been for years. So will it be licensed, Well,
we're not there yet, but the signal is strong enough

(08:11):
that a twenty twenty six FDA decision is a reasonable expectation.
If the submission is accepted on that timeline, Europe and
the UK would likely follow on their own timelines, often
months to more than a year later, depending on regulators.
In any requests for confirmatory data, nothing is guaranteed, but

(08:32):
the first time, for the first time, we can talk
about a plausible path to approval of a therapy that
changes the course of Huntingon's not just its symptoms, So
who would be eligible if approved right now? The trials
focused on early manifest Huntington's people with established symptoms, but
earlier in the disease course. That's where you can most

(08:53):
clearly see a slowing signal. As always, the eventual label,
the wording of who can get it will be defined
by the FDA review, and even if the label is broad,
real world access will depend on surgical capacity, insurer decisions,
and whether hospitals build the teams needed for an MRI
guided convection enhanced delivery. Early on, expect a limited number

(09:17):
of centers with trained neurosurgical teams to handle cases. What
about availability and rollout? Even optimistic timelines imply specialized center rollouts.
Think major academic hospitals with neurosurgery, interoperative MRI and experience
with clear points don navigation and canulas. Given the intensity

(09:41):
of the procedure, initial throughput, how many patients can be
treated per center per month will likely be modest. Companies
often start with centers of excellence, train additional sites, then expand.
Let's talk about cost, because it's the elephant in the room,
especially in the United States, No official price exists for

(10:04):
AMT one thirty today, but we can triangulate from other
gene therapies. The going rate for one and done genetic
medicines has climbed into a new stratosphere. Luxterna for retinal
dystrophy lists around eight hundred and fifty thousand dollars. Z
Genzma for SMA famously launched at about two point one million.

(10:28):
Zintiglow and Skysona from Bluebird have carried two point eight
to three million dollar priced tags. Alevitis for Duschen's muscular
dystrophe lists around three point two million in the United States.
These are all intravenous or localized administrations, but AMT one
thirty adds a long, highly specialized brain surgery with MRIs

(10:51):
sweet time and an elite team. When you add hospital
costs and the scarcity of capable centers, you can make
a sober educated guest that list pricing and fully loaded
episode costs could land well north of a million dollars
and plausibly in the two to three million dollar neighborhood
in the United States. I hope I'm wrong on the
high side, but the market precedent for gene therapy suggests

(11:14):
we have to take that possibility seriously? Will insurers pay
in rare diseases with strong data and no alternatives? US
payers have more often than not found ways to cover,
sometimes with installment payments, sometimes with outcomes based contracts, but
every pair negotiates differently. Medicaid coverage varies, state state private

(11:36):
plans vary even more. For families, the practical question often becomes,
is there a designated treatment center in my region? Is
my plan contracted with them? And what does the prior
authorization process look like? Those are boring bureaucratic questions that
decide who actually gets treated? What about outside the United States?

(11:56):
In the UK and ICE evaluate it's cost effectiveness. Gene
therapies can face tough, months long appraisals in the EU,
each country negotiates. Some countries push prices down, others move slowly.
There's also the matter of neurosurgical capacity, so even after
approval in any region, access will not be uniform. Now,

(12:20):
because this is we have a voice radio, I want
to center what this means emotionally, but with clarity for
families living with Huntingdon's we have endured decades where hope
felt like a luxury, and maybe someday was all anyone
could honestly offer. The AMT one thirty data are different.
A three year high dose seventy five percent slowing on

(12:40):
a core clinical measure alongside a biomarker signal that suggests
less nerve cell damage. That's real. It doesn't erase what
people are going through today. It doesn't fix the lass
that has already happened in so many families. But it
changes the conversation from we can't alter the disease to
we might be able to slow it meaningfully. Is a
sea change. At the same time, we have to hold

(13:03):
onto cautions. The analysis relied on external controls that can
be robust when done well, and regulators know how to
read it, but it is not the gold standard randomized
comparison we all wish we had. The sample size is small,
that's the reality of early Huntington's trials. But small numbers
mean that unusual outcomes good or bad, can sway the averages.

(13:26):
More follow up will matter, and this is major brain surgery.
Even if the long term benefit is real and durable,
the upfront hurdle isn't trivial. Not everyone will be a candidate,
not everyone will feel comfortable with it, and is it
a cure. No, slowing is not reversing. The goal here
is to stretch time, to turn one year of expected

(13:47):
decline into three or four years at the same level
of function. Some outlets have used treated successfully or world changing.
I understand the emotion, but for radio let's be strict.
This is compelling evidence of disease model occasion, not a cure,
and we will need to see how durable it remains
beyond three years. And could AMT one thirty be used

(14:08):
earlier before symptoms. That's the dream to treat pre symptomatic
characters carriers and delay onset, but that requires separate studies
and risk benefit math that regulators and families will approach
very carefully because the surgical risk might oweigh might weigh
differently in someone who's not yet symptomatic. For now, the

(14:28):
data and any near term approval will be an early
manifest disease what able competition or combination therapies, while other
approaches antisense oligos in the spinal fluids, small molecules, even
new gene editing strategies are still in development. Each has
trade offs ease of delivery versus depth of target engagement,

(14:49):
frequency of dosing versus one time procedures. One positive AVAM
to T one thirty is that it targets the striatum directly,
the ground zero of early Huntington's damage. While many the
other therapies rely on diffusion from the spinal fluid or
the bloodstream. The field is not a zero sum game.
Success here could raise all boats, forcing payers and systems

(15:11):
to build neurology gene therapy infrastructure that helps future treatments
reach patients faster. Before we close, I want to address
the question I've already gotten in my inbox. How much
hope should I let myself feel? My answer is enough
to breathe easier, but not so much that you stop

(15:32):
asking hard questions. Hope with a seat belt. Today's data
are the strongest we've ever had for slowing Huntingdon's. The
regulators still need to do their job. Hospitals need to
gear up, payers need to be pushed politely or otherwise
to do the right thing, and the community needs to
keep showing up as it always has to insist that

(15:54):
a groundbreaking therapy not become a luxury available only in
a fusic ghosts the bottom line in plane language, So
what AMT one thirty. Does it delivers a gene silencing
message into key brain regions so cells make much less
hunting and protein the root cause in Huntingdon's one shot

(16:14):
designed to last. How it's given mri I guided brain
surgery with microcatheters infusing the therapy precisely into the striatum
over many hours. What the new data show in the
high dose group a seventy five percent slowing of clinical
decline at thirty six months, with supportive function and cognitive

(16:38):
signals and a brain surgery biomarker trending below baseline. Strong
but still from a small study using external controls. And
what's next. Unicure aims to file with the FDA. FDA
in early twenty twenty six. A twenty twenty six US
launch is possible if approved designations like Breakthrough and our

(17:00):
maat help speed the process. Will it be licensed? The
odds got better this week, but were not at the
finish line. Regulatory review will be rigorous. Cost and availability
no price yet. Benchmarks from other one time gene therapy
suggest seven figures are likely, and the surgical complexity points

(17:21):
to limited center capacity Early on, Advocacy will matter. I'll
end with this for years, families affected by Huntington's have
kept vigil through setbacks, trials that failed, signals that faded,
hopes that slipped away. This time, the light isn't faint.

(17:44):
It's bright. Not because someone said a magic word, but
because people living with HD volunteered for brain surgery, because
clinicians executed a technically brutal procedure again and again, and
because scientists kept fighting to prove that lower Huntington could
change the curve of this disease. If the regulatory regulators agree,

(18:06):
and if we as a society decide that life changing
therapy should be reachable, not theoretical, the next few years
could redefine what it means to get a Huntington's diagnosis.
Not the end of the story, not yet, but for once,
a chapter where time starts working for families, not against them.
This is we have a voice radio. I'm grateful you're here.

(18:30):
I'm proud of this community. I promise to keep telling
the truth as we move forward, good or bad, so
that when hope knocks, everyone knows which door to open.
And always remember you are loved.