TRICALS statement on Tofersen

[Nikki J]

This is from a group of leading European ALS experts advocating for tofersen in their countries. Tofersen’s ADCOMM is later this month hopefully leading to a recommendation for approval in the US. As noted in the statement the failure to reach end points in the 6 months trial is countered by evidence of biological effect during that period followed by clinical improvements during the EAP. Note : tofersen is for SOD1 only. SOD1 is a FALS mutation

TRICALS consensus statement on Tofersen

www.tricals.org

 

[lgelb]

The advisory committee meeting is scheduled for March 22 and will be available for live streaming.

Background materials will be posted on FDA 2d before or at the time of the meeting.

 

[Nikki J]

A number of people from the SOD1 community have applied to speak at the ADCOMM including trial participants. I expect the testimony to be powerful

 

[Nikki J]

The ADCOMM is tomorrow https://l.facebook.com/l.php?u=http...3_V1gHjXWqYNvDa3Req91GC4paTkcwIt6fCM1826bdlE1

since tofersen did not meet its primary endpoint in the six month trial part of the argument for approval is based on nfl as a surrogate endpoint which has implications for trials in other forms of ALS so this is important for all of us

Biogen also has data from the ole showing clinical benefit. clinical benefit took longer to manifest than the nfl drop

 

[Nikki J]

They voted yes on one question involving nfl which may be a vote for accelerated approval ( unclear)but the second question which was essentially asking about full approval was a no 5-3 with one abstention. . However especially after aduhelm accelerated approval would be a big mess. Very disappointing

 

[Nikki J]

FDA AdComm on Tofersen Supports NfL as Surrogate End Point of Clinical Benefit, But Is It Enough for Approval?

The committee all agreed that tofersen presents a favorable risk-benefit profile in this particularly challenging patient population.

www.neurologylive.com

 

[Nikki J]

Biogen statement

Biogen Provides Update on FDA Advisory Committee Meeting on Tofersen for SOD1-ALS

SOD1-ALS is a rare genetic form of the disease affecting approximately 330 people in the United States...

www.globenewswire.com

 

[Nikki J]

This is a good analysis of what happened

FDA advisors unanimously recommend accelerated approval for Biogen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment. By a 9-0 vote, members of

endpts.com

 

[Buglaw]

I realize full approval is better, but given that the original study failed (likely due to study design not because the drug is ineffective) is conditional approval with full approval to follow a 1 year study (or whatever) an unreasonable decision?

I kind of get where they are coming from that it should have a longer placebo controlled study that backs up the OLE data.

 

[Nikki J]

I don’t think anyone expects another study with PALS. They are continuing to collect data from the ole and they are hoping for more data from the ATLAS carrier study. The problem is that sod1 is rare. It took a long time enroll especially the fast progression phase 3 cohort. And who is going to sign up for a placebo trial? No one in the US and we don’t know yet what the EU is doing.

this is utterly unlike relyvrio that had the EU for their confirmatory trial because they had already insisted on a phase 3 and they have a much greater number of PALS than a sod1 limited population.

my concern is insurance coverage - especially after the aduhelm debacle. the ADCOMM was put in a tough place. They were uncomfortable with the wording of the question and a substitute wording was offered but ultimately it came down to something most of them couldn’t vote for. I think if the direct question had been asked full approval might have been recommended as I think at least a couple might have wanted it.
I hope it works out and people can continue to get tofersen

the FDA criticized the trial design and someone even implied biogen lied when they said the trial was designed before they knew enough about sod1 and nfl but it is absolutely true. I also don’t think people realized how long it takes to see clinical effect because we haven’t had a drug that was followed for this long that actually had some people improve.

 

[Buglaw]

i mean, if insurance doesn’t cover it, people will sign up for Another study.

I fully agree the OLE data is very persuasive, but it isn’t placebo controlled. I think the adcom was in a hard place given the issues with trial design. I just don’t think it was a terrible decision.

 

[Nikki J]

Fortunately ( from my perspective) it doesn’t seem like a placebo trial for symptomatic sod1 is going to be required.

I think I have a different view because I have been following the trial from the start. . The phase 1 ole required a four month no drug wash out after the placebo phase. There were people who were pretty stable for the six month trial period who crashed during the wash out phase and died then or during early ole.Being in a placebo arm for someone with an aggressive variant ( the most common type in the US) especially for a year seems like a death sentence as those people usually die within 18 months of onset

I hope they get good data from ATLAS

 

[Buglaw]

I mean, als is a death sentence for everyone. If the treatments were a reasonable $ amount I think the calculus would be different. But, given the rarity of it and how effective it appears it might be, I assume Biogen will be charging multiples of the Relyvrio/Radicava pricing. The fda signing off fully on what will be an outrageously expensive treatment should come with certainty that it will work, imo. We live in a world of limited resources and if we spend $s here we can’t spend them elsewhere.

To be clear, I’m very very high on Tofersen. It seems to be by far the most hopeful and promising als drug. If it continues to perform as it appears it will (people staying stable or even improving over longer periods of time) or delays or even prevents onset, it’s clearly going to get full approval. I also think Biogen is entitled to the outrageous $ it will get from the drug. But, conditional approval seems appropriate to me given it failed its trial.

 

[Nikki J]

I think there is a likelihood it isn’t a death sentence if you are sod1 and get tofersen early. that is what we are seeing. There are people stable for five years even in the ole. Re price the sma aso is 375k a year I think. A lot of money and more than radicava and relyvrio but tofersen does more and also is a much more complicated drug- new technology and developed specifically for sod1 with no other application for this particular drug. Not true of the other two. Radicava was repurposed. Relyvrio combined two existing substances.

as long as conditional approval allows people to get the drug I am happy.

 

[Nikki J]

NEALS had a good webinar on tofersen today.

NEALS Webinar: An Update on Tofersen | NEALS

neals.org