The FDA "changes its face" again, how to survive in contradictions

preface

preface

On September 8, 2022, the FDA convened a second expert advisory board for Amylyx's new "ALS" (ALS) treatment, and experts voted 7:2 to support the approval of the therapy, in stark contrast

Are the results of the two meetings really a "big reversal"? Not really

"Good location to follow"

The onset is insidious and not easily detected in the early stages

Progression is faster after onset, with the vast majority of patients usually living only 3 to 5 years after diagnosis

And most importantly, there is currently no medication to cure the disease

Based on this "gray background", the FDA expert advisory committee from the first 6:4 to the second 7:2 "big reversal" has become "traceable", because the editor found several "contradictions".

Because Xiaobian found several "contradiction points".

The first is that the convening of the two expert advisory committees is somewhat "forced"

The "contradiction" between the functions of regulators and clinical needs

As early as the first meeting, the expert advisory committee spent nearly 2 hours discussing the comments made by the public, and it is not difficult to see how much pressure the public opinion has brought to the FDA, although it finally opposed Amylyx's application 6:4, but this decision also swept the FDA into a wave of criticism

Although it eventually rejected Amylyx's application 6:4, the decision also drew the FDA into a wave of criticism

"The FDA is in a challenging position to make subsequent regulatory decisions

At the second meeting, both the proponents and the opposing parties had their own opinions

Supporters

Supporters

From a clinical perspective: Liana Apostolova, a professor at Indiana University School of Medicine, said she doesn't want to let go of any drug

In the face of such a poor prognosis for ALS, I don't want to let go of any medication that

Objector

Objector

Caleb Alexander, a professor at johns Hopkins University's Downberg School of Public Health, may have considered the bad cases after the failure of the Covis Pharma confirmatory trial some time ago, and said that if the Phase III Phoenix trial of AXS0035 fails, what should be done?

Indicates what if the Phase III Phoenix trial of the AXS0035 fails?

Only the FDA is in an "awkward" situation of "ambiguity

Only the FDA is in an "awkward" situation of "ambiguity

This indirectly contributes to the 7:2 advantage

In fact, in the history of the FDA, there have been many similar cases (regulatory agency functions are "contradictory" to clinical needs), such as last year's discussion
about Biogen Alzheimer's disease drug Aduhelm.
This reminds me of Dr.
Wang Yaning, a former FDA top scientist, who introduced the functions of the FDA Expert Advisory Committee when he visited the pharmacy era live broadcast room: each expert is required to make a voting decision
based on the information at hand and not affected by other information.

Each expert is required to make a voting decision
based on the information at hand, independent of other information.

Recommended reading: After reading dozens of materials, Dr.
Wang Yaning, a former TOP FDA scientist, smoothed out this matter (with speech video + PPT)

Recommended Reading:

Settle down in "contradictions"

Settle down in "contradictions"

As Dr.
Wang Yaning said, the obligations and guidelines of being a regulatory body are to be responsible to the patient community and to objective facts
.

But we also see that everything has a multi-faceted, peculiarity, and as a regulator, we can only maintain the relative balance
of the balance from an objective standpoint.
So the FDA's treatment of Amylyx may become a "weather vane" for dealing with other rare neurodegenerative diseases, and what adjustments will be made by heavy pharmaceutical companies in terms of project establishment?

So the FDA's treatment of Amylyx may become a "weather vane" for dealing with other rare neurodegenerative diseases, and what adjustments will be made by heavy pharmaceutical companies in terms of project establishment?

To review Amylyx's approach: Klee said at the second meeting that if the treatment does not benefit the patient, or the data shows that it is not beneficial to the patient, he promised to withdraw the new treatment AMX0035, or work with regulators and doctors to ensure that an appropriate resolution
is made.

Recall Amylyx's approach to promising to reverse the new treatment, AMX0035

In the only two negative votes, Caleb Alexander, a professor at the Johns Hopkins Bloomberg School of Public Health, pointed to a situation that could occur — that the drug would be difficult to withdraw from the market
despite the failure of the Phoenix trial.
But there are not many pharmaceutical companies that dare to make this commitment, and it can be seen that -

Amylyx takes the paradox of "unmet clinical needs" as a basis for "the broadest flexibility
.
" And the patient as the main starting point, which coincides with the original intention of the FDA, the end point is for the patient
.
This is the foundation of destiny
.

Amylyx takes the paradox of "unmet clinical needs" as a basis for "the broadest flexibility
.
" And the patient as the main starting point, which coincides with the original intention of the FDA, the end point is for the patient
.
This is the foundation of destiny
.

Industry dynamics in the ALS field

Industry dynamics in the ALS field

At present, there are four drugs approved for marketing in the world with the indication of ALS, of which 2 are EDARAVONE and Riluzole
approved by the FDA.

Despite the difficulties in research and development in the field of ALS, at present, about 67 drugs around the world have entered the clinical stage (excluding traditional Chinese medicine), of which The faster Progress to Tofersen is applying for listing at the FDA and Alsitek is applying for listing
on the EMA.
9 drugs have entered clinical phase 3, 2 drugs have entered clinical phase 2/3, 25 drugs have entered clinical phase 2, 6 drugs have entered clinical phase 1/2, and the rest are clinical phase
1.

From the above chart, we can see that the drug research and development in the field of ALS has great differentiation, and the types of drugs are very rich, including small molecule drugs, biological drugs, stem cell therapy, cell therapy, gene therapy, antisense oligonucleotides, monoclonal antibodies, synthetic polypeptides, chemical drugs, etc
.

epilogue

epilogue

Contradictions are given by people, and only by highlighting "contradictions" can we better discover problems and solve problems
.
As for the results of Amylyx's Phoenix experiment, success is of course a joy for everyone, but will Amylyx be able to deliver on its promise after failure? The medicine age is in constant attention.
.
.
It is difficult to pass the pass, and it is difficult to achieve
everything.
The medicine age and the king are encouraged
.

Resources:

Resources:

1.
Amylyx amyotrophic lateral sclerosis treatment will be approved for a second time on a specialist meeting, and there still seems to be a lack of sufficient data to support approval

1.
Amylyx amyotrophic lateral sclerosis treatment will be approved for a second time on a specialist meeting, and there still seems to be a lack of sufficient data to support approval

2.
AlS therapeutic drugs will be voted for approval by experts, and subsequent clinical trials will be voluntarily revoked if they are not successful

2.
AlS therapeutic drugs will be voted for approval by experts, and subsequent clinical trials will be voluntarily revoked if they are not successful

3.
6:4 Against! After a 7 and a half hour meeting, can the FDA withstand the pressure of the public this time?

3.
6:4 Against! After a 7 and a half hour meeting, can the FDA withstand the pressure of the public this time?

4.
Adcomm votes 7-2 in favor of Amylyx’s ALS drug on second take.
But first the co-CEOs had to make a pledge – Endpoints News (endpts.
com)

4.
Adcomm votes 7-2 in favor of Amylyx’s ALS drug on second take.
But first the co-CEOs had to make a pledge – Endpoints News (endpts.
com)

5.
Wisdom Bud official website

5.
Wisdom Bud official website

6.
Other public information

6.
Other public information