When benefit-risk assessment becomes the focus, a new round of supply-side reform of innovative drugs begins

On July 2 last year, the Food and Drug Administration issued the "Clinical Value-oriented Guidelines for Clinical Research and Development of Anti-tumor Drugs", which gave those pharmaceutical companies that are willing to roll up a head start
.

The meaning of the document is simple and clear: curb the momentum of following the trend and avoid repeated consumption
of clinical resources.
After the release of the document, a top-down supply-side reform continued
.

As a result, many players who implement the Me too strategy have their stock prices falling endlessly
in the secondary market.

The good point is that after more than a year of baptism, more and more domestic pharmaceutical companies have begun to follow the "clinical value"-oriented research and development ideas
.

However, the changes are not over
.

On November 8, 2022, CDE issued the Technical Guidelines for Risk Assessment of New Drug Benefits (Draft for Comments) (hereinafter referred to as the Draft Comments), conveying clearer opinions:

Benefit-risk becomes the key
to the marketing review of innovative drugs.

This may indicate that a new round of supply-side reform in the innovative drug industry has begun
.

       / 01 /

Benefits – Risk becomes key to IPO review

From PD-1, CAR-T, CD-47.
.
.
There is no target that can avoid the fate
of involution in China.
This is counterintuitive and unsustainable
.

From the perspective of policy, the meaning of the NMPA is very clear: to clear unnecessary production capacity
.
On November 8, CDE released the Draft Opinion, which aims to do just that
.

According to the Draft Opinion, the marketing application of innovative drugs: the benefits of drugs – risk assessment is a key process in regulatory decision-making, which ultimately determines whether it is approved
.

What does that mean? It can be divided into two dimensions
.

A drug
used to treat serious diseases and have unmet clinical needs.
For such drugs, reviews may accept greater uncertainty of benefit or risk;

Second, drugs used to treat non-serious diseases, when other treatment options are available, it is difficult to accept the same large uncertainty
of benefit or risk.

The meaning of the Draft Opinions is simple and clear, and innovative drugs applying for marketing must prove that the benefits outweigh the risks
.

This means that it will be increasingly
difficult to market Metoo drugs with mediocre efficacy, or Me-worse drugs with worse efficacy.

So, how do you prove that you're not Me worse?

The Draft Opinions also provide an answer: weighing "benefits" and "risks" is mainly a comparison of favorable and negative effects, and explains how it is affected by uncertainty
.

Decisions are often made on the basis of large amounts of complex data about the expected benefits and potential risks to patients who may actually use the drug
.

Simply put, pharmaceutical companies need solid data to prove that their benefits and risks are better
than existing drugs.

Since the assessment of drug benefits and risks is the result of comparisons of different dimensions and different indicators, it is difficult to draw conclusions
directly.

Therefore, CDE has carefully developed a benefit-risk assessment framework to provide key issues, evidence and uncertainty information in benefit-risk assessment to clearly reflect the benefit-risk assessment process
of drug regulatory decisions.

In other words, pharmaceutical companies can check whether they meet the requirements according to the
CDE process.

In the past, pharmaceutical companies may know that their products are a me worse product, but under the influence of capital, they may also want to rush up to try it
.

But now CDE has made the requirements clear, intended to dissuade some indiscriminate people, so that pharmaceutical companies are committed to developing drugs
with better effects in the clinical research and development stage.

       / 02 /

Clear judging criteria

Of course, for more pharmaceutical companies, it is bound to prove that their products are me better
.

In fact, for a long time, there was no clear dividing line
between domestic Me worse, Me too, and Me better drugs.

Individual domestic innovative drugs may not even conduct head-to-head clinical trials, but rely on a single-arm clinical data, a more likely to reach the clinical endpoint, to claim that their developed drugs are Me better drugs or even Best in class drugs
.

After the landing of the Draft Opinions, these ambiguous middle ground will no longer exist, and many provisions in the Draft Opinions have given the way
for Me better drugs to prove their effects.

For example, the Draft Opinions states:

To select measurable subjective data as clinical endpoints, if clinical surrogate endpoints are selected, their relationship to clinical endpoints should be described, as well as the ability and basis
for surrogate endpoints to predict clinical benefit.

This also means that in the past, some pharmaceutical companies relied on ORR endpoints to replace OS to muddle through, and the practice of boasting about the efficacy of drugs is likely to not work
.

For example, the Draft Opinions mention that when using a positive control group, it is necessary to ensure that the drug does not have safety problems compared with the drugs that have already been available, or that the effect is better
than the existing therapy.

In other words, if a pharmaceutical company wants to conduct clinical trials for an indication, it needs to conduct head-to-head trials with drugs that have been approved for marketing in that indication to prove that they are better
.

All in all, CDE has given operating rules in terms of proving the effect, and pharmaceutical companies need to do it according to the rules if they want to show that they are stronger, and they have achieved it in order to be called me better drugs and get the opportunity
to be approved for marketing.

In the future, if the new policies of the Draft Opinions are strictly implemented, then presumably many innovative drugs that claim to be me better will be exposed
.

       / 03 /

Promote the benign development of the innovative drug industry

The continuous advancement of supply-side reform will inevitably have more advantages than disadvantages
for the entire pharmaceutical industry.

We need drugs
that work better and target unmet clinical needs.
However, under the influence of capital, there is a low level of duplication in the research and development of innovative drugs, which is an extreme waste of clinical resources
.

This is also why the field of domestic innovative drugs is large but not strong
.

As early as 2020, the domestic drug review center accepted as many as 1,062 applications for the registration of Class 1 innovative drugs
.
This number is a number that even the FDA is ashamed of
.
During the same period, FDA received 861 registration applications
.

But today, there are very few domestic innovative drugs that have really completed going to sea
.

In this context, it is not difficult to understand the significance of the draft opinions: through the tightening of drug approval and listing, good money drives out bad money, frees up the market for real innovative drugs, and also promotes the determination
of enterprises to move up.

From the "Guidelines for Clinical Research and Development of Clinical Value-oriented Antitumor Drugs" issued by CDE on July 2 last year to the issuance of today's Draft Opinions, it is not difficult to find:

In recent years, CDE's drug review policy has been continuously tightened and standards have been continuously improved, further aligning
with FDA guidelines.

Obviously, the regulatory system of the domestic innovative drug market is becoming more and more mature
.
This will continue to deteriorate for players who are accustomed to rubbing hot spots and do not have a real spirit of innovation;

But on the contrary, for those players who are committed to solving unmet clinical needs and developing truly innovative drugs, now is the best time
.

As Dickens's A Tale of Two Cities says, this is the best of times, this is the worst of times
.