FDA will drop two study requirement for new drug approvals, aiming to speed drugs

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This is interesting, thanks @Nawab.

Iā€™m not sure that people from the FDA would be able to comment publicly on the effects of this, but can any @ScienceExperts or @HealthExperts suggest any impact of this change on Hep B drugs in the development pipeline?

TT

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Hi all,

I was quite interested in this decision. Andrew Vaillant @availlant would likely know more as he works in clinical research.

My initial impression is of careful optimism. Expecting 2 large clinical trials adds a great deal of time and cost to the drug development process, and the FDA in my opinion has been excessively conservative in its expectations for new HBV therapeutics. There is a risk that unanticipated subtle design flaws in a trial could increase risk with a drug approved under this more streamlined approach. However, clinical trial design is a well understood field and the FDA will still go over all the data with a fine-toothed comb, and they would have no hesitation to ask for another trial if they were worried. Also, this approach has been used successfully for years with other indications. So I think the benefits from accelerating the approval processes likely substantially outweigh the very small added risk.

John.

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Dear all,

I think John has hit all the points correctly here.

HBV drug developers will still be required to perform phase IA and phase IB trials to gather data on safety, pharmacokinetics and initial human efficacy to support phase IIA studies. Phase IIA studies gather the safety and efficacy of defined doses of drug in infected patients, typically 5-15 patients per treatment group. It may be that approval could them come from significantly large enough phase IIB trials (~400 patients) were the new drug is compared to the standard of care.

For HBV, since the only approvable endpoint is functional cure, this would normally be pegIFN but since this drug has a poor efficacy (<6%) which is largely restricted to unicorn patients (see below), this may not be required.

For HDV this will be bulevritide.

However, there is a HBV specific complication here and this is baseline HBsAg in patients. The well recognized baseline threshold of 1000 mIU/mL HBsAg defines two distinct populations:

  1. <= 1000 are unicorn patients which represent ~5% of patients globally and are much more responsive to immunotherapy
  2. >1000 (typically in the range of 3000-125000 IU/mL) represent the other 95% of patients where functional cure is not achieved by NUCs or pegIFN

We have known for decades that results in the first patient population do not translate to results in the second population.

So in the case of phase IIA, phase IIB and phase III studies which are specifically enriched in unicorn patients (these represent virtually all HBV studies currently being conducted), it is hard to predict how regulators will respond to efficacy data derived from this niche patient population. It may be that for overall patient approval, additional large studies will be required which specifically exclude unicorn patients.

@availlant

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Thank you for this clear explanation. Any news from replicator yet? :blush:

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Dear @Smart55 ,

Our latest clinical data can be found here:

https://www.journal-of-hepatology.eu/article/S0168-8278(25)02612-1/abstract

We are working on starting trials soon to begin the last steps required to bring NAPs to the market.

@availlant

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I am happy to hear this. Well done and my best wishes to you and your team.

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