Dear @lemlem ,
Any drug manufacturer can apply for a fast track designation from the FDA for a drug which has the potential to offer a significant improvement over the standard of care. The fast track approval does not signal any proven efficacy or improvement over the standard of care but signals that the FDA will prioritize the review of clinical data from trials with the agent in question. This does not speed up the time to conduct clinical trials or change the thresholds required for approval. When clinical trials of NAPs resume, we fully expect to apply for and receive this designation from the FDA for REP 2139-Mg.
It is difficult for laypersons to parse examine the real clinical data and what they actually mean versus high level statements made about overall functional cure from the actual data. This is why patients often get confused after reading these high level statements.
In the case of bepirovirsen, HBsAg loss during therapy is restricted to patients with low HBsAg at baseline and declined from ~23% at the end of therapy to ~10% 6 months after removal of bepirovirsen. While the 6 month treatment free follow-up component is part of the functional cure definition, the rapid rebound in HBsAg in most of the patients during this fairly short term follow-up tells us that the functional cure rate is very likely to be significantly less than 10%. We have not yet seen the 48 week follow-up from the phase IIB study. The currently enrolling phase III study is being entirely restricted to patients with low baseline HBsAg. Recruitment is very slow in this study because these kinds of patients represent a small minority of patients (~10%). With this kind of restricted enrollment, we will not get to see how the drug performs in the patient population overall.
Incidentally, the phase III largest trial with pegIFN (combined of not with pegIFN), showed that pegIFN+TDF has a functional cure rate of ~9% but this is regardless of baseline HBsAg. In patients with low baseline HBsAg, pegIFN functional cure rates are up to 30%. So when comparing similar clinical populations, pegIFN actually outperforms bepirovirsen. Again the problem with pegIFN is a fairly low functional cure rate with typical levels of HBsAg (~10,000 IU/mL or more) and the lack of effect against genotype D.
In the case of REP 2139-Mg+pegIFN, we have shown that the functional cure rate is 39% after one year of no therapy which increases to ~56% after 5 years of no therapy. This is regardless of baseline HBsAg or HBV genpotype. This is a qualitatively different response from any other agent in development.