The best way to seek to participate in any clinical trial is to check regularly on https://clinicaltrials.gov for trials involving drugs your are interested in. These listings will provide the locations of trial sites where patients are being recruited for these trials. You can then try to see if you can get access to be recruited into the trial by contacting these trial sites.
Like all agents in development for HBV, trial participation will require 48 weeks of treatment where you will be required to visit the hospital regularly for 48 weeks (in the case of NAPs this would be once each week). This will be followed by less frequent visits after treatment is completed to monitor your progress in the absence of therapy, most likely for three years.
You can search REP 2139-Mg on the website above to get a feel for enrollment criteria we have used in our previous clinical trials.
Dear @availlant, I recently came across intriguing results from Replicor, revealing a notable increase in its functional cure rate, rising from 39% to 56%. This update is based on the latest clinical data presented at the 2023 Global Hepatitis Summit held in Paris, France, during three oral sessions from April 24th to 28th. is this correct ???
Yes these results are correct. These results (and increase in functional cure rate) are during very long term follow-up in the absence of therapy for 5.3 years.
While we are preparing for our next phase II trial, we have been deploying REP 2139-Mg in compassionate use for treating patients with chronic HBV / HDV infection who have very advanced liver disease and have failed all other available treatment options.
@availlant thank you for your quick and clear response.
since the compassionate program is only for patients who filed to respond e with other antiviral, I was following up for the next phase II trial in Europe but I have not seen any open registration. is still not yet started or it is closed https://www.clinicaltrials.gov/.
Dear @ Availlant
thanks you for your quick response.
thatās great news! the results are promising! with phase 2 in preparation, and Iām sure there will be a Phase 3. How long and I know itās hard to predict, would it be before REP 2139-Mg will be ready for patients?
Thanks you
Gregory
Even when trials are closed for recruitment, they can still be located on clinicaltrials.gov.
You are correct, there is not yet an open entry for the next phase IIA study in EU/US. Recruitment has not yet started for this trial.
Regarding timing, again it is very difficult to predict when approval of REP 2139-Mg will happen (of course we are rushing to get this done as soon as possible).
One example to keep in mind is that Bulevirtide was approved for use against HDV in the EU with only phase IIB data and the phase III was/is being done at the same as the drug is being sold.
When are the clinical trials likely in India ?
As you know that India and China has the highest number of HBV patients across the globe.
My request to you is to start trials in India in major cities. We have fabulous medical infrastructure at major cities to commence and manage these trials.
Unfortunately, I cannot reply to these kinds of questions (although they are certainly understandable). I can only advise to keep checking clinicaltrials.gov.
doctor @availlant , if Iām not going to abuse it, can you clear my doubts?
I am very excited about researching REP-2139mg and I have a question about how the medicine works. I remember you saying that bulevirtide could not obtain better results due to the way it worksā¦ in this sense, REP-2139mg, if put into continuous use, can reach patients who at first were not reached with effective healing of the medicine? Does the operation of REP-2139mg allow for this greater scope?
REP 2139-Mg has been demonstrated to be effective against HDV infection both in patients who have not received any previous antiviral therapy and also in patients who have failed to respond to pegIFN, bulevirtide or lonafarnib. In both of these scenarios, REP 2139-Mg is still the only medicine in development or approved with can achieve HDV cure in the majority of patients treated. It is expected that REP 2139-Mg will be able to achieve HDV cure at high rates in all patients, regardless of HDV genotype or prior treatment exposure.
Doctor @availlant . You told us that there is currently no medicine capable of directly attacking ccc dna hbv. I ask you if scientists have not seen any type of approach capable of doing the service or are there theories that have not been tested? Thank you
Unfortunately, there is no data yet demonstrating an approach that can target cccDNA which promises to be effective against human HBV infection. This is for two reasons:
Tissue culture and animal models do not replicate important parts of HBV biology which are present in human HBV infection (the most important of these being an ability to rapidly change genetically in response to drugs). This is why all recent drugs under development for HBV have failed to achieve functional cure in the clinic after demonstrating clear activity in these model systems.
cccDNA is more correctly thought of as a āminichromosomeā because it is decorated with the same proteins that are found in normal chromosomes. This gives cccDNA similar structure and behaviors as normal chromosomal DNA. This makes it extremely hard to effect the functioning of cccDNA without also effecting the functioning of normal chromosomes. This also makes is possible for cccDNA to hide in an inactive (condensed) state where it is virtually unrecognizable. We know that cccDNA can remain inactive in patients for decades before reactivating (typically when strong immunosuppresive agents are used for other reasons).
The good news is that functional cure CAN be achieved (75-80% of people with acute HBV naturally resolve their infection into functional cure). With functional cure, people lead long, happy productive lives and can have healthy families, all in the absence of therapy.
I apologize for repeatedly asking seemingly simple questions. Iāve come across information about Bepirovirsen, which received a fast-track designation from the FDA now. However, in its phase 2 trial, only a 10% functional cure rate was achieved, while Rep2139 achieved a cure rate exceeding 50%. Correct me if Iām wrong, but isnāt Bepirovirsen similar to Interferon by its functional cure efficiency? Iām curious about the rationale behind the fast-track designation given the disparity in efficacy. Could there be a better outcome? Please.
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.
