Birinapant has not failed in the sense that it was tested and did not show a meaningful effect.
But it appears that the first trial was rushed into possibly with doses too high and without any protective measures to prevent the facialis nerve paralysis side effect.
the current anouncement of an India trial with very small initial doses and as a monotherapy without pretreatment is likely suboptimally designed as well.
Tetralogic is overall in bad shape, the stock is 18 cents now and the majority of its staff was fired due to its financial situation. The reason for this is the lack of birinapant efficacy in the major cancer trial.
Nevertheless these are just major misfortunes, a streak of bad luck. We know that birinapant can have dramatic effects on human hbv if used properly and paradoxically if the palsy can be shielded against, does not seem to have significant side effects.
The problem is that it might never see proper development towards an approved drug for hepatitis b.
I can't but agree with stephen's comment. We are most likely at least few years from a cure
The short answer to your question, in my opinion, is Yes.
In 2009, some of us believed a cure had been discovered with the release of small clinical trial results of REP9AC. Today, we are more or less at the same point. The big disappointments in the last few years were:
1 Failure of GS9620 (TLR7 agonist)
2 Failure of GS4772 (therapeutic vaccine)
3 Failure of Birinapant
(a major lesson learned is that there is a big gap between animal models and humans)
4 Failure of GLS4 (capsid inhibitor)
5 Failure of YIC (therapeutic vaccine)
6 Low rates of success of combination therapy involving oral antivirals and PegIFN.
The major changes that indirectly affect drugs development for HBV are:
1 Cures for HCV, so attention shifting to finding a cure for HBV.
2 Immunotherapies for cancers (checkpoint inhibitors, CART, etc). Some of these can be applied to HBV, but the infected liver is not a tumor, so safety requirement is much higher.
3 Revival of RNAi technology - suddenly drug companies discovered that the liver is a easier target to deliver RNAi to, and reduction of HBV viral antigens in the serum is an important part of a cure by by own immune system (no-one acknowledged that this was indicated years ago by REP9AC).
4 General advances in basic science such as gene-editing tools like CRISPR.
There seems to be general agreement that a HBV cure will be a combination approach (reduction of viral load, reduction of viral antigens, revival of "exhausted" immune functions) or a direct assault on cccDNA in the infected liver cell nucleus.
As one scientist remarked: the excitement is palpable. But we are still a long way from a cure.
Just my personal opinions.
thanks!
any link for the cuban vaccine?
best regards
With regards to cure the Replicor made advancements and is now in phase II clinical trials, showing it can cure hep b carriers with 50% of higher chance. With that said it will take, IMO, at least 4 years to start being available on the market, probably even longer than 4 years...
Other than that we have TAF (new version of Tenofovir which is better for kidneys) coming out very soon (in few months in USA and Europe), and will probably represent the best medicine that will be available on the market for the treatment of Hep B.
There is also hope that Cuban Vaccine might provide real beneficial effects regarding treatment and that it could be out on the market in near future.