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Setbacks in HCV Drug Development Highlight Uncertainties in Treat or Wait Decisions

Setbacks in HCV Drug Development Highlight Uncertainties in Treat or Wait Decisions
Graham R. Foster FRCP, PhD - 10/22/2012 More from this author

HCV Trial Setbacks
I first sensed trouble in April 2012 when it was announced that trials of alisporivir were being suspended. Over 1800 patients had received this cyclophilin antagonist, with impressive virologic responses (Capsule Summary). A phase III trial was moving forward, and I was surprised to learn that a patient receiving alisporivir had died of pancreatitis. The US Food and Drug Administration noted a possible association of pancreatitis with alisporivir and instituted a “clinical hold.” A full evaluation of the alisporivir data set is now under way, and we wait to see whether any possible risks can be managed and whether it is safe to resume testing. Worse news followed in August when unexpected cardiac toxicity was seen with BMS-986094, a nucleotide analogue polymerase inhibitor, leading to the death of a patient and suspension of clinical trials. This nucleotide was just one of a molecular family, and concerns that cardiotoxicity may be a class effect led to studies with related drugs (such as a compound in phase IIb development, IDX184) being placed on full or partial clinical hold. The suspension of this drug family leaves only 1 nucleotide at an advanced stage of development (sofosbuvir, previously known as GS-7977), and I am now crossing
my fingers and hoping that its current impressive safety record continues. The failure of drugs in late-
stage clinical trials has reminded me that unexpected safety concerns are common, and despite the best
efforts of companies and regulators, clinical trials remain challenging.

PART 1
9 Responses
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Avatar universal
Hep C treatment with minimal side effects causes death!"

Now thats a good one Hector...:)
Helpful - 0
446474 tn?1446347682
Thanks cando!

Yeah I hope our Sofobuvir doesn't blow up on us. I can see the headline now... Hep C treatment with minimal side effects causes death!"
ouch!!!
Now that could ruin my whole day! haha

Hector
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1815939 tn?1377991799
Good article, Can-do.

My sentiments exactly.
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Avatar universal
Lets just hope when we see large trials with these drugs instead of just a handful of people, that the same thing that happened with the other two drugs don't repeat itself...........
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223152 tn?1346978371
Hi jules and can

Got to agree with you both!  I missed the part about there only being one nucleitide left in trials.  That is not  good. Jules, the GS-7977 sounds so very promising but so many people can not or should not wait!

I had my annual physical last week and I asked my doctor if he was starting to test everyone born between 1945 - 1965 for hep C and he said he was.  Any surprises, I asked?   None yet, he said.  But to that I added that I had been a blood donor for years before they were able to test blood for hep C - before they even knew what it was.  I do think everyone who has had a blood transfusion prior to 1993 should be tested too.
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Avatar universal
Morning Cando and Bean!  Having only the GS-7977 in advanced stages makes me a little nervous.  These big pharma companies need to get back to the drawing board yesterday.  With all of these natural disasters happening and people donating blood to help others I can only imagine the increase in Hep C dx.  And I am afraid people who are borderline on their biopsies, whether to treat now or wait, are going to wait for the all orals thinking they will be available right around the corner. JMHO

Jules
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Avatar universal
" Fortunately there are other trials continuing with much better outcomes"

That is very true, but like the good doctor states, were not there yet.

"The suspension of this drug family leaves only 1 nucleotide at an advanced stage of development (sofosbuvir, previously known as GS-7977), and I am now crossing
my fingers and hoping that its current impressive safety record continues."

Hope all is well Bean
Helpful - 0
223152 tn?1346978371
Good morning , can. This is unfortunate but it sounds like necessary.  Fortunately there are other trials continuing with much better outcomes.  This - a possiblility of pancreatits or  cardoitoxicity - is an absolute reason to back down.

I even wish Vertex and Merck had worked a little harder to try to get rid of the side effects from the PI's although they are not near as bad as this.

" I remind my patients that waiting for new drugs is not entirely risk free, and if a decision to wait for better drugs is made, it is important to review the decision in a few months to see if the changing drug development landscape necessitates a review of the original "

However, my friend, you and I agree on this statement whole heartedly.

bean

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Avatar universal
PART 2

Implications
The recent concerns with licensed and unlicensed drugs serve as a salutary reminder of the difficulties of drug development. As patients and clinicians who are awaiting the arrival of interferon-free treatment regimes, we should remember that excellent responses in small patient cohorts do not guarantee eventual success. As we wrestle with the decision of whether to treat now or wait for more effective regimens, we need to keep in mind that we still have hurdles to overcome before we can celebrate safe, effective all-oral combination therapy for HCV. In my clinic, I remind my patients that waiting for new drugs is not

entirely risk free, and if a decision to wait for better drugs is made, it is important to review the decision in a few months to see if the changing drug development landscape necessitates a review of the original

decision. The large lady is on the stage, but the show is not yet over.

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/ClinicalThought/Thought01.aspx
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