{"id":3133,"date":"2012-08-25T16:14:02","date_gmt":"2012-08-25T20:14:02","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=3133"},"modified":"2015-06-04T15:14:05","modified_gmt":"2015-06-04T19:14:05","slug":"on-hcv-these-questions-three","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/on-hcv-these-questions-three\/2012\/08\/25\/","title":{"rendered":"On HCV, These Questions Three"},"content":{"rendered":"

\"\"<\/a>In the fastest-moving area of ID drug development, answers are eagerly sought to the following questions three<\/a>:<\/p>\n

    \n
  1. What does the bad news on\u00a0BMS-986094 — formerly\u00a0INX-189 — mean for other investigational HCV nucleotides?<\/strong>\u00a0Severe cardiotoxicity<\/a>, fatal in one case, has ended the drug’s development. Importantly, nothing similar has thus far been observed\u00a0<\/a>\u00a0with the structurally-similar IDX184, but that drug has been placed on “clinical hold” by the FDA. By contrast,\u00a0the nucleotide GS-7977 is apparently different enough chemically that studies are for now continuing. One take-home message: drug development is risky business.<\/li>\n
  2. When will the alphabet soup of terms used to describe HCV treatment response be abandoned?<\/strong>\u00a0HCV treatment either works, and you’re cured, or it doesn’t. But because the treatment is so cumbersome and so long, there’s a whole slew of ways to describe how things are going before you get to that point.\u00a0Let’s see, there’s RVR<\/em> (rapid virologic response, or no virus detected at 4 weeks); eRVR<\/em> (extended rapid virologic response, or no virus detected at weeks 4 and<\/em> 12 — used in this study<\/a> of daclatasvir); EVR<\/em> (early virologic response, which really isn’t that early, because it’s week 12, and it can be either pEVR<\/em> — for “partial” — which means HCV RNA drops by more than 2 log but is still detected, or cEVR<\/em> — for “complete”, which means it’s undetectable); ETR<\/em> (end of treatment response, or no virus detectable at end of treatment); and of course SVR<\/em> (sustained virologic response, now available in \u00a0many flavors, depending on the week after stopping treatment you want to measure it — 2, 4, 8, 12, 16, 24,etc). For now, with IF\/RBV +\/- telaprevir\/boceprevir and “response-guided” therapy still ruling the day, we’re stuck with this mish-mosh of terms, but I suspect most of this\u00a0stuff will be irrelevant pretty soon, except for the bottom line — how many are cured? <\/em>Doesn’t that sound better than “How many are SVR-12’d?”<\/li>\n
  3. So when precisely will these new drugs become available?<\/strong> Seems pretty obvious right now that if you’ve got HCV and can<\/em> wait for better treatments, you should<\/em>. Treatment became more effective with telaprevir and boceprevir, but it also got more complicated, toxic, and expensive. Things have to get better, and they will — especially with interferon-free options. Regardless, no one knows exactly when these new drugs will be available for use outside of clinical trials — 2013-2014 a broad estimate — and all kinds of things could hold up their approval (see #1 above). Plus, some patients can’t and shouldn’t wait for better options because they have advanced liver disease. Just this last week, two such individuals came in for evaluation — both with HIV, both with prior treatment failure on IF\/RBV, both with Stage 3\/4 fibrosis on liver biopsy. Should they wait for daclatasvir, GS-7977, TMC-435,\u00a0ABT-450\/r +\u00a0ABT-333, etc? Probably not.<\/li>\n<\/ol>\n
    For the record …\u00a0what is<\/em> the airspeed velocity of an unladen swallow?<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"

    In the fastest-moving area of ID drug development, answers are eagerly sought to the following questions three: What does the bad news on\u00a0BMS-986094 — formerly\u00a0INX-189 — mean for other investigational HCV nucleotides?\u00a0Severe cardiotoxicity, fatal in one case, has ended the drug’s development. Importantly, nothing similar has thus far been observed\u00a0\u00a0with the structurally-similar IDX184, but that […]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,8,10],"tags":[25,27,263,395,408,417,927],"class_list":["post-3133","post","type-post","status-publish","format-standard","hentry","category-infectious-diseases","category-patient-care","category-research","tag-abt-333","tag-abt-450r","tag-daclatasvir","tag-gs-7977","tag-hcv","tag-hepatitis-c","tag-tmc-435"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/3133","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=3133"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/3133\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=3133"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=3133"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=3133"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}