{"id":8005,"date":"2016-01-29T16:56:45","date_gmt":"2016-01-29T21:56:45","guid":{"rendered":"http:\/\/blogs.nejm.org\/hiv-id-observations\/?p=8005"},"modified":"2016-02-03T10:25:17","modified_gmt":"2016-02-03T15:25:17","slug":"elbasvirgrazoprevir-combination-pill-for-hcv-a-welcome-new-option-with-a-few-buts","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/elbasvirgrazoprevir-combination-pill-for-hcv-a-welcome-new-option-with-a-few-buts\/2016\/01\/29\/","title":{"rendered":"Elbasvir\/Grazoprevir Combination Pill for HCV a Welcome New Option — With a Few Buts"},"content":{"rendered":"

\"zep<\/a>As expected, there’s a new option for HCV therapy, the combination pill elbasvir\/grazoprevir<\/a>\u00a0(EBR\/GZR, brand name Zepatier<\/em>, more on this below), and it’s indicated for genotypes 1 and 4. For those mechanistically inclined, elbasvir is an NS5A inhibitor (like ledipasvir), and grazoprevir is a protease inhibitor (like simeprevir).<\/p>\n

This is the second one-pill, once a day option for HCV, and unlike the first (ledipasvir\/sofosbuvir, or LDV\/SOF), it can be used in patients with end-stage renal disease on hemodialysis — an advantage that granted the regimen a “breakthrough therapy” designation, speeding FDA approval.<\/p>\n

In addition, the list price is substantially lower — $54,000 for 12 weeks of EBR\/GZR, vs $94,000 for LDV\/SOF. Of course the actual price paid by government and private payers is heavily negotiated<\/a>, so how the two will compare remains to be seen. And some providers are treating their low viral load genotype 1 patients with just 8 weeks of LDV\/SOF therapy, bringing the price much closer to $54,000 (at least in those cases).<\/p>\n

But\u00a0why<\/em> the lower price? After all, cure rates are outstanding (94-97% for genotype 1), side effect rates low, and you can’t get simpler than one pill a day.<\/p>\n

Seems to me there are two major reasons:<\/p>\n

    \n
  1. They’re not the first.<\/strong> LDV\/SOF has been available for over a year, and providers are incredibly comfortable with it. Plus, you can barely take a walk down the street, turn on the radio in your car, or flip on the TV without encountering a direct-to-patient advertisement for LDV\/SOF. This lower price will be an important strategy for convincing providers, patients, and payers that EBR\/GZP is an option.<\/li>\n
  2. It’s not quite as convenient as LDV\/SOF. \u00a0<\/strong>A patient starting HCV with EBR\/GZR is somewhat less\u00a0likely\u00a0to be taking just one pill a day for 12 weeks than if treated with LDV\/SOF.<\/li>\n<\/ol>\n

    The reason for this slightly greater complexity is that one of the predictors of treatment failure in studies of EBR\/GZR was the pre-treatment presence of certain NS5A polymorphisms — which are similar to\u00a0resistance mutations:<\/p>\n

    \"erb-gzr<\/a><\/p>\n

    Providers will need to do a pre-treatment\u00a0test for these polymorphisms.\u00a0Based on these results and the treatment history, here are the treatment recommendations<\/a> for the EBR\/GZR regimen:<\/p>\n

    \"elb-gzp<\/p>\n

    And how common are the polymorphisms? Per the package insert, “The prevalence of\u00a0polymorphisms at any of these positions in genotype 1a-infected subjects was 11% (62\/561) overall, and 12% (37\/309) specifically for subjects in the U.S. across Phase 2 and Phase 3 clinical trials …”<\/p>\n

    Furthermore, as noted above, some of the regimens will also need to be extended to 16 weeks, and the prescribing information recommends LFT monitoring during treatment for all patients. Drug-drug interactions are also more common than with LDV\/SOF.<\/p>\n

    These issues notwithstanding, EBR\/GZR\u00a0is a simpler treatment than the “PrOD” regimen (paritaprevir, ritonavir, ombitasvir, and dasabuvir) — and for the record less expensive than that one, too.<\/p>\n

    Not only that, the brand name (Zepatier!)<\/em>\u00a0offers a nice French souffle\u00a0to our existing Italian baked pasta with cheese\u00a0(Harvoni!).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    As expected, there’s a new option for HCV therapy, the combination pill elbasvir\/grazoprevir\u00a0(EBR\/GZR, brand name Zepatier, more on this below), and it’s indicated for genotypes 1 and 4. For those mechanistically inclined, elbasvir is an NS5A inhibitor (like ledipasvir), and grazoprevir is a protease inhibitor (like simeprevir). This is the second one-pill, once a day […]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8],"tags":[1116,417,1117],"class_list":["post-8005","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care","tag-elbasvirgrazoprevir","tag-hepatitis-c","tag-ledipasvirsofosbuvir"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/8005","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=8005"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/8005\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=8005"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=8005"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=8005"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}