{"id":44903,"date":"2014-08-28T12:55:36","date_gmt":"2014-08-28T16:55:36","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=44903"},"modified":"2014-08-28T15:52:43","modified_gmt":"2014-08-28T19:52:43","slug":"predicting-paradigm-hf-or-what-to-expect-when-youre-expecting","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/08\/28\/predicting-paradigm-hf-or-what-to-expect-when-youre-expecting\/","title":{"rendered":"Predicting PARADIGM-HF, or What to Expect When You’re Expecting"},"content":{"rendered":"

This blog also appears on Forbes.com<\/a>.<\/em><\/p>\n

The wait is almost over. For the last 5 months the most eagerly awaited trial in the cardiovascular universe has been PARADIGM-HF, the large (8,500 patient) trial of a new and novel heart failure drug from Novartis. If reality lives up to the early hope and hype, the drug, LCZ696, could completely reshape the heart failure landscape and give Novartis that rarest of gems, a new and genuine blockbuster cardiovascular drug.<\/p>\n

The main results of the trial will first be presented at a press conference in Barcelona, Spain this Saturday in connection with the annual meeting of the European College of Cardiology. As I have previously reported<\/a>, the PARADIGM-HF trial was stopped because of a highly statistically significant reduction in cardiovascular mortality in patients taking LCZ696 (a novel, first-in-class Angiotensin Receptor Neprilysin Inhibitor) instead of the current gold standard of treatment, an ACE inhibitor.<\/p>\n

Until we see the data it is impossible to reach any conclusions, but, as might be expected, Wall Street analysts have been reading the tea leaves and trying to figure out likely outcomes.<\/p>\n

One analyst, Timothy Anderson of Sanford Bernstein, remains cautious, despite \u201cinvestor excitement\u201d over comments<\/a> made by the company and the co-principal investigator of PARADIGM-HF, Milton Packer. He noted that Novartis \u201chas sometimes overpromised and underdelivered,\u201d so he\u2019s waiting to see the results. He currently thinks LCZ696 could reach annual sales of 2.4 billion in 2020. His estimates could grow if the results of PARADIGM are extremely impressive. Currently, according to Anderson, \u201canalysts’ opinions are jelling around a high teens to 20%\u201d reduction in the primary endpoint of cardiovascular death and heart failure hospitalizations.<\/p>\n

\u201cThis would be viewed as meaningful\u2014anything more would be fantastic,\u201d said Anderson. Of course the analysts, along with everyone else, will also be looking at other issues like safety and tolerability, including, especially \u201cany red flags about angioedema,\u201d which ruined a similar BristolMyers Squibb drug, omipatrilat, some years ago.<\/p>\n

One striking feature of the current situation is that LCZ696 stands alone. Anderson is unaware of any other similar drugs in mid or late phase development. On the one hand, this may be good for Novartis. \u201cThe runway is very clear for a very long time,\u201d said Anderson. On the other hand, Novartis won\u2019t benefit from the combined effect\u2014seen with both ACE inhibitors and ARBs in the past\u2014of multiple companies working to develop the market. Efforts \u201cto supplant\u201d the very well established ACE inhibitors and ARBs will require \u201ca paradigm shift\u2026 that could take a long time to take into effect.\u201d<\/p>\n

Another analyst, Larry Biegelsen at Wells Fargo, wrote that PARADIGM-HF is \u201carguably the most important heart failure drug trial in almost 25 years.\u201d<\/p>\n

Morgan Stanley analysts calculate that Novartis\u2019s stock price now assumes expected peak sales of LCZ696 of more than $5.5 billion. To achieve these sales the drug \u201cwould need to be used in ~75% of the eligible patient population.\u201d Morgan Stanley then surveyed cardiology key opinion leaders (KOLs). In order to replace ACE inhibitors as the standard of therapy, they said the trial would need to show at least a 25% relative risk reduction in the primary endpoint and at least a 20% reduction in cardiovascular death.<\/p>\n

The Morgan Stanley survey also notes that KOLs (and, surely, plain old cardiologists as well) will be just as interested in the absolute differences between the two treatment arms, as reflected in the number needed to treat, or NNT, as in the relative risk reductions. The KOLs said an NNT of 25-30 would encourage a shift to LCZ696.<\/p>\n

Novartis has told analysts that LCZ696 could become the biggest product in the company\u2019s history. The current record holder is Diovan (valsartan), which had peak sales of $6 billion.<\/p>\n

One thing we know for certain: I\u2019ve been told by a reliable source that LCZ696 will not gain a new name at the ESC. For now we\u2019re stuck with this awkward moniker.<\/p>\n","protected":false},"excerpt":{"rendered":"

Larry Husten analyzes the expectations surrounding the upcoming release of PARADIGM-HF and its centerpiece LCZ696 from the perspective of the medical field as well as the world of economics.<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,14],"tags":[512,2221,2352,287,2351,1903,2350,1407],"class_list":["post-44903","post","type-post","status-publish","format-standard","hentry","category-general","category-heart-failure","tag-ace-inhibitors","tag-angiotensin-receptor-neprilysin-inhibitor","tag-ecc","tag-heart-failure-2","tag-lcz696","tag-novartis","tag-paradigm-hf","tag-pharmaceutical-industry"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/44903","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=44903"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/44903\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=44903"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=44903"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=44903"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}