{"id":30229,"date":"2012-07-05T19:14:39","date_gmt":"2012-07-05T23:14:39","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=news&p=30229"},"modified":"2012-07-09T08:41:59","modified_gmt":"2012-07-09T12:41:59","slug":"stem-cell-therapy-company-hypes-preliminary-results","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/07\/05\/stem-cell-therapy-company-hypes-preliminary-results\/","title":{"rendered":"Stem Cell Therapy Company Hypes Preliminary Results"},"content":{"rendered":"

A biotech company has been accused of releasing preliminary and misleading information about a clinical trial. The company,\u00a0Osiris Therapeutics, is the manufacturer of \u00a0a cultured\u00a0mesenchymal stem cell (MSC) therapy called\u00a0Prochymal, which is being studied in\u00a0a phase 2, placebo-controlled trial in post-MI patients<\/a>. Earlier this week, Osiris issued\u00a0a press release<\/a>\u00a0announcing preliminary results from the trial, in which 220 patients have been randomized, claiming that Prochymal \u201csignificantly reduces hypertrophy,\u00a0arrhythmia and progression to heart failure in patients suffering a heart attack.\u201d But Adam Feuerstein, a veteran biotech reporter for\u00a0The Street<\/em>,\u00a0accuses the company of distorting the truth about the trial<\/a>.<\/p>\n

Osiris \u201cdisappeared\u201d important data in its press release, Feuerstein writes in his detailed analysis. He quotes the press release:<\/p>\n

Patients receiving Prochymal had significantly less cardiac hypertrophy, as measured by cardiac MRI, compared to patients receiving placebo (p [less than] 0.05). Patients treated with Prochymal also experienced significantly less stress-induced ventricular arrhythmia (p [less than] 0.05).<\/p><\/blockquote>\n

Feuerstein comments:<\/p>\n

Sounds impressive except none of the Prochymal benefits disclosed by Osiris are predefined endpoints in the phase II trial. Osiris appears to have thrown out the real endpoints called for in the phase II trial and replaced them with new endpoints which just happen to show Prochymal in the best light. Why would Osiris do this? Perhaps the pre-defined endpoints in the study all failed? That\u2019s a pretty safe assumption when companies decide to swap out trial endpoints with no disclosure or explanation.<\/p><\/blockquote>\n

Feuerstein points out that the primary endpoint of the trial, as listed on ClinicalTrials.gov<\/a>, is\u00a0left ventricular end systolic volume (ESV), while the secondary endpoints are left ventricular ejection fraction (LVEF), infarct size, and major adverse cardiovascular events. Writes Feuerstein: \u201cOsiris\u2019 silence on the outcomes of these two important endpoints [ESV and LVEF] should be deafening to investors \u2014 and not in a good way.\u201d<\/p>\n

The Osiris press release also claims \u201ca statistically significant reduction in heart failure\u201d:<\/p>\n

In the study, seven patients who were treated with placebo have progressed to heart failure requiring treatment with intravenous diuretics, compared to none of the Prochymal patients (p=0.01). Furthermore, patients receiving placebo tended to require re-hospitalization for cardiac issues sooner than the patients receiving Prochymal (median 27.5 days vs. 85.5 days).<\/p><\/blockquote>\n

However, as Feuerstein writes, \u201cthese weren\u2019t predefined endpoints\u201d:<\/p>\n

Importantly, Osiris doesn\u2019t disclose the time point at which these purported benefits occurred, nor does the company tell us anything about the number of patients analyzed. How was heart failure defined? Osiris doesn\u2019t say. What was the baseline incidence of heart failure in the study? Osiris doesn\u2019t say. The study only allowed for a single infusion of Prochymal or a placebo immediately after the first heart attack but patients were followed for six months or a year, so how do follow-up therapies in each arm of the study compare? Were they balanced? Again, Osiris doesn\u2019t say.<\/p><\/blockquote>\n

In the press release, a company official announces an extension of the trial’s duration:<\/p>\n

Given the quality of the data and highly encouraging results observed thus far, we are extending the trial\u2019s duration to capture a better understanding of the long-term clinical benefits of MSCs.<\/p><\/blockquote>\n

But the company offers no explanation for the extension. Writes Feuerstein:<\/p>\n

Perhaps Osiris is extending the phase II study to delay the reporting of negative results? Again, that\u2019s a pretty safe assumption absent a better explanation.<\/p><\/blockquote>\n

Update (July 6)\u2013\u00a0 I have heard from several investigators in the trial that the Osiris press release was issued without any input or consultation from the site investigators. In fact, the site investigators, including several who are\u00a0 extremely experienced clinical trialists, have expressed frustration and disappointment because their input has not been sought at any point during the trial. In most multicenter trials it is common practice to consult with the sites, and in particular the top-enrolling sites. In this case, the highest enrolling sites have had no significant involvement in the trial design or conduct. One investigator said he \u201chad never worked with a company like this.\u201d<\/p>\n

Another member of the steering committee told me that the committee had not met in a long time and has not seen the trial data. In fact, steering committee members were not even aware that Mark Vesely, an assistant professor at the University of Maryland, was the principal investigator of the study. One steering committee member said he\u2019d never heard of him before reading the press release.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

A biotech company has been accused of releasing preliminary and misleading information about a clinical trial. The company,\u00a0Osiris Therapeutics, is the manufacturer of \u00a0a cultured\u00a0mesenchymal stem cell (MSC) therapy called\u00a0Prochymal, which is being studied in\u00a0a phase 2, placebo-controlled trial in post-MI patients. Earlier this week, Osiris issued\u00a0a press release\u00a0announcing preliminary results from the trial, in […]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[14,9],"tags":[740],"class_list":["post-30229","post","type-post","status-publish","format-standard","hentry","category-heart-failure","category-interventional-cardiology","tag-stem-cell-therapy"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/30229","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=30229"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/30229\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=30229"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=30229"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=30229"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}