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Re: EVAPORATE: Stopped for efficacy ... why I believe ... Relevance of MOA ... Ex"FDA
won't advocate for patients who can't take statins, and label will
contain "adjunct to statin therapy", because that's what R-IT was about -
they'll just let doctors be doctors and prescribe off label to patients
not on statins, but they won't promote that use, they can't. Insurers
are the only ones who potentially stand in the way of off label scrips." Of course REDUCE-IT (and presumably the sNDA) are "about" Vascepa being given to patients who are on statins. That's what was meant by my saying Amarin is "stuck" with the REDUCE-IT trial design. The extent to which FDA, however, is constrained by REDUCE-IT's design is up to FDA, and they should be guided by the scientific evidence, logic, and patients' best interests. FDA can (contrary to your assertion that "they can't"), if they choose to, approve a label saying Vascepa is indicated for not only patients receiving statins and whose TGs > 135 mg/dL, but also patients who are at high risk for CVD (similarly defined) but who are statin intolerant. The analysis would be something like this. 1. Does the evidence show that Vascepa's CVD risk reduction benefit is limited just to at-risk patients on statins, and if not, is there reason to believe it would benefit patients whose CVD risk would be addressable with statin but for such patients' statin intolerance? 2. No, REDUCE-IT shows that at risk patients who receive statins and EPA benefit, but it does not show that at risk patients who are statin intolerant would not benefit from Vascepa. The main reason REDUCE-IT and other studies involving EPA have used patients on statins is because statins' benefits in reducing CVD risk have been firmly established and it would be unethical to conduct a robust outcomes study and give some (all, depending on design) of the subjects no statin or a placebo for statin. 3. Yes, there is reason to think at risk patients who are statin intolerant might benefit from Vascepa. Vascepa's MOA is not, so far as is known, entirely dependent on co-administration of statins. This gets into a lot of the basic science of EPA, and after listening to Dr. Mason's presentation given at AHA (link previously posted), I am persuaded that EPA's MOA includes reduction of oxidative stress, reduction of systemic inflammation, reduction of (reversal of) endothelial dysfunction, regardless of whether statin is present. Maybe (maybe) not always to the same degree, because some of EPA's effects appear to be potentiated by statin. So, without the potentiating effect of statin, EPA's benefit might be less pronounced (we don't know whether or how much). 4. Vascepa reduces "residual risk," that is, whatever CVD risk (65-70%) remains after administration of statin to control LDL-C. At risk patients who are statin intolerant, and thus not receiving statin, have higher than 65-70% CVD risk. Their risk is perhaps as high as 100% risk, unless reduced by other agents, such as a PCSK9 inhibitor. They thus need, urgently, therapeutic intervention for (their higher) CVD risk even more than do statinized patients. It would be unreasonable to conclude that an agent (Vascepa) proven to reduce residual CVD risk should not be approved also for patients who can't tolerate a drug known to control LDL-C and to potentiate, in some respects, the MOA of Vascepa. 5. The other legitimate question would relate to safety. Is there reason to believe that consumption of EPA without statin would be unsafe? I have not studied the science on that point, but my intuition is that there is probably enough science out there to support the conclusion that co-administration of statin has nothing to do with EPA's safety. Also, whatever risk, if any, might arguably be associated with EPA monotherapy in a statin intolerant patient would have to be weighed against the potential benefits, and, again, I believe enough is known about EPA's MOA to say that its benefits in monotherapy would likely be substantial. Finally, to your last point, FDA could solve the insurance coverage barrier for statin intolerant patients if they would simply include in the label the words "and such patients who are statin intolerant." FDA "can" and may (if they choose to so exercise their authority) do so. I believe they should. I'm not predicting what FDA will do, just expressing the hope that they will consider it logically with patients' best interests in mind. |
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Msg # | Subject | Author | Recs | Date Posted |
4961 | Re: EVAPORATE: Stopped for efficacy ... why I believe ... Relevance of MOA ... Ex | Public_Heel | 0 | 9/22/2019 5:46:18 PM |