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What is CLEAR Wisdom?

It sounds like something from your doctor of philosophy and your brain, but it’s really about a potentially valuable new treatment for your heart. If you visit ClinicalTrials.gov (the major site for any US study), you will see that the unique number for this study is NCT 02991118. This is a long-term study of a new drug called bempedoic acid (no brand name as yet since it is investigational), which also goes by ETC 1002.

This study has several things going for it:

  • The drug works in a new way to lower cholesterol and is actually also being studied in a different study combined with an older medicine to see if this gets even stronger results.
  • It is a long-term study, meaning that it will most likely have continued for enough time to show TRUE BENEFITS as well as uncovering possible risks.
  • This isn’t a study of healthy people with minimal chance of having problems. CLEAR Wisdom is looking at people with increased levels of abnormal lipids (hyperlipidemia) at HIGH RISK of heart and blood vessel (cardiovascular) problems.
  • The study has a reasonable patient (sample) size of roughly 700 people.
  • It is a trial of bempedoic acid added to adults with high cholesterol.
  • You only have to take this medicine once a day.
  • It’s being presented at a major heart meeting (The American College of Cardiology) with a balanced and objective discussion.

Why could this study be important?

Many many patients have problems tolerating (Statin intolerance) the widely used family medicines known as HMG-CoA Reductase inhibitors (AKA statins). The names are familiar because they all end in statin (rosuvastatin-Crestor, atorvastatin-Lipitor, etc.).

There is a clear unmet medical need for a new agent that avoids statin mechanisms of action—bempedoic acid works on liver specific ATP-citrate lyase (trust me, this is a different way of working versus statins.

As always, we have to wait for the ACC meeting and for the FDA to approve the medicine, but this phase 3 study (the last phase before FDA approval) holds great promise!

For additional information, look at the study itself on clinicaltrials.gov. We will be attending the ACC meeting in March and will post and blog more as the news becomes available!

  1. Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PH, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038/ncomms13457.
  2. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.
  3. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489. Epub 2015 Jun 3.
  4. Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013 Mar;19(2):139-49. Review.
  5. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45   10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2015 Dec 22;132(25):e396. Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8.

True Breakthroughs

But when will the CREDENCE results on Invokana be published?

You may remember that the CREDENCE study was stopped early July 16, 2018 --the “Phase 3 CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) clinical trial, evaluating the efficacy and safety of INVOKANA® (canagliflozin) versus placebo when used in addition to standard of care for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), is being stopped early based on the achievement of pre-specified efficacy criteria.”

OK then, but WHEN will we know the results (usually released at a major conference).

Would you like to know the answer?

April 15, 2019 at the World Congress of Nephrology in Melbourne, Austrailia.

We of course, will update our current Essential Guide to Prescription Drugs, Update on canagliflozin, CREDENCE for Invokana eBook at that time. The beauty of breaking science is that it will highlight the 4,401 patients who were in the study AND bring the benefits of those patients to a broader patient population while helping prevent problems in those living with diabetes.

Remember, as the lead CREDENCE researcher said: "Nearly half of all people with type 2 diabetes will develop chronic kidney disease, causing a high risk of kidney failure and cardiovascular disease, and impacting their quality and length of life, even with the current best available care. This huge unmet need is why it was so important for us to initiate the landmark CREDENCE renal outcomes trial over four years ago," said Vlado Perkovic, M.B.B.S, Ph.D., F.A.S.N., F.R.A.C.P., CREDENCE Steering Committee co-chair, Professor of Medicine, University of New South Wales Sydney, and Executive Director, The George Institute for Global Health Australia. "We have accepted the advice of the Independent Data Monitoring Committee to stop the CREDENCE trial early due to demonstration of efficacy, and look forward to sharing the findings as soon as possible."

See the True Breakthrough criteria below

True breakthrough Criteria: What criteria will we use?

  1. The medicine is the first in a new medicine family (class)…what the FDA would call a novel therapeutic entity (visit www.FDA.gov). A good example here would be evolocumab (Rapatha), the first member of the PCSK9 inhibitor family which was approved.
  2. The medicine is 20% or more effective in treating or preventing a prevalent disease or condition than prior medicines. For example, the new prescription fish oil (Vascepa) which was found to prevent heart attacks by 25% in people who were already being treated with statins.
  3. The therapeutic concept targets a novel path or uses a novel approach to modify or prevent or cure disease. An example here would be signal transduction inhibitors such as Gleevec (actually turns off a gene to cure stomach cancer) or immune based therapies such as ipilimumab (Yervoy) for melanoma. CRISPER technology seeking gene-based cures.
  4. New guidelines which radically change current practice, incorporating new approaches to monitoring therapy or preventing disease. A good example here are the 2018 American Diabetes Association standards of care.
  5. A company making a medicine develops a program or radical pricing which confers new access to care or enhances outcomes (results) by 15% versus other approaches or therapies. The latest example here is the company Amgen and the medicine Rapatha. The company decided to lower the cost of the medicine by 60%, which is expected to give huge increases in access to a very effective cholesterol medicine.
  6. A new medicine results in CURES of a particular disease or condition where none was previously available. A great example here are the hepatitis C treatments (Harvoni, others) which can result in CURE of the hepatitis C.
  7. A laboratory, clinic or point of care test that improves the ability to diagnose or predict a disease or condition which either could not be previously reliably predicted.
  8. A medicine, vaccine or mechanical device that PREVENTS a disease or condition to a significantly greater degree than previously possible or which addresses a disease or condition previously perceived as a natural course of aging or which was not able to be prevented. A great example here is the new Shingles vaccine.

Real medicine, real research, really important. The Essential Guide to Prescription Drugs is always there for you!

References

  1. FDA www.fda.gov
  2. NIH https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Updated September 24, 2017. Accessed September 10, 2018.
  3. The Use of Essential Drugs. World Health Organization, apps.who.int/medicinedocs/en/d/Js2281e
  4.  Accessed 10 31 2018. http://sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/  
  5. Conference materials accessed 1/12/19: World Congress of Nephrology.

 

Have you heard about the REDUCE-IT study?

For those attending the American Heart Association meeting in Chicago By James Joseph Rybacki, Pharm.D. 1/8/19

On November 10-14 2018, you could have heard a pin drop in the large conference room when Dr. Deepak Bhatt presented the results. The results showed a relative risk reduction of 25% in Major Cardiac Adverse Events (MACE). This study looked at more than 8,000 people who were already taking statins, had heart disease and may also have been diabetic.

It’s not my first rodeo and even I was impressed by these results. Interestingly, many of you know I have a history of heart disease and suffered an early heart attack in 2005. Despite this, and despite the new REDUCE-IT data, my insurance carrier REFUSED to pay for Vascepa, although my doctor sent in two requests saying that the medicine was warranted.

The problem stems from the product labeling (although huge numbers of prescriptions are written off-label in the US). Who will pay for the drug? For now, me. I have been absorbing the two hundred dollar expense because I think that the data are simply that good. Will the label for Vascepa change? This remains a decision for the FDA. In the interim, I think US insurance companies who attempt to deny heart patients this valuable medicine are short sighted and are WRONG. We have a new video on Vascepa on www.EssentialGuideToPrescriptionDrugs.com.

What on earth is the controversy over PCSK9 medicines for cholesterol.??

By James Joseph Rybacki, Pharm.D. 1/8/19

Hmmmm, it comes down to money, or it used to, or, it still does. Let’s take a closer look. The challenge for the two novel cholesterol medicines in the PCSK9 family (evolocumab Repatha and Alirocumab or Praluent) has NOT been lack of use because they don’t work, it has been failure of insurance companies to pay the roughly $12,000 dollars per year that they cost. Let me repeat that. COST, NOT results has been the key reason that these extremely effective and safe medicines have not been widely used.


A study released at the Heart Association meeting in Chicago Nov 11, 2018 showed that the ODYSSEY Outcomes trial found Praulent is cost-effective when the price is $6,319 a year when the willingness-to-pay threshold is at a usually accepted $100,000 per QALY (Quality Adjusted Life-year). The author, Deepak Bhatt from the Brigham and Women’s hospital expressed his hope that this analysis might provide evidence for what the price should be, versus market pricing that uses expense that might be tolerated.


Interestingly, the Repatha manufacturer (Amgen) lowered the price of Repatha to $5,850 per year last October. It will be interesting to see how Repatha sales are impacted by this novel pricing.

Did you think that Twitter would become mainstream medicine?

By James Joseph Rybacki, Pharm.D. 1/8/19

I wasn’t so sure when I decided to call myself Rybackiknows. Sounded pompous at first, then had a certain ring to it. Thousands of tweets later, I think of it in the same light at LinkedIn.

I remember reading “Medicine in the age of Twitter in the NY Times in 2009. At that time Pauline Chen, MD was reflective and it was noted that more than 60% of Americans went on line for medical information. Yikes.

If we jump to 2017, we find Vinay Prasad challenging his medical colleagues via Twitter and doing a righteous job of it as well. I’ve found myself roundly criticized at times, but then, if you are saying something worthwhile, this is bound to happen from time to time. Is Twitter the appropriate place for patient discussions or consultations, definitely no, but Twitter does have a place in mainstream medicine IF you manage by data and accurately quote the facts.





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