HEALTH TECH
SHIV GAGLANI
A New Niacin Formulation ?
Looking to Reduce Niacin Side Effects via a Novel Drug Combination
Joseph Habboushe , MD , an emergency physician in New York City , is a serial entrepreneur who not only helped create MDCalc ( profiled in the April issue of CSWN ), but also recently launched Vitalis Pharmaceuticals . He developed the core technology for a niacin formulation that has been shown in trials to reduce side effects such as flushing . We spoke with him about his latest company .
What is being developed at Vitalis ? Aspirin is recommended as a pre-treatment for a few medications to reduce a compliance-limiting flush side effect . However , most patients have trouble complying with the timing for a pre-treatment , so we developed a novel aspirin formulation that solves this problem . Our pill allows for simultaneous ingestion of aspirin and the drug . Our two primary combinations are aspirin with high-dose niacin ( VTS-63 ), for high triglycerides & dyslipidemia , and aspirin with a fumaric acid ( VTS-72 ), such as Biogen ’ s Tecfidera , currently the most widely used oral drug for multiple sclerosis .
How did you develop the idea for Vitalis ’ s drugs ? The idea first came to me about 10 years ago , when I was finishing medical school . It seemed ludicrous : patients wouldn ’ t take a great cholesterol drug ( niacin ) because of a non-dangerous flushing side effect . Aspirin , which also prevents damage from heart attacks and strokes , could cut the flush in half . Yet most people wouldn ’ t take the aspirin because they had to do so 30 minutes ahead of the primary drug .
There had to be a better way . So I started really studying aspirin - one of the oldest yet most intriguing drugs on the planet ( there are full text books on it ). The ideas developed into small experiments and eventually into a double-blind ransomized controlled trial completed last year at Harvard and Drexel Universities . We named our formulation VTS-Aspirin .
What are its applications ? What studies have you done that show efficacy ? Our early unblinded niacin study showed a 53 % reduction of flush , and a later placebo-controlled Harvard / Drexel study showed a 38 % flush reduction — both statistically significant . 1 Compare this with ER niacin which , dose-for-dose , only had
25-30 % flush reduction compared with immediate release ( IR ) niacin . Our flush reduction is in addition to that of ER niacin .
We also do not anticipate any new side effects , as we aren ’ t using a new molecule to reduce the flush — just aspirin . What ’ s great about VTS-Aspirin is that it probably works with any drug that causes the “ niacin flush ” ( that is , agonists of the “ niacin receptor ” GPR109A ). The most clinically significant are fumaric acids such as dimethyl fumarate ( branded as Tecfidera ), which are disease-modifying in multiple sclerosis . Up to 60 % of fumaric acid patients experience the niacin flush . We ’ ve also done small studies using VTS-Aspirin combinations for headache , and it seems to show some benefit .
Isn ’ t there controversy surrounding use of niacin ? This is true . Niacin ’ s role in dyslipidemia has been questioned in the wake of Merck ’ s HPS2-THRIVE trial . 2
Merck was developing their own low-flush niacin , combining generic Niaspan ( ER niacin ) with their proprietary flush-reducing agent , laropiprant . Perhaps because laropiprant was a new , untested molecule , the FDA requested a full outcomes trial . The study missed its primary endpoint . Initial headlines announced that niacin ( as a cholesterol drug ) may be dead .
But there are several criticisms of the HPS2- THRIVE trial design :
1 . It didn ’ t target just those we would normally prescribe niacin ( i . e . those with a less-than-perfect cholesterol panel ). Rather , all subjects were on statins , with an impressively low average LDL < 80 . In some ways , a positive study would have been surprising , and greatly increase the number of eligible patients .
2 . Laropiprant is likely a dirty drug . New side effects found in the treatment arm of HPS2 — increased infection and bleeding — were attributed to niacin . And as there were only two arms , niacin plus laropiprant , or placebo , it became difficult to figure out which medication was responsible . A recent Bayesian analysis suggested it ’ s likely due to laropiprant . Small animal studies of laropiprant seem to support this as well .
3 . Forty percent of the HPS2-Thrive subjects were in China , a population that historically has not done well on niacin .
Finally , when you dig into the results , niacin actually did work , at least in the subgroups you may expect it to . It ’ s right there in the HPS2-THRIVE “ Supplementary Appendix ,” separately downloadable from the New England Journal of Medicine website . Specifically , statistically significant MACE reduction in patients with LDL > 77 ; patients taking beta blockers ; smokers ; and those with the highest Apo B levels . It also trended toward significance when removing the Chinese patients ( p = 0.06 ), and also in all male patients ( p = 0.07 ).
In other words , when you dig into it , HPS2-THRIVE seems to confirm what we thought before : niacin is beneficial when given to the right patients . It ’ s not for everyone . Those who know niacin well get this .
Where is Vitalis right now with the drug ? Development . We are working on our two primary drugs , VTS-63 ( ER Niacin + VTS-Aspirin , for dyslipidemia ) and VTS-72 ( Fumaric Acid + VTS-Aspirin , for multiple sclerosis ). We are raising a small round of funding to allow us to do the studies necessary to prove safety and efficacy . If things go well our medications may be helping patients in a year or 2 .
Who else is working with you on this ? We have a small core team . So much of drug development can be outsourced . We don ’ t just search for individuals with talent , but also people with the same sense of ethics , curiosity , and drive that we have .
Do you have advice for clinicians hoping to develop their own drugs / devices ? Keep in mind that clinicians have a better understanding of patient needs than anyone in the healthcare industry . We know what works , and what doesn ’ t work . Let yourself dream up solutions to the problems and pain points that you know . There is nothing as useful in health care as innovation coming from a clinician . ■
Reference :
1 . Banka S , Thachil R , Levine A , et al . Comparison of incidence of niacin flush with difference formulations of aspirin ( poster ). CSHP 26th Annual Catch the Wave Conference . Nov . 13 , 2015 . Waterbury , CT .
2 . The HPS2-THRIVE Collaborative Group . N Engl J Med . 2014 ; 371:203-212 .
Disclosure : Dr . Habboushe is a co-founder of Vitalis LLC and has equity in the company . His views are his own .
Shiv Gaglani is an MD / MBA candidate at the Johns Hopkins School of Medicine and Harvard Business School . He writes about trends in medicine and technology and has had his work published in Medgadget , The Atlantic , and Emergency Physicians Monthly .
ACC . org / CSWN CardioSource WorldNews
53