Health Tech: A New Niacin Formulation?
Looking to Reduce Niacin Side Effects via a Novel Drug Combination
By Shiv Gaglani

CardioSource WorldNews | 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.

References:

  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.

Read the full May issue of CardioSource WorldNews at ACC.org/CSWN

Clinical Topics: Diabetes and Cardiometabolic Disease, Clinical Topic Collection: Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: CardioSource WorldNews, Aspirin, Dyslipidemias, Fumarates, Multiple Sclerosis, Niacin, Pharmaceutical Solutions, Triglycerides


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