ChromaDex agrees with FDA on NMN decision

ChromaDex Inc., the marketer of a healthy aging ingredient called Tru Niagen, said in a regulatory filing that the Food and Drug Administration has made the “correct” determination that nicotinamide mononucleotide (NMN) does not meet the definition of a dietary supplement.

Los Angeles-based ChromaDex markets a proprietary form of nicotinamide riboside ("NR"), a so-called NAD+ (nicotinamide adenine dinucleotide) precursor, which ChromaDex characterized as a “superior” alternative to NMN in a Jan. 9 filing with FDA.

ChromaDex submitted its comments to a regulatory docket that FDA opened in response to a citizen petition from the Natural Products Association and Alliance for Natural Health USA. In March 2023, the groups requested FDA reverse its position that NMN is excluded from the definition of a dietary supplement or commit to exercising so-called enforcement discretion.

In late August, six months after the petition was filed, FDA advised the petitioners it had not reached a decision “due to competing agency priorities.”

In the fall of 2022, FDA determined NMN – an ingredient marketed at the time on Amazon for such health conditions as anti-aging and energy production – cannot be sold in dietary supplements due to being investigated as a pharmaceutical drug.

Related:NMN is precluded in supplements, says pharma company to FDA

A clinical-stage pharma company, Metro International Biotech LLC, is investigating the use of a proprietary form of NMN called MIB-626 to treat medical conditions, including Alzheimer’s disease. In a 12-page letter written to FDA in November, Metro agreed with FDA that NMN is properly barred from being marketed as a dietary supplement under the so-called drug preclusion clause of the Federal Food, Drug & Cosmetic Act (FDCA).

ChromaDex, whose NR competes with NMN, also has reached the same conclusion, and it described as “patently unfounded” claims by the supplement sector that it was unaware NMN was being pursued as an IND (investigational new drug) while the industry was investing in the development of NMN as a dietary supplement.

“Despite the confidential nature of when and how articles are authorized as INDs, the pursuit of NMN as a drug candidate was overtly evident based on publicly available information,” ChromaDex asserted.

For instance, the company cited a March 23, 2017, newspaper article in the British Daily Mirror that reported on plans to begin testing NMN on clinical trial patients. In another article published around the same time and cited by ChromaDex in its FDA filing, the UNSW (University of New South Wales) Sydney wrote, “An international team including UNSW researchers has made a discovery that could lead to a revolutionary drug that actually reverses ageing, improves DNA repair and could even help NASA get its astronauts to Mars.”

Related:FDA official concedes, ‘We didn’t connect those dots’ in reviews of NMN

Harvard Medical School Professor David Sinclair, Ph.D. – a co-founder of Metro International Biotech – was quoted in both stories.

“This is the closest we are to a safe and effective anti-ageing drug that’s perhaps only three to five years away from being on the market if the trials go well,” the UNSW Sydney article quoted Sinclair.

ChromaDex also noted clinical trials using MIB-626 were registered on clinicaltrials.gov in 2021.

FDA received backlash following its determination that NMN was excluded in dietary supplements because it previously had acknowledged an ingredient notification from a Chinese-based supplier of NMN. In a May 16, 2022, letter to SyncoZymes (Shanghai) Co. Ltd. made public in July of that same year, FDA acknowledged the company’s NDI (new dietary ingredient) notification without an objection.

These notices are provided to FDA to demonstrate the safety of an NDI under a requirement in the Dietary Supplement Health and Education Act of 1994 (DSHEA).

In an interview last year with Natural Products Insider, an FDA official acknowledged the agency had not initially “connected the dots” in its evaluation of NMN. The agency changed its mind about the status of NMN after learning the ingredient was the same article as MIB-626.

Related:FDA says ingredient studied as drug—β-NMN—is excluded from supplements

“Once we were able to make that connection that NMN … was the subject of an IND [investigation new drug application] under authorization,” FDA verified “it checked all the boxes and then we communicated that to the notifier,” FDA Office of Dietary Supplement Programs Director Cara Welch, Ph.D., said. “Because of the unfortunate situation, we felt it was really important to communicate that to everyone who had submitted a notification for that ingredient.”

In its regulatory filing, ChromaDex characterized as “disingenuous” the argument that FDA’s NMN determination “stifles innovation and deprives consumers of a vital healthy aging product.”

“Prior to FDA’s ruling in November 2022, on any given day over 200 brands of NMN-containing products appeared for sale on Amazon. It can be presumed that few, if any, of these brands invested in science or quality in any appreciable way,” ChromaDex wrote to FDA. “Our own analysis of top-selling NMN brands at the time revealed that the majority failed to contain the claimed amount of NMN, and many contained none.”

Last year, Amazon prohibited supplement brands from selling NMN through its e-commerce platform.