Six years ago, in a townhouse in Santa Monica, Mario Danek, began tinkering on a device to help cigarette smokers quit. After buying nebulizers, syringes, gaskets, battery packs, electrical firmware and pharmaceutical-grade nicotine liquid, Danek—who had recently sold his stake in a vaporizer company—took everything apart and hacked together a functional prototype.
It wasn’t pretty, but it worked. The first device had a “Frankenstein look,” says the 39-year-old Danek. “I used a syringe as a liquid vessel and there were a lot of external wires because I’m not good at soldering.”
Danek brought the prototype to Greg Smith, founder of Evolution Venture Capital in New York, and he was intrigued enough to cut Danek a check along with San Francisco-based hedge fund Poseidon for $500,000—and Qnovia was born.
The company, which is based in Virginia, has since raised $35 million (from investors that include Blue Ledge Capital, DG Ventures and Vice Ventures) at an estimated $350 million valuation. Now Qnovia is hoping to become the newest player in the $3 billion (global annual sales) nicotine replacement therapy market—but can’t start selling its device in the U.S. (or booking revenue) until it clears the Food and Drug Administration.
Qnovia was approved for an investigational new drug application by the regulator in October and plans to start human clinical trials before the end of the year. If it gets FDA approval, it will become the first federally approved prescription treatment for smoking cessation on the market in nearly two decades. (The last one was Chantix, a blockbuster pill containing varenicline and made by Pfizer, in 2006. Chantix’s patent expired in 2020.)
The big hook for Danek’s product, the RespiRx, is that it does not use combustion (like cigarettes) or heat (like vaporizers), to aerosolize nicotine liquid. (Heat creates carcinogenic byproducts, which are then inhaled along with nicotine. Any cessation method involving heating nicotine would almost certainly be a nonstarter at the FDA.) Rather, Danek’s device is a vibrating mesh nebulizer, which uses a circular disc that moves 150,000 times per second to wick pharmaceutical-grade nicotine liquid into an inhalable vapor.
“Where else in medicine is the standard of care from 20 years ago good enough?”
The task of bringing the RespiRx to market falls to Brian Quigley, Qnovia’s CEO, who formerly led Altria’s smokeless products division (Danek now serves as chief technology officer). Quigley says with 28 million American cigarette smokers, there is not enough being done in the pharmaceutical industry to address smoking, which remains the leading cause of preventable death and disease in the country—killing 480,000 people a year.
“Where else in medicine is the standard of care from 20 years ago good enough?” asks Quigley. “It just seems kind of shocking that here we are in 2024, and this problem has not been solved.”
Technically the FDA considers RespiRx “a drug device combination product,” meaning that it’s both medical device and a drug. Qnovia is applying through an abbreviated approval process that allows the company to use existing data from previously approved drug devices, like the Nicotrol Inhaler, which was marketed by Pfizer before the company discontinued sales last year. That means the RespiRx’s FDA journey should not be as expensive and difficult as it would be for a completely new medication (average cost $880 million over an average of 10 years, with a 91% failure rate), but it’s not a slam dunk either. Qnovia has been working on the RespiRx for the last six years and has already spent $30 million. Danek estimates the company needs at least another $40 million and up to four more years to get FDA approval. And given that’s coming from the company’s founder, that’s probably the best-case estimate.
David Levy, a retired New Jersey-based physician and current investor who has backed a medical device company that went through the FDA approval process, says that the difficulty of getting through the agency’s drug device pipeline should not be underestimated.
“It is a long freaking haul: you have the basic science that goes into this and then you have to go through the clinical trials on that, and then when you have a new delivery mechanism, you enter the device world,” says Levy, who has not invested in Qnovia. “It is long, it is hard, and it is expensive.”
Plus, the FDA has a strict standard when it comes to evaluating clinical trials for smoking cessation drugs: They are only deemed successful if smokers quit, defined as complete abstinence from cigarettes for at least four weeks. But things might be getting easier. The FDA and the National Institutes of Health recently published a paper outlining that while getting smokers to quit is the gold standard, it might consider therapies that prove “clinically meaningful reductions in smoking.”
“The Center for Drug Evaluation and Research is not just encouraging drug development in this space,” an FDA official said during a public meeting in October to discuss the regulator’s evolving approach to approving smoking cessation therapies, “we are in fact rolling out the red carpet and very strongly supporting it.”
“The goal of this product is not to replicate the nicotine delivery of a cigarette,” says Qnovia CEO Brian Quigley, “because we're not trying to get people to use this forever.”
The design of the RespiRx was inspired by e-cigarettes and vapes but uses medical grade dosing to deliver a precise amount of nicotine every day over a 12-week program. For a pack-a-day smoker, the RespiRx, which uses disposable daily pods and would only be available by prescription, will emit 20 doses—10 puffs per dose—on day one and reduce that amount by a little every subsequent day. On the last day of the program, the patient will only have a few doses before, theoretically, quitting altogether.
“The goal in the development of this product is not to replicate the nicotine delivery of a cigarette, because we're not trying to get people to use this forever,” Quigley says. “This is a step-down therapy.”
Judith Prochaska, a professor at the Department of Medicine at Stanford University, licensed clinical psychologist and former president of public health nonprofit Society for Research on Nicotine and Tobacco, says the arduous FDA approval process for NRTs combined with a constant flow of novel nicotine products from Big Tobacco makes it difficult for companies like Qnovia to be successful. Its far easier to get a new nicotine pouch (such as Zyn) through the FDA’s Center for Tobacco Products than it is to get a cessation therapy through the regulator’s Center for Drug Evaluation and Research. The FDA has authorized 45 new tobacco products over the last decade but has not approved a single new cessation drug since 2006.
“Big picture: we don’t have enough options for people to quit smoking, medication-wise,” Prochaska says. “It has proved to be far more challenging to get therapeutics approved by the FDA than it is to get tobacco products authorized.”
Meanwhile, over-the-counter nicotine replacement therapy products, such as nicotine patches, gums and lozenges, have been on the market for decades. None is particularly effective, with success rates hovering around 10%. (Combining two NRTs, like the patch and gum for breakthrough cravings, or an antidepressant and a lozenge, can bring effectiveness up to 20%.) Chantix has a higher success rate (about 30%) but it comes with worrisome and unpleasant side effects, including violent nightmares and nausea.
Until the RespiRx makes it through clinical trials there is no real way of knowing if Qnovia’s approach will be equally (the FDA standard), more, or less effective. One thing going for it: RespiRx delivers nicotine into the bloodstream very quickly, which for people addicted to the drug is a big deal. Patches, gums and lozenges can take anywhere from a few minutes to half an hour to satiate a craving. That time lag can often be a recipe for a relapse. “Speed matters,” says Quigley. “Suffering is an appropriate word to use when describing what smokers are going through during withdrawal.”
But the fact that the RespiRx involves inhaling nicotine-laced vapor might also work against it. “Whenever you're dealing with a lung delivery system, it can be complicated,” says Neal Benowitz, a professor and physician at University of California San Francisco who is a leading voice in the field of nicotine and tobacco addiction and an advisor to Qnovia. “There are some potential concerns about nicotine in the lungs. There are some mechanisms by which nicotine could produce some pulmonary harm.”
There are, of course, other companies trying to develop new smoking cessation drugs. Achieve Life Sciences, which has been working on its cessation medication for 13 years, is the furthest along with a plant-based drug that binds to the nicotinic receptors in the brain to reduce cravings and make nicotine withdrawal symptoms less intense. In a Phase 3 study, 21% of participants that took the medication for 12 weeks remained tobacco-free six months later, compared to only 4.8% of participants who took the placebo. But the FDA has requested the company conduct an additional year-long safety trial.
Qnovia is currently putting the RespiRx through the less-onerous drug approval process in the United Kingdom, where the device is likely to be on the market as a prescription NRT by 2026. The company says it will then use that revenue to get through the FDA process in the U.S. One thing they aren’t worried about is potential customers.
“If we are wildly successful, there would be no more patients to use our medicine,” says Quigley. “But you have to acknowledge that quitting is hard. That's just the power of the addiction. Some will try and fail and hopefully try again.”