US Has Pieces For Solving Policy Puzzle To Spur Spread Of Smoking Cessation Products, Programs

All the pieces needed to accelerate smoking cessation in the US and increase the number of therapeutic products with the indication are in place if the Biden administration is ready to act, says a former tobacco programs chief for the Food and Drug Administration.

The pieces, says Mitch Zeller, include a commitment from the White House to requiring a reduction in nicotine levels allowed in tobacco products and movement by the FDA on finalizing rules prohibiting the use of menthol and other flavors in cigarettes and some cigars.

Other pieces are a nicotine replacement therapy using pulmonary delivery in development by a firm Zeller’s advising on policy and regulatory strategy, Qnovia Inc. and FDA considering changes to its drug and device approval rules so that innovations in NRT technologies have a chance for success and the number of smokers trying to quit will increase. (HBW Insight will publish reporting on these pieces on 14 June.)

In an interview, Zeller pointed out FDA Commissioner Robert Califf and the White House have stated “that more needs to be done broadly for cessation."

While the commissioner has referenced expanding cessation options in multiple public comments, the Biden administration in June 2022 was reported to support requiring reducing nicotine levels in tobacco products.

“Clearly, more needs to be done – products, programs and services. It's not just about FDA and pharmacotherapy. It's every federal agency that could have anything to do with patient policy, to help more smokers quit, should be engaged in some all-of-government approach to this,” said Zeller, who resigned in May 2022 after nine years as FDA Center for Tobacco Products director. (Also see "US HBW Executive Decisions: FDA's Zeller Retires; CHPA, GOED Additions; ACI VP On ITAC3" - HBW Insight, 3 May, 2022.)

Qnovia, a venture-backed firm based in Richmond, VA, expects to have clearance later this year from the FDA Center for Drug Evaluation and Research to begin an investigational new drug trial for its Rx NRT using inhalation to deliver nicotine as rapidly as its delivered by cigarettes and to submit an NDA for the agency’s approval in 2025. (Also see "With FDA Guidance Urging Innovation, Will Novel Smoking Cessation Products Surface In US?" - HBW Insight, 30 Apr, 2023.)

“Here's an opportunity both for industry and for the regulator, because it now looks like there is a way to deliver nicotine into the lungs without having to burn tobacco leaves and inhale the 7,000 chemicals” typically found in cigarettes, said Zeller.

mitch zeller: “every federal agency that could have anything to do with patient policy, to help more smokers quit, should be engaged in some all-of-government approach to this." Source: FDA

The FDA as well as other regulatory and public health agencies should recognize the cause of the need for smoking cessation products when considering allowing marketing of products promoted to help smokers quit, says Zeller, a proponent while CTP director of cross-center collaboration at the FDA on a “continuum of nicotine-delivering products” and for adopting a more harm-reduction focused policy for approving more NRT products. (Also see "FDA Floats Broader Pathway For Nicotine Replacement Therapies" - HBW Insight, 3 Jul, 2013.)

Cigarettes, he said, are “deliberately designed to create and sustain addiction and that will kill half of all of its lonhwg-term users prematurely later in life.”

“Whether it's new and better tools, with FDA being at the table and looking at itself as part of the solution, or a more government-wide approach to cessation, whether it's better reimbursement policies, a greater investment in counseling, and a whole bunch of public education efforts aimed at dispelling misperceptions that the public has about nicotine safety, there's a lot that the can and should be done,” he added.

White House Listens, Supports Limiting Nicotine Levels

With better tools available for smoking cessation, uptake of the products could be accelerated with more smokers willing to try to quit.

“All cigarettes sold in the United States have addictive levels of nicotine,” Zeller said.

He made the same argument to Biden administration officials over the last roughly 15 months of his time as CTP director. He noted, too, that banning menthol and other flavors in cigarettes and cigars would help convince more smokers to attempt to quit.

“If those two things change, then based upon the real world experience of menthol bans in other countries and the clinical trial setting for nicotine reduction, and the dynamic population level modeling that's been done on nicotine reduction, one would expect that amongst the tens of millions of smokers, when those policies go into effect, millions of smokers are going to have a newfound interest in quitting,” Zeller said.

The FDA in April 2022 announced a proposed rule prohibiting menthol as a characterizing flavor in cigarettes and prohibit all characterizing flavors in cigars other than tobacco. The agency’s latest semi-annual regulatory agenda indicated it expected to publish a final rule before the end of 2023.

Zeller said his request to the White House was based on language in the Tobacco Control Act, which authorized the FDA to regulate production and sales of tobacco products including “the power to ban or to limit the allowable level of any ingredients, or compound or constituent or additive in finished products.”

“It sounds like the message that we delivered was received,” he said.

And while he’s had no contact with administration officials since, his sense is that a proposal will come soon for a government-wide programs led by the Department of Health and Human Services.

“I think that it is incumbent upon FDA, HHS and White House leadership to make sure that there is an all-of-government approach to cessation,” he added.

Clinical Trials Guidance Finalized, OTC NRT Innovation On Hold

Movement from the White House is anticipated after the FDA in May finalized its guidance on clinical trials for smoking cessation or related indications with little change from the draft published four years, two commissioners and a stalled novel OTC product proposal ago. (Also see "US Smoking Cessation Clinical Trials Guidance 'Does Not Envision' Flexibility On Indications" - HBW Insight, 30 Apr, 2023.)

The CDER’s guidance reiterated its expectation for multiple clinical trials to demonstrate an investigational NRT product with characteristics different from an approved product, such as route of administration, is effective for smoking cessation or reduction in risk of relapse.

The clinical trials draft guidance was published before the FDA in late 2019 imposed a pause on GSK plc consumer health care business’s proposal to market the first mouth spray NRT in the US with questions about the OTC product’s Drug Facts label. The product, which would to be marketed under the Nicorette brand, already is marketed nonprescription in numerous other countries but isn’t available Rx or OTC in the US. (Also see "GSK’s Proposal For Mouth Spray Nicorette Delayed By FDA Questions On Label" - HBW Insight, 8 Jan, 2020.)

Earlier in 2023, the OTC mouth spray NRT approved in the UK, where Johnson & Johnson has marketing rights, gained an additional indication. The Medicines and Healthcare products Regulatory Agency approved for J&J the use of Nicorette QuickMist Mouthspray as a way for users to give up vaping, marking the world’s NRT indicate for vaping as well as smoking cessation. (Also see "J&J’s Nicorette Becomes World’s First Licensed Vaping And Smoking Cessation Therapy" - HBW Insight, 24 Jan, 2023.)

The GSK business, operating as Haleon plc since its spinout in 2022, has said it planned to make changes the FDA requested in a Complete Response letter. The new drug application GSK submitted was for an oral spray that delivers 1 mg per spray of aqueous buffered nicotine solution for oromucosal use with indications of reducing withdrawal symptoms, including nicotine craving, associated with quitting smoking for consumers 18 and up.