Needle-free epinephrine is a must have for the allergic group as it’ll get rid of the delay in administration brought on by worry of the needle and result in higher outcomes.
ARS Pharma had already labored by way of all the small print of approval of their neffy epinephrine nasal spray with the FDA when on the eleventh hour, the company immediately determined it wanted yet another research, a research it required of no different nasal utilized treatment: repeat dosing of neffy in contrast with intramuscular injection. That research has now been accomplished.
The research enrolled 43 sufferers with seasonal allergic rhinitis who examined constructive with a Whole Nasal Symptom Rating (TNSS) of ≥5 out of 12 and a congestion rating of ≥2 out of three throughout the screening nasal allergen problem (NAC). All sufferers have been dosed with epinephrine inside quarter-hour of induction of the NAC throughout the peak impact, with out permitting time for nasal signs to subside. A second dose of epinephrine was given to sufferers 10 minutes after the primary dose per FDA labeling of epinephrine merchandise.
Based mostly on the corporate’s evaluation of the info, ARS Pharma believes these outcomes ought to assist submitting their response to the FDA and subsequent company approval.
The corporate intends to file its response to the FDA’s Full Response Letter (CRL) for neffy early within the second quarter of 2024, with an anticipated approval (PDUFA) motion date six months from submitting, adopted by potential US launch of neffy within the second half of 2024.
ARS Pharma additionally intends to submit this repeat dose research information to the European Medicines Company (EMA) to tell its Committee for Medicinal Merchandise for Human Use (CHMP) Opinion resolution anticipated by mid-2024.
We at SnackSafely.com urge the FDA to reply shortly following receipt of the CRL to approve neffy in order that it will possibly start saving lives and enhancing outcomes.
Right here follows the ARS press launch in its entirety.
ARS Pharma Publicizes Favorable Topline Outcomes from Repeat Dosing Examine of neffy® (Epinephrine Nasal Spray) Below Nasal Allergen Problem Situations, Readies Knowledge for Response to FDA’s Full Response Letter
February 20, 2024
Repeat doses of neffy below nasal allergen problem reveal a pharmacokinetic profile higher than or much like injection, and a pharmacodynamic profile higher than injection
Firm believes completion of repeat dosing research and nitrosamine assessments tackle the deficiencies recognized within the U.S. Meals and Drug Administration (FDA)’s Full Response Letter (CRL)
NDA on observe to answer CRL early within the second quarter of 2024 adopted by an anticipated six-month evaluation interval
SAN DIEGO, Feb. 20, 2024 (GLOBE NEWSWIRE) — ARS Prescribed drugs, Inc. (NASDAQ: SPRY), a biopharmaceutical firm devoted to empowering at-risk sufferers and caregivers to higher shield sufferers from extreme allergic reactions that would result in anaphylaxis, at the moment introduced topline outcomes from its scientific research evaluating repeat doses of neffy (epinephrine nasal spray) to repeat doses of epinephrine intramuscular (IM) injection, as requested by the FDA with and with out nasal allergen problem (NAC) situations.
“We’re very happy with the topline outcomes from our repeat dose research of neffy below nasal allergen problem situations, which we consider will tackle FDA’s requests of their Full Response Letter and assist the approval of neffy for the therapy of Kind I allergy symptoms, together with anaphylaxis,” stated Richard Lowenthal, Co-Founder, President and CEO of ARS Pharma. “The research goal was to check twice dosing with epinephrine injection and twice dosing with neffy below regular situations and after nasal allergen problem. The outcomes present that the neffy pharmacokinetic and pharmacodynamic profile is bigger than or much like intramuscular injection, the comparator FDA requested for this research. Specifically, repeat dosing in the identical nostril was higher in publicity than dosing as soon as in every nostril and higher than injection on each PK exposures and PD response in any respect time factors, which can assist inform labeling and directions to be used. With these outcomes, we’re finishing the mandatory work to submit our response to FDA within the subsequent couple of months. We stay up for working with the Company in our efforts to make neffy out there to sufferers as quickly as potential.”
Based mostly on the corporate’s evaluation of the info, we consider these outcomes ought to assist submitting our response to the FDA’s CRL. The repeat dose research below NAC situations was designed with the FDA to deal with the Company’s excellent questions concerning neffy as described within the Full Response Letter (CRL) from September 2023. FDA didn’t present steerage on a prespecified set of endpoints, however the information are anticipated to be informative to labeling if a second dose of neffy is required.
ARS Pharma additionally accomplished the nitrosamine testing requested within the CRL per FDA’s draft steerage issued in August 2023, with no measurable ranges of nitrosamines detected.
Beforehand reported information with a single dose of neffy below NAC situations confirmed accelerated absorption of neffy with exposures greater than IM injection throughout the early time interval when scientific response to epinephrine is anticipated.
“When a extreme, life-threatening allergic response happens, it’s essential to administer epinephrine as quickly as potential. Based mostly on the only dose NAC information, my allergy colleagues and myself already believed that neffy could be efficient below NAC situations. FDA requested what would occur if NAC situations occurred throughout the 10% of anaphylaxis occasions that require a repeat dose of epinephrine,” says Thomas B. Casale, M.D., Professor of Drugs and Pediatrics and Chief of Translational Analysis in Allergy/Immunology on the College of South Florida in Tampa. “This research solutions this query – exposures with repeat doses of neffy below NAC are at the least pretty much as good as repeat doses of injection, and dosing in the identical nostril is bigger than injection. I consider the sturdy pharmacodynamic impact noticed with repeat dosing in the identical nostril or reverse nostrils in comparison with injection throughout nasal allergen problem reveals that neffy might be at the least as efficient as injection in reversing anaphylaxis signs, even throughout sometimes noticed rhinitis of word. Along with the 100% response fee lately reported for neffy in treating pediatric oral meals challenge-induced anaphylaxis, I consider this repeat dose NAC information gives additional scientific proof that neffy is efficient below all related scientific situations, and, if authorised, helps its potential to offer an efficient needle-free choice for extreme allergy sufferers and their households.”
ARS Pharma intends to submit this repeat dose NAC research information to the FDA as a part of its response to the CRL early within the second quarter of 2024.
“The security and well being of extreme allergy sufferers is our shared precedence. The neffy repeat dose NAC research ought to tackle the theoretical query FDA recognized within the small subset of allergy sufferers who expertise rhinitis and will require a second dose of epinephrine,” says Sung Poblete, PhD, RN, CEO of FARE. “We’re gratified that these information assist to offer a whole image of neffy use in the actual world, and hopefully will resolve FDA’s said residual uncertainty. Now, practically a 12 months after the FDA Advisory Committee voted for its approval with none extra research, we urge the FDA to maneuver shortly to approve neffy and supply our group with a long-awaited, needle-free epinephrine therapy choice. Allergy sufferers and their households are ready.”
neffy Repeat Dosing Examine Design
The randomized, crossover pharmacokinetic (PK) and pharmacodynamic (PD) research enrolled 43 sufferers with seasonal allergic rhinitis who examined constructive with a Whole Nasal Symptom Rating (TNSS) of ≥5 out of 12 and a congestion rating of ≥2 out of three throughout the screening NAC. NAC entails spraying purified antigen straight onto the nasal mucosa – a ‘worst-case’ experimental situation in distinction to real-world nasal situations resembling higher respiratory tract infections or acute allergic rhinitis from pure causes. All sufferers have been dosed with epinephrine inside quarter-hour of induction of the NAC throughout the peak impact, with out permitting time for nasal signs to subside. A second dose of epinephrine was given to sufferers 10 minutes after the primary dose per FDA labeling of epinephrine merchandise.
FDA explicitly requested that ARS Pharma embrace intramuscular (IM) epinephrine given through guide syringe because the comparator on this research, as IM is the reference-listed drug and historic foundation for efficacy of all different epinephrine merchandise. Meta-analyses (Patel et al, JACI 2021) analyzing over 30,000 anaphylaxis occasions reveal that about 90% of occasions reply to a single dose of epinephrine injection no matter the supply gadget, regardless of important variations in PK.
PK/PD Examine Outcomes
Knowledge from the corporate’s major evaluation of the finished research confirmed that responses on pharmacodynamic (PD) surrogate markers for efficacy in anaphylaxis, resembling systolic blood stress and coronary heart fee, correlated effectively with pharmacokinetic (PK) exposures and have been constantly greater for repeat doses of neffy, no matter dosing in the identical nostril (R/R) or reverse nostrils (R/L), in comparison with repeat doses of IM injection. Dosing in the identical nostril (R/R) resulted in greater PD than injection in any respect time factors measured, whereas dosing within the reverse nostril (R/L) was greater than injection till the 40 to 60 minute time factors, after which PD was indistinguishable from injection.
In step with prior research, important responses on these PD surrogate markers of efficacy with neffy have been noticed even at one minute after dosing. The PD responses reveal that the epinephrine exposures achieved with repeat doses of neffy (R/R or R/L) absolutely activate the receptors concerned in reversing anaphylaxis signs.
Determine 1: Imply Change from Baseline in Systolic Blood Strain (mm Hg)
Determine 2: Imply Change from Baseline in Coronary heart Fee (bpm)
Determine 3: Imply Epinephrine Plasma Concentrations (pg/mL)
The scientific information additionally demonstrated that imply epinephrine concentrations following repeat doses of two mg neffy in the identical nostril (R/R) have been numerically greater than repeat doses of 0.3 mg injection in any respect time factors by way of at the least 240 minutes below NAC situations.
Imply epinephrine concentrations of two mg neffy within the reverse nostril (R/L) have been additionally numerically greater than repeat doses of 0.3 mg injection for roughly half-hour, which is longer than the time interval when scientific response could be anticipated to be noticed after dosing epinephrine (i.e., inside 10 minutes).
The PK profile of repeat doses of neffy throughout regular nasal situations was proven in prior research to be extremely much like repeat doses of EpiPen, which serves because the higher bracket for exposures established to be protected. On this research, the PK profile of repeat doses of neffy in the identical nostril (R/R) throughout nasal allergen problem was extremely much like repeat doses of neffy throughout regular nasal situations, and subsequently additionally within the vary of exposures established to be protected.
Different ARS Pharma scientific research have evaluated neffy PK/PD in individuals with the identical TNSS and congestion severity scores because the experimental NAC research, however with nasal signs resulting from real-world situations resembling higher respiratory tract infections or acute allergic rhinitis from pure causes. These different research confirmed no significant distinction on PK/PD in comparison with dosing neffy below regular nasal situations.
Repeat doses of neffy have been thought-about protected and well-tolerated. All opposed occasions have been delicate and proceed to be per these noticed in prior research of neffy throughout greater than 700 topics. There have been no critical opposed occasions.
Regulatory Standing of neffy
Further discussions with FDA subsequent to its issuance of the CRL confirmed that the brand new information are anticipated to be informative to labeling of administering a second dose of neffy. In Might 2023, the FDA Advisory Committee (PADAC), decided a favorable benefit-risk profile of neffy (16:6 for adults and 17:5 for youngsters). No PADAC member requested a repeat dose research throughout allergen-induced allergic rhinitis. As well as, a number of PADAC members highlighted the favorable profile of neffy in our single dose NAC research.
ARS Pharma intends to file its response to the FDA’s CRL for neffy early within the second quarter of 2024, with an anticipated PDUFA motion date six months from submitting, adopted by potential U.S. launch of neffy within the second half of 2024. ARS Pharma additionally intends to submit this repeat dose research information to the European Medicines Company (EMA) to tell its Committee for Medicinal Merchandise for Human Use (CHMP) Opinion resolution anticipated by mid-2024.
About Kind I Allergic Reactions together with Anaphylaxis
Kind I extreme allergic reactions are critical and doubtlessly life-threatening occasions that may happen inside minutes of publicity to an allergen and require speedy therapy with epinephrine, the one FDA-approved treatment for these reactions. Whereas epinephrine autoinjectors have been proven to be extremely efficient, there are effectively printed limitations that lead to many sufferers and caregivers delaying or not administering therapy in an emergency state of affairs. These limitations embrace worry of the needle, lack of portability, needle-related security considerations, lack of reliability, and complexity of the gadgets. There are roughly 40 million individuals in the US who expertise Kind I extreme allergic reactions. Of these, solely 3.3 million presently have an energetic epinephrine autoinjector prescription, and of these, solely half constantly carry their prescribed autoinjector. Even when sufferers or caregivers carry an autoinjector, greater than half both delay or don’t administer the gadget when wanted in an emergency.
About ARS Prescribed drugs, Inc.
ARS Pharma is a biopharmaceutical firm devoted to empowering at-risk sufferers and caregivers to higher shield themselves from extreme allergic reactions that would result in anaphylaxis. The Firm is creating neffy® (beforehand known as ARS-1), an intranasal epinephrine product in scientific improvement for sufferers and their caregivers with Kind I allergic reactions together with meals, drugs and bug bites that would result in life-threatening anaphylaxis. For extra data, go to www.ars-pharma.com.
Ahead-Wanting Statements
Statements on this press launch that aren’t purely historic in nature are “forward-looking statements” throughout the that means of the Personal Securities Litigation Reform Act of 1995. These statements embrace, however are usually not restricted to ARS Pharma’s perception that the outcomes of the repeat dosing research will assist the submitting of the NDA; the timing for the deliberate NDA submitting; the estimated evaluation time of the NDA; the potential approval of neffy; the timing for the potential U.S. launch of neffy, if authorised; the timing for an anticipated evaluation resolution from CHMP; ; and different statements that aren’t historic truth. As a result of such statements are topic to dangers and uncertainties, precise outcomes could differ materially from these expressed or implied by such forward-looking statements. Phrases resembling “anticipate,” “consider,” “plans,” “expects,” “intend,” “will,” “potential” and related expressions are meant to determine forward-looking statements. These forward-looking statements are primarily based upon ARS Pharma’s present expectations and contain assumptions which will by no means materialize or could show to be incorrect. Precise outcomes and the timing of occasions might differ materially from these anticipated in such forward-looking statements because of numerous dangers and uncertainties, which embrace, with out limitation, FDA didn’t present steerage on a prespecified set of endpoints for the repeat dosing research; FDA could not full its evaluation of the deliberate NDA throughout the anticipated six-month timeframe; the outcomes of the repeat dosing research could not assist the approval of neffy; potential security and different problems from neffy; the labelling for neffy, if authorised; the scope, progress and growth of creating and commercializing neffy; the scale and progress of the market therefor and the speed and diploma of market acceptance thereof vis-à-vis intramuscular injectable merchandise; ARS Pharma’s skill to guard its mental property place; and the influence of presidency legal guidelines and laws. Further dangers and uncertainties that would trigger precise outcomes and outcomes to vary materially from these contemplated by the forward-looking statements are included below the caption “Threat Elements” in ARS Pharma’s Quarterly Report on Type 10-Q for the quarter ended September 30, 2023, filed with the Securities and Change Fee on November 9, 2023. This doc will also be accessed on ARS Pharma’s net web page at ir.ars-pharma.com by clicking on the hyperlink “Financials & Filings.”
The forward-looking statements included on this press launch are made solely as of the date hereof. ARS Pharma assumes no obligation and doesn’t intend to replace these forward-looking statements, besides as required by regulation.
ARS Media Contact:
Laura O’Neill
Laura.oneill@finnpartners.com
ARS Investor Contact:
Justin Chakma
ARS Prescribed drugs
justinc@ars-pharma.com
