Each vonoprazan-based remedy regimens demonstrated superior eradication charges vs. a typical of care proton pump inhibitor (PPI)-based triple remedy New Drug Utility (NDA) submissions focused for This autumn 2021
FLORHAM PARK, N.J., April 29, 2021 (GLOBE NEWSWIRE) — Phathom Prescription drugs, Inc. (Nasdaq: PHAT), a late clinical-stage biopharmaceutical firm centered on creating and commercializing novel therapies for gastrointestinal ailments, introduced in the present day that in PHALCON-HP, its pivotal Section Three scientific trial for the eradication of H. pylori an infection, each vonoprazan-based regimens efficiently met their major endpoints and met all secondary endpoints. The trial studied vonoprazan together with amoxicillin and clarithromycin (“vonoprazan triple remedy”) and vonoprazan together with amoxicillin (“vonoprazan twin remedy”) in comparison with lansoprazole together with amoxicillin and clarithromycin (“lansoprazole triple remedy”). PHALCON-HP is the most important Section Three registration trial ever performed in H. pylori an infection, randomizing 992 sufferers with confirmed H. pylori an infection.
Section Three Topline Outcomes
Main endpoint evaluation
The first endpoints within the PHALCON-HP examine had been non-inferiority of the H. pylori eradication fee for every of vonoprazan triple and twin remedy in comparison with lansoprazole triple remedy. Based mostly on U.S. Meals and Drug Administration (FDA) suggestions, the first endpoint excluded sufferers with amoxicillin or clarithromycin resistant strains of H. pylori.
Each vonoprazan-based regimens efficiently met their major endpoints. Within the modified intent-to-treat (mITT) inhabitants, H. pylori eradication charges had been 84.7% with vonoprazan triple remedy and 78.5% for vonoprazan twin remedy in comparison with 78.8% with lansoprazole triple remedy (p<0.0001 and p=0.0037, respectively, for non-inferiority).
Further efficacy analyses had been performed utilizing the pre-specified per protocol inhabitants, a subset of the mITT inhabitants comprised of sufferers who had been protocol compliant as outlined by FDA draft Steerage for Industry1. Within the per protocol inhabitants, H. pylori eradication charges had been 90.4% with vonoprazan triple remedy and 81.2% with vonoprazan twin remedy in comparison with 82.1% with lansoprazole triple remedy (p<0.0001 and p=0.0077, respectively, for non-inferiority).
Secondary endpoint evaluation
Vonoprazan triple remedy and vonoprazan twin remedy additionally met all secondary endpoints, demonstrating superior eradication charges versus lansoprazole triple remedy in all sufferers and sufferers with clarithromycin resistant strains of H. pylori. Sufferers with clarithromycin resistant strains comprised 20.3% of the PHALCON-HP examine inhabitants.
Vonoprazan triple remedy
The H. pylori eradication fee of vonoprazan triple remedy was superior to that of lansoprazole triple remedy amongst all sufferers in each the mITT inhabitants (80.8% vs. 68.5%; p=0.0001) and the per protocol inhabitants (85.7% vs. 70.0%; p<0.0001).
The H. pylori eradication fee with vonoprazan triple remedy was superior to that of lansoprazole triple remedy within the subset of sufferers with H. pylori strains proof against clarithromycin in each the mITT inhabitants (65.8% vs. 31.9%; p<0.0001) and the per protocol inhabitants (67.2% vs. 29.0%; p<0.0001).
Vonoprazan twin remedy
The H. pylori eradication fee of vonoprazan twin remedy was superior to that of lansoprazole triple remedy amongst all sufferers in each the mITT inhabitants (77.2% vs. 68.5%; p=0.0063) and the per protocol inhabitants (81.1% vs. 70.0%; p=0.0013).
The H. pylori eradication fee of vonoprazan twin remedy was superior to that of lansoprazole triple remedy within the subset of sufferers with H. pylori strains proof against clarithromycin in each the mITT inhabitants (69.6% vs. 31.9%; p<0.0001) and the per protocol inhabitants (79.5% vs. 29.0%; p<0.0001).
“Acid suppression is a key consider addressing shortcomings related to at present accessible H. pylori therapies, particularly in gentle of elevated resistance to antibiotics, together with clarithromycin,” stated Professor William D. Chey, M.D., AGAF, FACG, FACP, Professor of Drugs and Director of the GI Physiology Laboratory on the College of Michigan. “I’m very impressed with the outcomes of PHALCON-HP which display that changing a PPI with vonoprazan in H. pylori remedy regimens has the potential to meaningfully improve eradication charges which were declining over the past 20 years. Additional, the potential to restrict the usage of clarithromycin with a twin remedy routine has the potential to remodel scientific apply.”
Each vonoprazan-based regimens had been usually effectively tolerated with a security profile akin to lansoprazole triple remedy. The commonest antagonistic occasions (>2.0%) reported within the vonoprazan triple remedy, vonoprazan twin remedy, and lansoprazole triple remedy arms, respectively, had been diarrhea (4.0%, 5.2%, and 9.6%), dysgeusia (4.3%, 0.6%, and 6.1%), nausea (1.7%, 1.7% and a pair of.6%), headache (2.6%, 1.4%, 1.4%) and vaginal infections (2.3%, 0.9%, 0.3%). Total charges of discontinuation resulting from antagonistic occasions had been 2.3% for vonoprazan triple therapy-treated sufferers, 0.9% for vonoprazan twin therapy-treated sufferers, and 1.4% for lansoprazole triple therapy-treated sufferers.
Full outcomes from the PHALCON-HP examine might be offered at a future medical assembly and submitted for publication in a peer-reviewed journal.
“We imagine the topline outcomes of our PHALCON-HP examine assist the potential of vonoprazan-based therapies to vary H. pylori remedy,” stated Terrie Curran, Phathom’s President and Chief Government Officer. “There are estimated to be over 200 million folks contaminated with H. pylori in the USA and Europe, and our market analysis amongst sufferers and physicians present antibiotic resistance, coupled with complexity of remedy, as main causes of eradication failure. Based mostly on these outcomes, which additional construct on the strong knowledge beforehand reported from scientific research of vonoprazan-based regimens in Japan, we plan to submit NDAs with the FDA for vonoprazan twin and triple remedy in H. pylori earlier than the top of the yr. Phathom thanks all of the sufferers, physicians, and scientific websites for his or her function within the PHALCON-HP trial and for serving to in our efforts to advance the remedy panorama for the thousands and thousands of sufferers struggling with H. pylori an infection.”
About Helicobacter pylori (H. pylori) an infection
H. pylori is a bacterial pathogen that’s estimated to contaminate over 200 million people in the USA and Europe. Roughly 50% of the world and 36% of the US inhabitants are contaminated with the bacterium.2 In lots of circumstances, H. pylori is acquired in childhood and thru intrafamilial transmission.3 Because of the power irritation induced by H. pylori an infection, contaminated sufferers develop a spread of pathologies together with dyspepsia, peptic ulcer illness, gastric most cancers, and mucosa-associated lymphoid tissue (MALT) lymphoma.4 Research have discovered that roughly 1 in 5 sufferers handled for H. pylori will fail first line remedy when utilizing commonplace clarithromycin triple remedy.2,5
PHALCON-HP was a randomized, multicenter, Section Three trial that enrolled 1046 sufferers of which 992 sufferers with a confirmed H. pylori an infection had been randomized to one among three arms: vonoprazan 20 mg administered twice a day (BID) and amoxicillin 1g administered thrice a day (TID) (n=324); vonoprazan 20 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=338); and lansoprazole 30 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID (n=330). Every remedy routine was administered for 14 days. Diagnoses of an infection and take a look at of remedy had been confirmed by 13C-urea breath take a look at. Further efficacy analyses had been performed utilizing the pre-specified per protocol inhabitants (n=822), a subset of the mITT inhabitants comprised of sufferers who had been protocol compliant.
Vonoprazan is an investigational, oral small molecule potassium-competitive acid blocker (P-CAB). P-CABs are a novel class of medicines that block acid secretion within the abdomen. Vonoprazan has proven the potential to have fast, potent, and sturdy anti-secretory results as a single agent within the remedy of gastroesophageal reflux illness (GERD) and together with antibiotics for the remedy of Helicobacter pylori (H. pylori) an infection. The FDA has awarded Quick Monitor designation to vonoprazan together with each amoxicillin and clarithromycin and with amoxicillin alone for the remedy of H. pylori an infection. Phathom in-licensed the U.S., European, and Canadian rights to vonoprazan from Takeda, which accomplished 19 Section Three trials for vonoprazan and obtained advertising approval in Japan and quite a few different nations in Asia and Latin America.
Phathom Prescription drugs is a biopharmaceutical firm centered on the event and commercialization of novel therapies for gastrointestinal ailments and problems. Phathom has in-licensed the unique rights in the USA, Europe, and Canada to vonoprazan, a novel potassium aggressive acid blocker (P-CAB) in late-stage improvement for the remedy of acid-related problems. For extra details about Phathom, go to the Firm’s web site at or observe the Firm on social media: LinkedIn at and Twitter @PhathomPharma.
Ahead Wanting Statements
Phathom cautions you that statements contained on this press launch concerning issues that aren’t historic details are forward-looking statements. These statements are primarily based on the Firm’s present beliefs and expectations. Such forward-looking statements embrace, however usually are not restricted to, statements concerning the anticipated submission of New Drug Purposes for the eradication of H. pylori an infection; and the potential for vonoprazan-based therapies to meaningfully improve H. pylori eradication charges, restrict the usage of clarithromycin, and deal with shortcomings related to at present accessible therapies. The inclusion of forward-looking statements shouldn’t be thought to be a illustration by Phathom that any of its plans might be achieved. Precise outcomes could differ from these set forth on this press launch because of the dangers and uncertainties inherent in Phathom’s enterprise, together with, with out limitation: reported top-line knowledge is predicated on preliminary evaluation of key efficacy and security knowledge is topic to extra audit and verification procedures that might lead to materials modifications within the closing knowledge; we could expertise delays submitting the NDAs together with within the occasion that the FDA doesn’t agree with the Firm’s interpretation of the info or suggestions from the FDA which may be inconsistent with suggestions obtained at prior conferences with the FDA; Phathom’s dependence on third events in reference to product manufacturing, analysis and preclinical and scientific testing; regulatory developments in the USA and overseas nations; sudden antagonistic unwanted effects or insufficient efficacy of vonoprazan which will restrict its improvement, regulatory approval and/or commercialization, or could lead to recollects or product legal responsibility claims; Phathom’s pending certified infectious illness product (QIDP) requests is probably not granted and beforehand granted QIDP and Quick Monitor designations could also be withdrawn or not truly result in a quicker improvement or regulatory assessment or prolonged exclusivity, and wouldn’t guarantee FDA approval of vonoprazan; Phathom’s potential to acquire and keep mental property safety for vonoprazan; Phathom’s potential to adjust to its license settlement with Takeda; Phathom’s potential to keep up undisrupted enterprise operations because of the ongoing unfold of the COVID-19 coronavirus, together with delaying or in any other case disrupting its scientific trials, manufacturing and provide chain, and different dangers described within the Firm’s prior press releases and the Firm’s filings with the Securities and Trade Fee (SEC), together with underneath the heading “Threat Elements” within the Firm’s Annual Report on Kind 10-Ok and any subsequent filings with the SEC. You’re cautioned to not place undue reliance on these forward-looking statements, which communicate solely as of the date hereof, and Phathom undertakes no obligation to replace such statements to mirror occasions that happen or circumstances that exist after the date hereof. All forward-looking statements are certified of their entirety by this cautionary assertion, which is made underneath the protected harbor provisions of the Personal Securities Litigation Reform Act of 1995.
2 Hooi et al. Gastroenterology. 2017;153:420.
3 Chey et al. Am J Gastroenterol.2017;112:212.
4 Malfertheiner et al. Intestine. 2017;66:6.
5 Alsamman et al. Dig Dis Sci. 2019;64:2893.
Supply: Phathom Prescription drugs, Inc.
Posted: April 2021