Protagonist Reports Updated Long Term Results from Rusfertide Phase 2 REVIVE Study at the EHA2024 Congress Showing Durable Hematocrit Control

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Protagonist Therapeutics presented updated long-term follow-up results from the Phase 2 REVIVE study of rusfertide at the EHA2024 Congress. The study shows that rusfertide provides durable control of hematocrit levels below 45% for up to 3 years in patients with polycythemia vera. Additionally, it reduced the need for phlebotomies and normalized serum ferritin levels without new safety concerns. As of April 9, 2024, 81% of patients remain on treatment, with many transitioning to the THRIVE study for an additional two years. The study reports a stable safety profile, despite a small increase in localized, early-stage skin cancer cases among high-risk patients.

Positive

• Durable hematocrit control below 45% for up to 3 years.
• Decreased phlebotomy requirement from 8.7 to 0.43 per year.
• Normalization of serum ferritin levels.
• Stable mean leukocyte counts throughout the study.
• No new safety signals observed.
• 81% patient retention in the study as of April 9, 2024.
• Patients can transition to THRIVE study for an additional 2 years of treatment.
• Favorable safety profile with majority of adverse events being mild injection site reactions.

Negative

• 11 patients (15.7%) diagnosed with malignancies during the study.
• 9 out of 70 patients (12.9%) diagnosed with skin cancer.
• Asymptomatic increase in platelet counts observed initially.
• Potential concerns regarding long-term safety due to malignancies, despite being localized and early-stage.

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Long term follow-up from REVIVE Phase 2 study up to 3 years shows durable hematocrit (Hct) control (< 45%), decreased phlebotomy use, long-term tolerability, and no new safety signals in patients with polycythemia vera

Patients receiving rusfertide in the open-label extension of the REVIVE study are eligible to roll over to the THRIVE study for an additional 2 years of treatment

NEWARK, CA / ACCESSWIRE / June 14, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced details from two abstracts at the European Hematology Association 2024 Congress, including an oral presentation with long-term follow-up data from the Phase 2 REVIVE study with rusfertide, a mimetic of the natural hormone hepcidin with potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. Copies of the presentations will be available on the Events and Presentations section of the Protagonist website.

Kristen M. Pettit, M.D., Clinical Associate Professor at University of Michigan Health presented the long-term follow-up data from patients in REVIVE who continued into the open label extension (OLE). The Phase 2 trial consisted of 3 parts including 70 patients in the dose-finding Part 1 (28 weeks), 59 patients in the placebo-controlled, randomized withdrawal Part 2 (13 weeks), and 58 patients in the Part 3 OLE (52 weeks). The THRIVE study provides OLE for an additional two years of treatment to patients who have completed Part 3 OLE of the Phase 2 REVIVE study. As of April 9, 2024 (data cut-off for the EHA presentation), 47 patients (81.0%) remain on rusfertide, with 48 patients treated for two or more years and 10 patients treated for three or more years. Of the 58 patients who entered the REVIVE Part 3 OLE, the median duration of therapy is 124.3 weeks as of the April 9, 2024 data cut-off, and 24 patients have rolled over to the THRIVE study for up to two additional years of rusfertide treatment.

"These long-term REVIVE data continue to showcase the positive clinical impact that rusfertide has on PV patients," noted Dr. Kristen M. Pettit. "With up to three years of data showing strong and lasting improvements in hematocrit as well as previous evidence of symptom improvement, rusfertide continues to demonstrate its potential as an important future treatment option for patients with polycythemia vera."

The updated long-term data showed that rusfertide when added to therapeutic phlebotomy with or without cytoreductive therapy resulted in:

• Long term durable control of hematocrit below the 45% threshold for up to 3 years
• Decreased phlebotomy use, from a rate of 8.7 per year before study entry to 0.43 per year in Part 3 of REVIVE, which remained consistent with the rate of 0.36 per year observed for patients randomized to rusfertide in Part 2 of REVIVE
• Decreased red blood cell counts and continued improvement and normalization of serum ferritin levels
• Mean leukocyte counts remained stable throughout the study; an asymptomatic increase in platelets was observed with initiation of rusfertide treatment but stabilized over time
• No new safety signals with the majority of adverse events being Grade 1-2 injection site reactions or adverse events consistent with the comorbidities commonly associated with polycythemia vera

In REVIVE, 19 of 70 patients (27.1%) had a history of cancer prior to enrolling in the study. Among these, 10 (14.3%) had a history of skin cancer. As of April 9, 2024, there are 11 patients diagnosed with malignancies while on study (11/70; 15.7%), including 9 with skin cancer (9/70; 12.9%). All cancers occurred in patients with risk factors such as a prior history of cancer, previous cytoreductive therapy, pre-existing skin lesions that were not biopsied or photosensitive skin. All skin cancers were localized, early stage (in situ or stage 1) and all patients remained on rusfertide after the skin lesions were excised.

"The long-term open label rusfertide data from REVIVE study continue to show a durable positive effect on PV symptomology and other benefits including iron deficiency as well as a solid safety profile. Patients completing the 3-year open-label extension can roll over to the THRIVE open-label study for an additional 2-years providing efficacy and safety for a total of up to 5.8 years of rusfertide treatment," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. "We are very pleased with the continued favorable safety profile and look forward to the top-line data for the VERIFY Phase 3 study's 32-week primary efficacy endpoint by the end of the first quarter of 2025."

A separate abstract accepted for publication only was titled "Absence of QTC Prolongation with Rusfertide, a Hepcidin Mimetic for the Treatment of Polycythemia Vera: A Thorough QT/QTC Study in Healthy Subjects." In this study, 60 healthy subjects were randomized to receive single doses of subcutaneous rusfertide (90mg), matching placebo, or oral moxifloxacin (400mg).Rusfertide was generally well tolerated and did not result in a clinically relevant prolongation of the QTcF interval.

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities (NCEs) rusfertide and JNJ-2113 (formerly PN-235) in advanced stages of clinical development, both derived from the Company's proprietary technology platform. Protagonist and JNJ scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's Interleukin-23 receptor (IL-23R) collaboration with JNJ and followed it through IND-enabling pre-clinical and Phase 1 studies, with JNJ assuming responsibility for further clinical development. Rusfertide, a mimetic of the natural hormone hepcidin, is the Company's lead drug candidate currently in a global Phase 3 development program. The randomized portion of the Phase 2 REVIVE study was unblinded, showing positive results and is now complete, with an open-label extension underway. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Rusfertide will be co-developed and co-commercialized with Takeda pursuant to a worldwide collaboration and license agreement with Takeda entered into in January 2024 and became effective in March 2024.

More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at www.protagonist-inc.com.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of rusfertide. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreement with Janssen, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.

Investor Relations Contact
Corey Davis, Ph.D.
LifeSci Advisors
+1 212 915 2577
cdavis@lifesciadvisors.com

Media Relations Contact

Virginia Amann
ENTENTE Network of Companies
virginiaamann@ententeinc.com
+1 833 500 0061

SOURCE: Protagonist Therapeutics, Inc.

View the original press release on accesswire.com

FAQ

What were the key findings from the Phase 2 REVIVE study of rusfertide?

The study found long-term durable control of hematocrit levels below 45%, reduced phlebotomy use, and improved serum ferritin levels without new safety signals.

How long did patients receive treatment in the REVIVE study?

Patients received treatment for up to 3 years, with some continuing into the THRIVE study for an additional 2 years.

What is the significance of the THRIVE study for rusfertide?

The THRIVE study provides an additional 2 years of treatment for patients who completed the REVIVE study, allowing for up to 5.8 years of total treatment.

Were there any safety concerns reported in the rusfertide study?

No new safety signals were reported; however, 11 patients were diagnosed with malignancies, including 9 with skin cancer, all of which were early stage and localized.

How did rusfertide affect the need for phlebotomies in patients with polycythemia vera?

Rusfertide significantly reduced the need for phlebotomies from 8.7 per year before the study to 0.43 per year in Part 3 of the REVIVE study.