2022-06-25 | NDAQ:IONS | Press release

Interim Analysis of B-Clear Clinical Study of Bepivirsen Demonstrated End-of-Treatment Virologic Response (VR) in Patients with Chronic Hepatitis B

Phase 3 clinical study evaluating bepirovirsen monotherapy should start in the first half of 2023

GSK to explore potential combination treatments to further reduce global burden of chronic hepatitis B

CARLSBAD, Calif., June 25, 2022 /PRNewswire/ — Ionis Pharmaceuticals, Inc. (Nasdaq: IONS), today announced that GSK has reported positive results from an interim analysis of Phase 2b B-Clear clinical study of bepirovirsen (formerly IONIS-HBVRx), an investigational antisense drug for the treatment of patients with chronic hepatitis B virus (CHB).

The data was presented during a late-breaking oral session at the European Association for the Study of the Liver (EASL) 2022 International Liver Congress™ in London, UK. The final results of the study will be submitted for presentation at a scientific meeting later this year, and for publication in a peer-reviewed journal.

“Chronic hepatitis B represents a significant health challenge for which there is a particular need for new treatments that provide a more lasting solution. Data from the phase 2b The B-Clear study demonstrated the potential of bepirovirsen to provide rapid reductions in hepatitis B surface antigen in patients not on nuke therapy and in those on stable NA therapy. These findings, along with results from previous clinical studies, support GSK’s plan to initiate a Phase 3 clinical study evaluating bepirovirsen,” said Sanjay BhanotMD, Ph.D., Senior Vice President, Chief Medical Officer and Head of Metabolic and Liver Franchise at Ionis.

In the study, 28% of patients on standard therapy, which is a stable nucleoside/nucleotide (NA) analogue, and 29% of patients not on NA therapy, experienced a virologic response (VR) with bepirovirsen 300 mg weekly , after 24 hours. weeks of treatment. Virological response is defined as serum/plasma levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) below the lower limit of quantification. Up to 68% of NA-treated patients and up to 65% of non-NA-treated patients achieved HBsAg

End-of-treatment virological responses have been observed in patients with high or low baseline HBsAg levels who were hepatitis B e antigen (HBeAg) negative or positive and who were or were not receiving NA therapy, which indicates that bepivirsen has the potential to treat large segments of the CHB population. The sustainability of responses is being assessed.

Treatment-related serious adverse events (SAEs) were observed in

Chronic hepatitis B infection is caused by HBV and is a major global health problem, affecting nearly 300 million people worldwide.i, ii

Currently, nucleoside/nucleotide analogues are the recommended first-line treatment for patients with chronic HBV, as they can inhibit viral replication. However, they cannot eliminate the virus and must be taken for life. Bepirovirsen is specifically designed to reduce HBV replication and suppress HBsAg which could potentially lead to functional cure, broadly defined as sustained and undetectable levels of hepatitis B virus DNA and HBsAg in the blood with or without generation of protective antibodies after a finished treatment.

GSK is also exploring combinations of bepirovirsen and other treatment modalities in subsequent trials. Combination treatments could increase functional cure rates in more patients, further reducing the overall disease burden of HCB. Trials include:

  • Phase 2b trial of bepivirsen in sequential combination with pegylated interferon (PegIFN) therapy
  • Phase 2 Trial of Bepirovirsen in Combination with GSK’s Chronic Hepatitis B Targeted Immunotherapy

About Stage B-Clear 2b test

The B-Clear phase 2b The study is investigating the efficacy and safety of a 12 or 24 week course of bepivirsen in people living with HCB on stable NA therapy or not on NA therapy at the start of the study. The primary endpoints are the proportion of patients achieving HBsAg levels below the lower limit of quantification (LLOQ) and HBV DNA levels below the LLOQ maintained for 24 weeks without rescue medication after the end of treatment with bepivirsen.

The study consists of two parallel cohorts, one for patients receiving NA treatment and the other for patients who were not on NA. Patients in each arm were randomized to 1 of 4 treatment arms within each cohort, with treatment administered weekly with or without loading doses (LD) on days 4 and 11:

  • Bepirovirsen 300 mg with LD for 24 weeks;
  • Bepirovirsen 300 mg with LD for 12 weeks then 150 mg for 12 weeks;
  • Bepirovirsen 300 mg with LD for 12 weeks then placebo for 12 weeks;
  • Placebo with LD for 12 weeks then bepirovirsen 300 mg without LD for 12 weeks.

In both cohorts, virological responses were observed at the end of treatment:

  • For patients receiving NA therapy (n=227), 24 weeks of treatment with bepirovirsen 300 mg per week resulted in HBsAg
  • For non-NA patients (n=230), a 24-week course of bepirovirsen 300 mg weekly resulted in HBsAg
  • The sustainability of these responses is being assessed.

About Hepatitis B Virus Infection

Hepatitis B virus infection is a serious health condition that can lead to significant and life-threatening health problems, including cirrhosis, liver failure, and liver cancer. Chronic hepatitis B infection is caused by the hepatitis B virus and is a major global health problem, affecting nearly 300 million people worldwide.I,ii Chronic HBV infection is one of the most common persistent viral infections worldwide. Currently available therapies, although effective in reducing circulating HBV DNA in the blood, do not effectively inhibit HBV antigen production and secretion.

About Bepivirsen

Bepirovirsen (formerly IONIS-HBVRx), also known as GSK3228836, is an investigational Ionis antisense drug designed to reduce the production of viral proteins associated with hepatitis B virus (HBV) infection and replication, including the antigen of surface hepatitis B, which is present in both acute and chronic infections and is associated with poor prognosis in patients with chronic HBV infection. GSK has licensed Ionis bepirovirsen under a collaborative development and licensing agreement.

About Ionis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been the leader in RNA-targeted therapy, opening new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed drugs and a leading late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become a leading, fully integrated biotechnology company.

To learn more about Ionis, visit www.ionispharma.com and follow us on Twitter @ionispharma.

Ionis Forward-Looking Statements

This press release contains forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of Ionis’ technologies, bepirovirsen and other products in development. Any statement describing Ionis’ objectives, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. These statements are subject to certain risks and uncertainties, including those relating to the impact that COVID-19 may have on our business, and including, but not limited to, those relating to our commercial products and pharmaceuticals. our pipeline, and in particular those inherent in the process of discovering, developing and commercializing safe and effective drugs for human therapeutic use, and in the effort to build a business around these drugs. Ionis’ forward-looking statements also involve assumptions which, if they never materialize or prove to be incorrect, could cause its results to differ materially from those expressed or implied by such forward-looking statements.

Although Ionis’ forward-looking statements reflect the good faith judgment of its management, such statements are based solely on facts and factors currently known to Ionis. Accordingly, you are cautioned not to rely on these forward-looking statements. These and other risks relating to Ionis’ programs are described in greater detail in Ionis’ Annual Report on Form 10-K for the fiscal year ended December 31, 2021, and most recent quarterly Form 10-Q filing. , which is filed with the Security and Exchange Commission. Copies of these and other documents are available from the Company.

In this press release, unless the context otherwise requires, “Ionis”, “Company”, “we”, “us” and “our” refer to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc.

I Trepo C, et al. Hepatitis B virus infection. Lancet. 2014 December 6; 384(9959): 2053-63. https://doi.org/10.1016/S0140-6736(14)60220-8

ii World Health Organization, https://www.who.int/news-room/fact-sheets/detail/hepatitis-b

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SOURCEIonis Pharmaceuticals, Inc.

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