Pfizer’s Hympavzi shows good results in phase 3 BASIS study

Overview

Pfizer Inc. announced positive topline results from the phase 3 BASIS study (NCT03938792) evaluating Hympavzi (marstacimab) for adults and adolescents living with haemophilia A or B with inhibitors. The study met the primary endpoint and key secondary bleeding endpoints demonstrating the superiority of once-weekly subcutaneous Hympavzi in improving key bleeding outcomes compared to on-demand treatment in a patient population where less burdensome treatment approaches are needed.

Inhibitors & haemophilia

• Inhibitors, or antibodies, which neutralize factor replacement therapies and render them ineffective, may develop in people living with haemophilia. 
• Inhibitors can be diagnosed with a blood test. 
• Of the more than 800,000 people in the world living with haemophilia A or haemophilia B, approximately 20% of people with haemophilia A and 3% of people with haemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII (Factor VIII) and FIX (Factor IX) and these therapies no longer prevent or stop bleeding episodes.

Statement from the BASIS Principal Investigator

Patients with inhibitors tend to face frequent complications, and navigating the treatment landscape can introduce complexities and increase disease burden,” said Davide Matino, M.D., M.Sc., BASIS Principal Investigator, Associate Professor of Medicine, McMaster University. 

“The strong bleed reduction with Hympavzi compared to on-demand treatment in the phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options.”

BASIS trial for Hympavzi: outcomes

• The BASIS trial demonstrated that prophylactic treatment with Hympavzi resulted in a statistically significant and clinically relevant reduction in annualized bleeding rate (ABR) of treated bleeds in people living with severe haemophilia A or haemophilia B with inhibitors. 
• Forty-eight people living with haemophilia were treated with Hympavzi during a 12-month period versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in the six-month lead-in period. 
• Hympavzi was superior to on-demand treatment with a 93% reduction in ABR over 12 months (ABR 1.39 vs ABR on-demand 19.78; p < 0.0001). 
• Superiority of Hympavzi was also demonstrated across all bleeding-related secondary endpoints—spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds.
• Hympavzi was generally well-tolerated, consistent with the non-inhibitor cohort of the BASIS study and phase 1/2 results. No deaths or thromboembolic events were reported.

Statement from chief inflammation & immunology officer: Pfizer

These encouraging results demonstrate Hympavzi’s potential to help people living with haemophilia A or B with inhibitors, meeting an important need for patients with antibodies that neutralize most factor-based prophylactic options used to manage bleeding episodes,” said Michael Vincent, M.D., Ph.D., chief inflammation & immunology officer, Pfizer. 

Hympavzi represents Pfizer’s latest contribution in more than 40 years of working to advance haemophilia care, as a generally well-tolerated treatment option that could offer bleed protection with a straightforward, once-weekly subcutaneous administration in a pre-filled pen for patients with inhibitors, if approved in this patient population.”

Pfizer Advances Hympavzi Toward Regulatory Filings for Hemophilia with Inhibitors

• Full Phase 3 data analyses from the inhibitor cohort of the BASIS study are currently ongoing.
• Additional data presentations are planned for upcoming medical meetings.
• Based on these results, Pfizer intends to engage with regulatory authorities to discuss a potential pathway for approval.
• The goal is to initiate regulatory filings for Hympavzi as a treatment for patients living with hemophilia with inhibitors, addressing a critical unmet need in this population.

The Hympavzi: mechanism of action on TFPI

• Discovered by Pfizer scientists, Hympavzi has a mechanism of action that is differentiated from FVIII and FIX replacement treatments. 
• Instead of replacing missing or insufficient clotting factors, Hympavzi is intentionally designed to target tissue factor pathway inhibitor (TFPI), one of the body’s natural mechanisms that inhibits the initiation of blood clotting. 
• By targeting the Kunitz 2 domain of TFPI, Hympavzi may help re-establish balance between bleeding and blood clot formation with the goal of offering a combination of bleed protection, good tolerability, and straightforward administration.

The phase 3 global trial: pivotal BASIS study

• The pivotal BASIS study is a global phase 3, open-label, multicenter study to evaluate the efficacy and safety of Hympavzi in adolescent and adult participants ages 12 to <75 years with severe haemophilia A (defined as FVIII <1%) or moderately severe to severe haemophilia B (defined as FIX activity =2%) with or without inhibitors.
• This cohort included 48 people living with haemophilia with inhibitors who were treated with Hympavzi during a 12-month active treatment period (ATP) versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in a six-month observational period. 
• During the ATP, participants received prophylaxis (a 300 mg subcutaneous loading dose of Hympavzi, followed by 150 mg subcutaneously once weekly) with potential for dose escalation to 300 mg once weekly. 
• An additional three patients in the inhibitor cohort were on routine prophylactic treatment prior to the study and not included in the primary efficacy analysis.
• The primary endpoint- The primary endpoint measures the treated ABR during the 12-month ATP with Hympavzi compared to treated ABR on prior on-demand replacement therapy. 

Approval received for Hympavzi

• Hympavzi has received regulatory approvals in the US and in Europe for eligible patients living with haemophilia A without factor VIII inhibitors, or haemophilia B without factor IX inhibitors. 
• Hympavzi was the first anti-TFPI approved in the US and EU for the treatment of haemophilia A or B and the first haemophilia medicine approved in the US and EU to be administered via a pre-filled, auto-injector pen. 
• For eligible people living with haemophilia B, it is the first once-weekly subcutaneous prophylactic treatment. 
• Hympavzi can offer a subcutaneous treatment option with a once-weekly dosing schedule and minimal preparation required for each individual administration.

Pfizer’s safety and efficacy of Hympavzi

Pfizer is also conducting BASIS KIDS, an open-label study investigating the safety and efficacy of Hympavzi in children 1 to <18 years of age with severe haemophilia A or moderately severe to severe haemophilia B with or without inhibitors.

Information about the genetic condition: Haemophilia

• Haemophilia is a family of rare genetic blood diseases caused by a clotting factor deficiency (FVIII in haemophilia A, FIX in haemophilia B), which prevents normal blood clotting. 
• Haemophilia is diagnosed in early childhood and impacts more than 800,000 people worldwide. 
• The inability of the blood to clot properly can increase the risk of painful bleeding inside the joints, which can cause joint scarring and damage. 
• People living with haemophilia can suffer permanent joint damage following repeated bleeding episodes.

Treatment options & challenges

• For decades, the most common treatment approach for haemophilia A and B has been factor replacement therapy, which replaces the missing clotting factors. 
• Factor replacement therapies increase the amount of clotting factor in the body to levels that improve clotting, resulting in less bleeding. 
• The burden of intravenous infusions is believed to be a barrier to treatment adherence for some people living with haemophilia due in part to inconvenience, time constraints, and poor venous access.

Complications surrounding the present therapies

• Approximately 20% of people with haemophilia A and 3% of people with haemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII and FIX. 
• These patients often have higher treatment burden, including potential complications from bleeding such as hospitalization and death, as well as higher treatment-related costs.

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