Health Canada Approves DOPTELET (avatrombopag) for Two Indications in Thrombocytopenia

2023-11-07

临床结果上市批准

Sobi North America, the North American affiliate of Swedish Orphan Biovitrum AB (Sobi®), today announced that Health Canada has approved DOPTELET® (avatrombopag), an oral thrombopoietin receptor agonist (TPO-RA), for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment and for the treatment of severe thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo an invasive procedure.

”The current treatment landscape for immune thrombocytopenia in Canada has left certain patients with limited options. With today’s approval of Doptelet, patients now have an effective oral treatment option with no food-type restrictions or need for liver function monitoring,” said Dr. Charles H. Li, MD, FRCPC, Consultant Hematologist at Vancouver General Hospital and Clinical Associate Professor at the University of British Columbia. ”Similarly, individuals with chronic liver disease have a new approach to raise their platelet count and optimize hemostasis before invasive procedures – one that avoids the exposure to, and the expenses associated with blood products, such as blood transfusions.”

In adults, ITP lasting for more than one year is considered chronic.1 Approximately, 9.5 per 100,000 adults in the United States and Western Europe are living with ITP, with the condition being more common among younger adult women than men.1,2

“The approval of Doptelet means that certain people in Canada at increased risk of dangerous internal bleeding due to thrombocytopenia now have an option which, because it is taken with food, may be easier to incorporate into their daily routines,” said Bob McLay, Vice President, General Manager of Sobi Canada. “This treatment provides physicians with a new option for those living with thrombocytopenia – a condition in which the number of platelets that are critical for controlling bleeding is low.”

The Health Canada approval of DOPTELET was supported by data from one Phase 3 trial and two Phase 2 trials in patients with chronic ITP and two international, multicenter, randomized, double-blind, placebo-controlled Phase 3 trials, ADAPT-1 and ADAPT-2, in patients with CLD.3

In the pivotal Phase 3 study, DOPTELET administration resulted in a platelet count of at least 50,000 per µL at day eight of therapy in the majority of patients, with efficacy superior to placebo in maintaining platelet counts in the target range during the six-month treatment period.

Pooled safety data for 128 patients with ITP support the safety and tolerability of DOPTELET.

The most common treatment-emergent adverse events (TEAEs) (those occurring in ≥10% of patients) in the DOPTELET treatment group versus placebo were headache (31%), fatigue (28%), contusion (26%), epistaxis (19%), upper respiratory tract infection (15%), arthralgia (13%), gingival bleeding (13%), petechiae (11%) and nasopharyngitis (10%).3

Chronic Liver Disease: ADAPT-1 and ADAPT-2 trials

In both the ADAPT-1 and ADAPT-2 trials, the proportion of patients not requiring a platelet transfusion or any rescue procedure for bleeding was significantly higher in the two DOPTELET-treated groups (low baseline platelet count and high baseline platelet count) than in the placebo group. Both trials demonstrated a higher proportion of patients who achieved the target platelet count of ≥50,000/µL on the day of procedure (a secondary efficacy endpoint) in both DOPTELET-treated groups versus the placebo-treated groups for both cohorts.3

Additionally, both trials demonstrated a greater mean change in platelet counts from baseline to the day of the procedure (a secondary efficacy endpoint) in both DOPTELET-treated groups versus the placebo-treated groups. A measured increase in platelet counts was observed in both DOPTELET-treated groups over time beginning on Day 4 post-dose, that peaked on Day 10-13, decreased seven days post-procedure, and then returned to near baseline values by Day 35.3

The majority of adverse events were mild to moderate in severity and consistent with what was expected in patients with CLD as supported by data from the placebo treatment group. The most common treatment-emergent adverse events (TEAEs) (those occurring in ≥3% of patients) in the DOPTELET-treated groups (60 mg or 40 mg) versus placebo, across the pooled data from the two trials, were pyrexia (10%), abdominal pain (7%), nausea (7%), headache (6%), fatigue (4%) and edema peripheral (3%)l.3

About immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low numbers of platelets that results in an increased risk of bleeding. Symptoms can be highly variable and include bruising, a rash of small dots that represent small hemorrhages, bleeding from the gums or nose, blood in the urine/stools and debilitating fatigue. It is estimated that up to 100 people per million live with ITP. The disorder is considered chronic when symptoms last more than 12 months.4 Long-term, primary chronic ITP is associated with increased risk of infections, bleeding episodes requiring hospitalization, hematologic malignancies, and mortality. No cure is available, and patients with chronic ITP usually relapse after various treatments and still require treatment to reduce the risk of clinically significant bleeding.

About thrombocytopenia in chronic liver disease

Thrombocytopenia is a common complication in patients with chronic liver disease (CLD), with the extent of thrombocytopenia often worsening with the severity of liver disease. Thrombopoietin (TPO), the principal physiologic regulator of platelet production, is produced primarily in the liver. TPO stimulates the production and differentiation of platelet-producing megakaryocytes in the bone marrow. Damage to the liver in patients with CLD can cause reduced TPO production and consequent decreased platelet production and thrombocytopenia. Patients with CLD who have a platelet count of less than 50,000/µL typically require one to three invasive diagnostic and therapeutic procedures per year. Each of these procedures carries a risk of bleeding. If not effectively treated, thrombocytopenia can lead to serious uncontrolled bleeding, resulting in prolonged hospitalizations and other post-procedure complications.

About DOPTELET (avatrombopag)

DOPTELET is an orally bioavailable, small molecule thrombopoietin receptor agonist (TPO-RA) that stimulates the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in increased production of platelets. DOPTELET does not compete with TPO for binding to the TPO receptor.

About Sobi North America

As the North American affiliate of international biopharmaceutical company Sobi, the Sobi North America team is committed to Sobi’s vision of providing access to innovative treatments that make a significant difference in the lives of individuals with rare diseases. Our product portfolio includes multiple approved treatments focused on immunology, hematology and specialty care. With U.S. headquarters in the Boston area, Canadian headquarters in the Toronto area, and field sales, medical and market access representatives spanning North America, our growing team has a proven track record of commercial excellence. More information is available at https://www.sobi.com/canada or at www.sobi.com.

About Sobi®

Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of hematology, immunology and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia and Australia. In 2022, revenue amounted to SEK 18.8 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube.

1 Lambert MP, Gernsheimer TB. Blood. 2017;129(21):2829-2835.

2 National Organization for Rare Disorders. Rare Disease Database. Immune thrombocytopenia. Accessed June 30, 2020. https://rarediseases.org/rare-diseases/immune-thrombocytopenia

3 DOPTELET® (avatrombopag) - Product Monograph. Stockholm, Sweden: Swedish Orphan Biovitrum AB; 2020.

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