Centessa Pharmaceuticals Announces Significant Positive Data from a Proof of Concept Study of SerpinPC in Patients With Severe Hemophilia A and B Not on Prophylaxis | Proteins and Peptides
Centessa Pharmaceuticals Announces Positive First Data from SerpinPC Proof of Concept Study in Patients with Severe Hemophilia A and B Not on Prophylaxis
Category: Proteins and Peptides
Posted on Thursday, September 09, 2021 18:56
~ 88% reduction in median annualized bleeding rate (ABR) for all bleeds and 94% reduction in median ABR for spontaneous joint bleeds at the highest dose tested ~
~ SerpinPC well tolerated ~
~ The company has started planning for a global registration program ~
CAMBRIDGE, MA, USA and LONDON, UK I September 09, 2021 I Centessa Pharmaceuticals plc (“Company”) (Nasdaq: CNTA), together with its subsidiary ApcinteX Limited (“ApcinteX”), today announced the first positive results of the Phase 2a portion of AP-0101, the portion of repeated six-month dose of its first human proof of concept study evaluating SerpinPC in patients with severe hemophilia A and B.
AP-0101 is a Phase 1 / 2a proof-of-concept study evaluating SerpinPC, an activated protein C inhibitor (“APC”), in 23 male subjects with severe hemophilia A or B who were not on prophylaxis .1 The Phase 2a part of the study evaluated the safety, tolerability and pharmacokinetics in three dose cohorts (0.3 mg / kg, 0.6 mg / kg and 1.2 mg / kg) of SerpinPC administered in subcutaneous injection (SC) every 4 weeks over a 24-week period (6 total doses). Reduction in annualized bleeding rates (ABRs) was an exploratory outcome. Although eligible, none of the patients in the study had inhibitors.
SerpinPC was well tolerated. As previously disclosed, a subject with a history of skin disorders discontinued treatment with SerpinPC due to an injection site reaction. No other adverse events related to SerpinPC have been recorded. No sustained elevation of D-dimer, a sensitive measure of excessive thrombin generation, was reported throughout the 24-week study. Two subjects had anti-drug antibodies and remained on treatment with no apparent impact on ABRs.
In the highest dose cohort, SerpinPC reduced the RBA of all self-reported bleeds by 88% during the last 12 weeks of treatment (predefined primary assessment period) compared to the RBA of all self-reported bleeds. Bleeding measured prospectively during the pre-exposure observation period. In the highest dose cohort, five of eight subjects experienced no or no bleeding during the pre-defined 12 week primary assessment period. Self-reported spontaneous joint bleeding ABR was reduced by 94% in the highest dose cohort. Reductions in ABR were similar between patients with hemophilia A or hemophilia B.
|Exploratory efficacy endpoints||0.3 mg / kg
n = 7
|0.6 mg / kg
n = 7
|1.2 mg / kg
n = 8
|All ABR bleeding (median percentage change)||-80%
p = 0.016
p = 0.031
p = 0.016
|ABR spontaneous joint bleeding (median percentage change)||-76%
p = 0.016
p = 0.031
p = 0.023
|The above analyzes compared the last 12 weeks of treatment (pre-specified primary assessment period) to
baseline measurements before exposure. Bleeding events were self-reported.
The p-values shown are based on small numbers and are exploratory in nature.
The median target joint count (joint with> 3 bleeds over a 6 month period) was reduced to zero at the end of the study from a pre-exposure baseline of 2.5. All subjects had target joints at the start of the study and 15 subjects had no target joints at the end of the study.
The 22 patients who completed the Phase 2a portion of the study elected to enroll in the 48-week open-label extension (“OLE”) portion of the study in which a single flat subcutaneous dose 60 mg of SerpinPC will be administered every 4 weeks. over 48 weeks (13 doses in total). Centessa plans to publish the results of the OLE portion of this study in the second half of 2022.
“The convincing reduction in bleeding and continued tolerance that we have seen in patients with hemophilia A and hemophilia B in this proof-of-concept study is very encouraging, and we look forward to bringing SerpinPC into a plan to global development aimed at pursuing one or more registrations. We see a wide utility of SerpinPC in the hemophilia landscape and will seek the fastest route to bring this potential subcutaneous treatment to hemophilia patients, ”said Antoine Yver, MD, M.Sc., medical director of Centessa Pharmaceuticals.
“The results of this Phase 2a study of SerpinPC continue to show an excellent safety profile for this molecule, and the exploratory efficacy results observed in this study in patients with severe hemophilia A and B are also very promising. A safe subcutaneous prophylaxis option for patients with hemophilia A and B would be an important addition to our treatment choices, ”said David Lillicrap, MD, professor of pathology and molecular medicine at Queen’s University, at Kingston, Ontario, Canada and previously Member of the Federation of Hemophilia Advisory Board.
¹ Clinicaltrials.gov ID: NCT04073498 (https://clinicaltrials.gov/ct2/show/NCT04073498)
Conference call and webcast
Centessa Pharmaceuticals will host a webcast and conference call today, September 9, 2021, at 8:30 a.m. EDT to discuss key data from the proof-of-concept trial. To access the audio webcast with slides, please visit the “Events and Publications” page in the Investors and Media section of the Company’s website at https://investors.centessa.com/events-presentations. The call can also be accessed by dialing (855) 493-3565 (national) or (929) 517-9002 (international) with conference ID 8459296. An archive of today’s webcast will be available on the company’s website.
About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc aims to bring impactful new drugs to patients by combining the strengths of an asset-centric model with the advantages of scale and diversification typical of large R&D organizations. The asset-centric model refers to a highly specialized and unique company led by a team of well-recognized subject matter experts. The programs of Centessa’s asset-centric companies range from discovery to late-stage development and include various therapeutic areas such as oncology, hematology, immunology / inflammation, neuroscience, hepatology , pulmonology and nephrology. For more information, visit www.centessa.com.
About ApcinteX Limited
ApcinteX Limited is focused on the development of SerpinPC for the treatment of hemophilia A and hemophilia B. Hemophilia is a rare bleeding disorder that is caused by a deficit in thrombin generation during vascular injury.
SerpinPC, a biologic based on the serpin family of proteins, is designed to help generate more thrombin by inhibiting activated protein C (APC), thereby rebalancing coagulation in patients with hemophilia. SerpinPC has the potential to treat all types of hemophilia, regardless of severity or inhibitor status, and may also prevent bleeding associated with other bleeding disorders.
AP-0101 is an ongoing, open-label Phase 1 / 2a clinical trial to investigate the safety, tolerability and pharmacokinetics of intravenous and subcutaneous doses of SerpinPC in healthy male volunteers and men with severe hemophilia (https : //clinicaltrials.gov/ct2 / show / NCT04073498).
About hemophilia A (HA) and hemophilia B (HB)
HA and HB are X-linked genetic disorders affecting one in 5,000 and one in 20,000 live male births, respectively, resulting in spontaneous internal bleeding that can be life threatening. Over 70% of bleeding occurs in the joints (hemarthrosis) causing chronic joint damage (arthropathy) with musculoskeletal destruction. The bleeding associated with these disorders is the result of a defect or deficiency in factor VIII (in the case of HA) or in factor IX (in the case of HB), the two components of the tenasic complex. intrinsic.
Normal blood clotting (hemostasis) is a crucial part of the physiological response to tissue damage. When blood components come into contact with extravascular cells and proteins, platelets accumulate and ultimately lead to the formation of thrombin, the enzyme that causes blood to clot. Prothrombinase activity is required for the rapid and localized production of thrombin necessary for adequate blood coagulation. Prothrombinase is continuously degraded by APC, which is present in the circulation at low concentrations. In the context of deficient intrinsic tenasic activity (hemophilia), the natural anticoagulant activity of circulating APC results in insufficient prothrombinase activity for normal blood coagulation.
THE SOURCE: Centessa Pharma