- Phase II data demonstrate that rozanolixizumab was well tolerated by patients with primary ITP across all dose groups
- Clinically relevant improvements in platelet count and decrease in immunoglobin G (IgG) levels were observed in all dose groups
- Safety, tolerability and efficacy data support Phase III development of rozanolixizumab for primary ITP
- Rozanolixizumab's subcutaneous route of administration could provide a new treatment option for patients with primary ITP
BRUSSELS, Dec. 10, 2019 /PRNewswire/ -- UCB, a global biopharmaceutical company, today announced positive results from a Phase II study (TP0001; NCT02718716) of its novel, first-in-class subcutaneous (SC, under the skin) monoclonal antibody, rozanolixizumab, in patients with primary immune thrombocytopenia (ITP). The data were presented during an oral presentation today at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.
The Phase II TP0001 study to assess the safety, tolerability and efficacy of rozanolixizumab was designed to explore a multiple dose regimen in order to inform the dosing strategy for further development in ITP. Sixty-six patients received either a single dose (1 x 15 mg/kg or 1 x 20 mg/kg) or multiple doses (5 x 4 mg/kg, 3 x 7 mg/kg, 2 x 10 mg/kg weekly) of SC rozanolixizumab. The total weekly dose was similar in all treatment groups, ranging from 15 to 21 mg/kg.
Clinically relevant improvements (i.e., reaching >=50x10(9)/L) in platelet count and decreases in immunoglobin G (IgG) levels were observed across all dose groups, with higher response rate (55-67% in 1 x 15 mg/kg and 1 x 20 mg/kg dose groups vs 36-45% in 5 x 4 mg/kg, 3 x 7 mg/kg and 2 x 10 mg/kg dose groups) and shorter time to response achieved by the 1 x 15 mg/kg and 1 x 20 mg/kg rozanolixizumab dose groups.(i)
Results confirm that rozanolixizumab was well tolerated across all dose groups,(([i])) consistent with previous rozanolixizumab studies.([ii],[iii]) The most commonly reported adverse event was headache, with mild-to-moderate headaches seen at higher doses; other reported adverse events included diarrhea and vomiting. These events were usually of short duration and the majority of events resolved without treatment. No patient discontinued the study due to side effects.(i)
"ITP is a severe, often chronic disease that can have a significant, long-term impact on people's health and quality of life. Despite approved therapies, there is still an urgent need for new treatment options that are well tolerated and provide a sustained increase in platelet count," said Professor Tadeusz Robak, Professor of Hematology at the Medical University of Lodz, Poland. "These Phase II results for rozanolixizumab suggest the treatment could reduce IgG autoantibody levels and improve platelet count for people living with primary ITP."
Individuals living with ITP experience unpredictable and debilitating symptoms including spontaneous bruising, bleeding and fatigue that can greatly impact their activities of daily life.(([iv])) Additionally, the limited current treatment options for people with ITP can be time-consuming and invasive. There is a need to discover new solutions that have the potential to improve patients' health outcomes and quality of life. Rozanolixizumab is an advanced SC anti-neonatal Fc receptor (FcRn) therapy currently in clinical development and has the potential to provide a targeted, convenient option to optimize individualized patient care.
"Our research has enabled us to better understand rare, IgG autoantibody-mediated diseases such as ITP, including where gaps exist within the treatment paradigm and the overall patient experience," said Dr. Iris Loew-Friedrich, Chief Medical Officer, Executive Vice-President, UCB. "These results reaffirm our belief that targeting the neonatal Fc receptor pathway could have the potential to transform the treatment experience for people with ITP. We look forward to expanding this knowledge in Phase III trials in ITP and other patient populations."
About the rozanolixizumab clinical study(i)
TP0001 (NCT02718716) is a Phase II, multi-center, open-label, multiple-dose study of rozanolixizumab in patients with primary ITP. Sixty-six patients were assigned to one of five groups with different dosing regimens (5 x 4 mg/kg, 3 x 7 mg/kg, 2 x 10 mg/kg weekly, 1 x 15 mg/kg or 1 x 20 mg/kg), receiving rozanolixizumab by SC infusion (multiple doses were administered at weekly intervals). All patients were monitored for an 8-week observation period after completion of treatment. The primary objective of the study assessed safety and tolerability of rozanolixizumab administered by SC infusion, and the secondary objective considered the clinical efficacy (platelet count) and pharmacodynamic (total IgG) effects. The study was designed to explore a range of therapeutic doses in order to develop an appropriate dosing regimen for patients with ITP.
Rozanolixizumab was well tolerated across all dose groups (4-20 mg/kg) with mild-to-moderate headaches seen at higher doses; no patient discontinued the study due to side effects.
In the study, clinically relevant improvements in platelet count (to >=50x10(9)/L) were observed in patients with primary ITP receiving rozanolixizumab across all dose groups and decreases in serum IgG concentration were observed. By day 8, more patients receiving a single, higher-dose infusion achieved platelet counts of >=50x10(9)/L (58.3% and 54.5% in the 1 x 15 mg/kg and 1 x 20 mg/kg dose groups, respectively) compared with patients in the multiple-dose cohorts (7.1%, 14.3% and 27.3% in the 5 x 4 mg/kg, 3 x 7 mg/kg, and 2 x 10 mg/kg groups, respectively). A faster time to response was also observed in the 1 x 15 and 1 x 20 mg/kg dose groups (median 7 days and 5 days, respectively), compared with patients in the multiple-dose cohorts (14 days in both the 5 x 4 mg/kg and 3 x 7 mg/kg groups and 8 days in the 2 x 10 mg/kg group) following treatment.
About primary immune thrombocytopenia
Primary ITP is an acquired autoimmune disorder characterized, in most cases, by the presence of pathogenic IgG autoantibodies, with an estimated prevalence of approximately 10 people per 100,000 (USA)([v]). Pathogenic IgG autoantibodies target platelets and megakaryocytes (platelet precursors), leading to the removal and destruction of both circulating and newly formed platelets([vi],[vii],[viii]) ultimately resulting in a propensity for bleeding in patients with ITP. The standard of care for patients with newly diagnosed ITP consists of corticosteroids or intravenous immunoglobulin (IVIg).(([ix])) Patients intolerant to corticosteroids or with contraindications are treated with IVIg or anti-D (where appropriate), either alone or in combination. Subsequent treatments include immunosuppressive agents (e.g., azathioprine and mycophenolate mofetil), rituximab, TPO receptor agonists (e.g., eltrombopag and romiplostim) or splenectomy.(([x]))
Rozanolixizumab is a subcutaneously administered, humanized monoclonal antibody that specifically binds, with high affinity, to human FcRn. It has been designed to block the interaction of FcRn and IgG, inhibiting IgG recycling and inducing the removal of pathogenic IgG autoantibodies.([ii],[xi])
Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases, including ITP, myasthenia gravis (MG) and chronic inflammatory demyelinating polyneuropathy (CIDP), by driving removal of pathogenic IgG autoantibodies.
Rozanolixizumab, an investigational monoclonal antibody, was granted orphan drug designation for the treatment of ITP by the US Food and Drug Administration on 30 April 2018 and by the European Commission on 11 January 2019.([xii],[xiii]) The safety and efficacy of rozanolixizumab has not been established; it is not currently approved by any regulatory authority worldwide.
UCB, Brussels, Belgium (www.ucb.com [http://www.ucb.com/]) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With 7,500 people in approximately 40 countries, the company generated revenue of EUR4.6 billion in 2018. UCB is listed on Euronext Brussels . Follow us on Twitter: @UCB_news
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees.
Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. UCB is providing this information as of the date of this document and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.
There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.
Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.
[i] Robak, T., Kasmierczak, M., Jarque, I. et al. (2019). Rozanolixizumab, an anti-FcRn Antibody: Final results from a phase II, multiple-dose study in patients with primary immune thrombocytopenia. Blood. 134(1)
[ii] Kiessling, P., R. Lledo-Garcia, S. Watanabe et al. (2017) The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 9(414)
[iii] Bril, V., M. Benatar, M. Brock et al. (2019) Proof-of-Concept and Safety of the Anti-FcRn Antibody Rozanolixizumab in Patients with Moderate-to-Severe Generalized Myasthenia Gravis (GMG): A Phase 2a Study. Neurology(Abstracts: AAN 71th Annual Meeting, Philadelphia):pS43.001
[iv] Kohli, R. and S. Chaturvedi (2019) Epidemiology and Clinical Manifestations of Immune Thrombocytopenia. Hamostaseologie(EFirst)
[v] National Organization for Rare Disorders (NORD). Immune thrombocytopenia. Retrieved from: https://rarediseases.org/rare-diseases/immune-thrombocytopenia/ [https://rarediseases.org/rare-diseases/immune-thrombocytopenia/] Accessed December 2019
[vi] Cortelazzo, S., G. Finazzi, M. Buelli, A. Molteni, P. Viero, and T. Barbui (1991) High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood. 77(1):p31-3
[vii] Chang, M., P.A. Nakagawa, S.A. Williams et al. (2003) Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 102(3):p887-95
[viii] Chan, H., J.C. Moore, C.N. Finch, T.E. Warkentin, and J.G. Kelton (2003) The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 122(5):p818-24
[ix] Neunert, C., W. Lim, M. Crowther et al. (2011) The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 117(16):p4190-207
[x] Provan, D., R. Stasi, A.C. Newland et al. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 115(2):p168-86
[xi] Smith B, Kiessling A, Lledo-Garcia R, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs2018;10:1111-30
[xii] U.S. Food and Drug Administration (FDA). (2018). Orphan drug designations and approvals. Retrieved from: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=636618 [https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=636618] Accessed December 2019
[xiii] European Medicines Agency (EMA). (2019). Public summary of opinion on orphan designation. Retrieved from: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182131 [https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3182131] Accessed December 2019
CONTACT: Corporate Communications; Jim Baxter, Neurology Communications (Global), UCB T: +32-2-473-78-85-01, firstname.lastname@example.org / Laurent Schots, Media Relations, (Global) UCB, T: +32-2-559-92-64, email@example.com / Ally Funk, U.S. Communications, UCB, T: +1-770-970-8338, firstname.lastname@example.org / Investor Relations; Antje Witte, Investor Relations, UCB, T: +32-2-559-94-14, email@example.com / Isabelle Ghellynck, Investor Relations, UCB, T: +32-2-559-95-8, firstname.lastname@example.org
Web site: http://www.ucb.com/