Pharming announces publication of data from Phase 3 Study of leniolisib in patients with APDS in ASH's Blood
PR99112
LEIDEN, Netherlands, Dec. 7, 2022 /PRNewswire=KYODO JBN/--
Leniolisib was well tolerated and significant improvement over placebo was
notable in the co-primary endpoints, reflecting a favorable impact on patients'
immune dysregulation and deficiency
The peer-reviewed publication heightens international understanding of APDS, a
rare and recently characterized immunodeficiency
Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam: PHARM)
(Nasdaq: PHAR) announces today that the positive results of a Phase 3 clinical
trial of the investigational drug leniolisib, an oral, selective
phosphoinositide 3-kinase delta (PI3K[delta]) inhibitor, in adult and
adolescent patients with activated phosphoinositide 3-kinase delta syndrome
(APDS), a rare primary immunodeficiency, have been published in Blood,1 the
peer-reviewed international medical journal of the American Society of
Hematology (
). Data from this study was previously announced on February 2, 2022.
The paper, entitled 'Randomized, Placebo-Controlled, Phase 3 Trial of
PI3K[delta] Inhibitor Leniolisib for Activated PI3K[delta] Syndrome', outlined
results from the multinational, triple-blind, placebo-controlled, randomized
clinical trial, which enrolled 31 patients with APDS aged 12 years or older.
Patients were randomly assigned in a 2:1 ratio to receive 70 mg leniolisib or
placebo twice daily for 12 weeks. Improvement over placebo was significant in
the co-primary endpoints which evaluated reduction in lymph node size and
increase in naive B cells, reflecting the impact on immune dysregulation and
correction of immunodeficiency in these patients, respectively. The adjusted
mean change (95% CI) between leniolisib and placebo for lymph node size was
-0.25 (-0.38, -0.12; P=0.0006; N=26) and for percentage of naive B cells was
37.30 (24.06, 50.54; P=0.0002; N=13). Leniolisib was well tolerated, and fewer
patients receiving leniolisib reported study treatment-related adverse events
(mostly grades 1-2) compared to those receiving placebo (23.8% vs 30.0%).
Vicki Modell, co-founder of the Jeffrey Modell Foundation, an international,
non-profit, organization dedicated to helping individuals and family members
affected by primary immunodeficiency disorders, commented:
"Pharming continues to provide significant support for the immunodeficiency
community. The Jeffrey Modell Foundation is dedicated to early diagnosis and
finding meaningful treatments for primary immunodeficiency, and we are acutely
aware of the challenges faced by people with APDS. The publication of study
results in this patient population in such a distinguished and widely read
journal advances these goals."
Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:
"As we continue to seek a better understanding of APDS as a recently
characterized rare disease, we remain committed to sharing our findings with
researchers and doctors around the world. With this commitment in mind, we are
pleased the results of this Phase III clinical trial in leniolisib have been
published in the flagship journal of the American Society of Hematology.
The APDS patient population, and their families, have lived with unmet needs
and without targeted therapies, and the publishing of this study is an integral
step in improving the patient journey for this community. We are proud to share
these results which demonstrated leniolisib to be a well-tolerated, targeted
therapy for APDS. We thank all of our study participants and investigators for
their efforts and the essential role they played in the development of
leniolisib."
About Activated Phosphoinositide 3-Kinase [delta] Syndrome (APDS)
APDS is a rare primary immunodeficiency that affects approximately 1 to 2
people per million. APDS is caused by variants in either of two genes, PIK3CD
or PIK3R1, that regulate maturation of white blood cells. Variants of these
genes lead to hyperactivity of the PI3K[delta] (phosphoinositide 3-kinase
delta) pathway.2,3 Balanced signaling in the PI3K[delta] pathway is essential
for physiological immune function. When this pathway is hyperactive, immune
cells fail to mature and function properly, leading to immunodeficiency and
dysregulation.2,4 APDS is characterized by severe, recurrent sinopulmonary
infections, lymphoproliferation, autoimmunity, and enteropathy.5,6 Because
these symptoms can be associated with a variety of conditions, including other
primary immunodeficiencies, people with APDS are frequently misdiagnosed and
suffer a median 7-year diagnostic delay.7 As APDS is a progressive disease,
this delay may lead to an accumulation of damage over time, including permanent
lung damage and lymphoma.5-8 The only way to definitively diagnose this
condition is through genetic testing.
About Leniolisib
Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa
catalytic subunit of class IA PI3K. PI3K[delta] is expressed predominately in
hematopoietic cells and is essential to normal immune system function through
conversion of phosphatidylinositol-4-5-trisphosphate (PIP2) to
phosphatidylinositol-3-4-5-trisphosphate (PIP3). Leniolisib inhibits the
production of PIP3 and PIP3 serves as an important cellular messenger
activating AKT (via PDK1) and regulates a multitude of cell functions such as
proliferation, differentiation, cytokine production, cell survival,
angiogenesis, and metabolism. Unlike PI3K[alpha] and PI3K[beta], which are
ubiquitously expressed, PI3K[Gamma] and PI3K[delta] are expressed primarily in
cells of hematopoietic origin. The central role of PI3K[alpha] in regulating
numerous cellular functions of the adaptive immune system (B-cells and, to a
lesser extent, T cells) as well as the innate immune system (neutrophils, mast
cells, and macrophages) strongly indicates that PI3[delta] is a valid and
potentially effective therapeutic target for immune diseases such as APDS. To
date, leniolisib has been well tolerated during both the Phase 1 first-in-human
trial in healthy subjects and the Phase II/III registration-enabling study in
patients with APDS.
About Pharming Group N.V.
Pharming Group N.V. (EURONEXT Amsterdam: PHARM) (Nasdaq: PHAR) is a global
biopharmaceutical company dedicated to transforming the lives of patients with
rare, debilitating, and life-threatening diseases. Pharming is commercializing
and developing an innovative portfolio of protein replacement therapies and
precision medicines, including small molecules, biologics, and gene therapies
that are in early to late-stage development. Pharming is headquartered in
Leiden, Netherlands, and has employees around the globe who serve patients in
over 30 markets in North America, Europe, the Middle East, Africa, and
Asia-Pacific.
For more information, visit www.pharming.com and find us on LinkedIn
(https://www.linkedin.com/company/pharming/).
Forward-Looking Statements
This press release may contain forward-looking statements. Forward-looking
statements are statements of future expectations that are based on management's
current expectations and assumptions and involve known and unknown risks and
uncertainties that could cause actual results, performance, or events to differ
materially from those expressed or implied in these statements. These
forward-looking statements are identified by their use of terms and phrases
such as "aim", "ambition", "anticipate", "believe", "could", "estimate",
"expect", "goals", "intend", "may", "milestones", "objectives", "outlook",
"plan", "probably", "project", "risks", "schedule", "seek", "should", "target",
"will" and similar terms and phrases. Examples of forward-looking statements
may include statements with respect to timing and progress of Pharming's
preclinical studies and clinical trials of its product candidates, Pharming's
clinical and commercial prospects, and Pharming's expectations regarding its
projected working capital requirements and cash resources, which statements are
subject to a number of risks, uncertainties and assumptions, including, but not
limited to the scope, progress and expansion of Pharming's clinical trials and
ramifications for the cost thereof; and clinical, scientific, regulatory and
technical developments. In light of these risks and uncertainties, and other
risks and uncertainties that are described in Pharming's 2021 Annual Report and
the Annual Report on Form 20-F for the year ended December 31, 2021, filed with
the U.S. Securities and Exchange Commission, the events and circumstances
discussed in such forward-looking statements may not occur, and Pharming's
actual results could differ materially and adversely from those anticipated or
implied thereby. All forward-looking statements contained in this press release
are expressly qualified in their entirety by the cautionary statements
contained or referred to in this section. Readers should not place undue
reliance on forward-looking statements. Any forward-looking statements speak
only as of the date of this press release and are based on information
available to Pharming as of the date of this release. Pharming does not
undertake any obligation to publicly update or revise any.
References
[1] Rao VK, et al. Blood. 2022. https://doi.org/10.1182/blood.2022018546.
[2] Lucas CL, et al. Nat Immunol. 2014;15:88-97.
[3] Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
[4] Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol.
2019;143(5):1676-1687.
[5] Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
[6] Maccari ME, et al. Front Immunol. 2018;9:543.
[7] Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21.
[8] Condliffe AM, Chandra A. Front Immunol. 2018;9:338.
For further public information, contact:
Pharming Group, Leiden, The Netherlands
Michael Levitan, VP Investor Relations & Corporate Communications
Heather Robertson, Investor Relations & Corporate Communications Manager
E: investor@pharming.com
FTI Consulting, London, UK
Victoria Foster Mitchell/Alex Shaw/Amy Byrne
T: +44 203 727 1000
LifeSpring Life Sciences Communication, Amsterdam, The Netherlands
Leon Melens
T: +31 6 53 81 64 27
E: pharming@lifespring.nl
US PR
Ethan Metelenis
E: Ethan.Metelenis@precisionvh.com
T: +1 (917) 882 9038
EU PR
Dan Caley
E: Dan.caley@aprilsix.com
T: +44 (0) 787 546 8942
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Source: Pharming Group NV
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