Pharming Announces Positive Data from Phase II/III Leniolisib Trial Presented at Clinical Immunology Society 2022 Annual Meeting
PR95288
LEIDEN, Netherlands, April 2, 2022 /PRNewswire=KYODO JBN/ --
Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam:
PHARM/Nasdaq: PHAR) announces new data from the pivotal Phase II/III trial of
leniolisib for the treatment of activated phosphoinositide 3-kinase delta (PI3K
delta) syndrome (APDS), a primary immunodeficiency. Principal Investigator V.
Koneti Rao, M.D., a staff physician in the Primary Immune Deficiency Clinic at
the National Institutes of Health in Bethesda, Maryland, shared the findings in
a presentation at the Clinical Immunology Society (CIS) 2022 Annual Meeting (
https://cis.clinimmsoc.org/education/meetings/am22 ).
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As announced on February 2, 2022, the multinational, triple-blind,
placebo-controlled, randomized, Phase III portion of the clinical trial,
conducted by Novartis, met its co-primary endpoints, which evaluated reduction
in lymph node size and correction of immunodeficiency. The shrinking of
lymphadenopathy lesions and increased proportion of naive B cells are important
in this population, as they indicate a reduction in APDS disease markers.
Presented for the first time at CIS, the co-primary endpoints at day 85 after
baseline demonstrated:
-- In the index lymphadenopathy lesions, a statistically significant
adjusted mean change in the log10 transformed sum of product of
diameters (SPD) of -0.30 among patients who received leniolisib
compared with -0.06 among patients who received placebo (95% CI: -
0.37, -0.11; p=0.0012).
-- From a baseline level of <48%, an increase of 34.76% in the
proportion of naive B cells in patients who received leniolisib
versus a -5.37% decrease in patients who received placebo
(95% CI: 28.51, 51.75; p<0.0001).
The study drug was well-tolerated. There were no adverse events that led to
discontinuation of study treatment, there were no deaths, and the incidence of
serious adverse events (SAEs) was lower in the leniolisib group than in the
placebo group. None of the SAEs were suspected to be related to study treatment.
Charlotte Cunningham-Rundles, M.D., Ph.D., David S. Gottesman Professor of
Immunology at the Mount Sinai School of Medicine in New York, said:
"It is great news that leniolisib has achieved such positive results in this
Phase III study in APDS. It is extremely encouraging to see that this
medication is capable of targeting the cause of this difficult disease, both
improving care and reducing patients' symptoms. Progress toward a treatment
that is tailor-made for our patients with APDS is a milestone we have long
awaited."
Pharming plans to begin submitting global regulatory filings for leniolisib in
the second quarter of 2022 and, subject to approval, launching the treatment in
the U.S. in the first quarter of 2023 and starting a series of European
launches in the second half of 2023.
Anurag Relan, Chief Medical Officer of Pharming, commented:
"Pharming is delighted that leniolisib achieved significance in both co-primary
endpoints and was well tolerated in these APDS patients, as the product's
approval would address an unmet need for those with this rare disease, who
currently rely on supportive therapies such as antibiotics and immunoglobulin
replacement therapy. In addition to working closely with regulatory authorities
across the globe to make leniolisib available to immunologists, hematologists,
and their patients, we will continue to develop this treatment through our
open-label extension study and two additional studies that will enroll children
under the age of 12, as well as potentially extending the geographic reach of
the product."
About Activated Phosphoinositide 3-Kinase delta Syndrome (APDS)
APDS is a rare primary immunodeficiency that affects approximately one to two
people per million. Also known as PASLI, it 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.(1,2) 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.(1,3) APDS is characterized by severe,
recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and
enteropathy.(4,5) 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.(6) As APDS
is a progressive disease, this delay may lead to an accumulation of damage over
time, including permanent lung damage and lymphoma.(4-7) 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 with immunomodulating and potentially
anti-neoplastic activities. Leniolisib inhibits the production of
phosphatidylinositol-3-4-5-trisphosphate (PIP3). PIP3 serves as an important
cellular messenger specifically 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 delta and PI3K gamma are
expressed primarily in cells of hematopoietic origin. The central role of PI3K
delta 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 PI3K delta
is a valid and potentially effective therapeutic target for several immune
diseases.
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.
About Pharming Group N.V.
Pharming Group N.V. is a global, commercial stage biopharmaceutical company
developing innovative protein replacement therapies and precision medicines for
the treatment of rare diseases and unmet medical needs.
The flagship of our portfolio is our recombinant human C1 esterase inhibitor
(rhC1INH) franchise. C1INH is a naturally occurring protein that down regulates
the complement and contact cascades in order to control inflammation in
affected tissues.
Our lead product, RUCONEST(R), is the first and only plasma-free rhC1INH
protein replacement therapy. It is approved for the treatment of acute
hereditary angioedema (HAE) attacks. We are commercializing RUCONEST(R) in the
United States, the European Union and the United Kingdom through our own sales
and marketing organization, and the rest of the world through our distribution
network.
In addition, we are investigating the clinical efficacy of rhC1INH in the
treatment of further indications, including pre-eclampsia, acute kidney injury
and severe pneumonia as a result of COVID-19 infections.
We are also studying our oral precision medicine, leniolisib (a
phosphoinositide 3-kinase delta, or PI3K delta, inhibitor), for the treatment
of activated PI3K delta syndrome, or APDS. World-wide rights for leniolisib
were licensed from Novartis AG in 2019. Leniolisib met both of its primary end
points in a registration enabling Phase 2/3 study in the United States and
Europe. We are targeting global regulatory filings for leniolisib from Q2 2022
onwards.
Additionally, we entered into a strategic collaboration with Orchard
Therapeutics to research, develop, manufacture and commercialize OTL-105, a
newly disclosed investigational ex-vivo autologous hematopoietic stem cell
(HSC) gene therapy for the treatment of HAE.
Furthermore, we are leveraging our transgenic manufacturing technology to
develop next-generation protein replacement therapies, most notably for Pompe
disease, which is currently in preclinical development.
Forward-looking Statements
This press release contains forward-looking statements, including with respect
to timing and progress of Pharming's preclinical studies and clinical trials of
its product candidates, Pharming's clinical and commercial prospects,
Pharming's ability to overcome the challenges posed by the COVID-19 pandemic to
the conduct of its business, and Pharming's expectations regarding its
projected working capital requirements and cash resources. These 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 2020 Annual Report and
the Annual Report on Form 20-F for the year ended December 31, 2020 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. 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.
References:
1. Lucas CL, et al. Nat Immunol. 2014;15:88-97.
2. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
3. Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol.
2019;143(5):1676-1687.
4. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
5. Maccari ME, et al. Front Immunol. 2018;9:543.
6. Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21.
7. Condliffe AM, Chandra A. Front Immunol. 2018;9:338.
For further public information, contact:
Pharming Group, Leiden, The Netherlands
Sijmen de Vries, CEO: T: +31 71 524 7400
Susanne Embleton, Investor Relations Manager: T: +31 71 524 7400 E:
investor@pharming.com
FTI Consulting, London, UK
Victoria Foster Mitchell/Alex Shaw
T: +44 203 727 1000
FTI Consulting, USA
Jim Polson
T: +1 (312) 553-6730
LifeSpring Life Sciences Communication, Amsterdam, The Netherlands
Leon Melens
T: +31 6 53 81 64 27
E: pharming@lifespring.nl
US PR:
Emily VanLare
E: Emily.VanLare@precisionvh.com
T: +1 (203) 985 5596
EU PR:
Dan Caley
E: Dan.caley@aprilsix.com
T: +44 (0) 787 546 8942
SOURCE Pharming Group N.V.
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