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Thursday, December 15 2022 - 17:00
Pharming announces positive interim analysis data from open-label extension study of leniolisib in presentation at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition
LEIDEN, Netherlands, Dec. 15, 2022 /PRNewswire-AsiaNet/ --

V. Koneti Rao, MD, shared new evidence of long-term safety and hematologic 
response in patients who received leniolisib to treat APDS, a rare primary 

Interim analysis demonstrated leniolisib to be well tolerated and indicated the 
durability of the efficacy results seen in the Phase II/III randomized, 
controlled trial

Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam: PHARM) 
(Nasdaq: PHAR) announces data, including new evidence, from an interim analysis 
of its open-label extension study evaluating the investigational drug 
leniolisib, an oral, selective phosphoinositide 3-kinase delta (PI3K[Delta]) 
inhibitor, to treat adult and adolescent patients with activated 
phosphoinositide 3-kinase delta syndrome (APDS), a rare 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, U.S., shared the positive findings in an oral presentation 
at the 2022 Annual Meeting of the American Society of Hematology (ASH).

Dr. Virgil Dalm, Principal Investigator, Consultant Clinical Immunology, 
Erasmus MC, Rotterdam, the Netherlands, commented:

"I'm excited about Pharming's findings that further support leniolisib as a 
well-tolerated investigational treatment benefitting patients with APDS. The 
results demonstrate the long-term tolerability of leniolisib, with a median 
duration on study therapy of just over 2 years (102 weeks) and 5 subjects being 
treated for 5 years or more. Individuals with APDS frequently suffer from 
recurrent infections and lifelong Immunoglobulin Replacement Therapy (IRT) is 
required to reduce this burden. Notably, leniolisib treatment demonstrated a 
significant reduction in the annualized infection rate, while 37% of study 
patients on IRT were able to either reduce or altogether stop their IRT 
regimens. This is a remarkable outcome for any study of inborn errors of 
immunity and through the continued study of leniolisib, I look forward to 
contributing to the knowledge of an improved treatment option for individuals 
with APDS."

The ongoing extension study includes 37 patients with APDS aged 12 years or 
older who, at the time of data cutoff for the interim analysis, had received 70 
mg of the selective PI3K[Delta] inhibitor leniolisib twice a day for up to six 
years and three months, with a median duration on study therapy of 102 weeks. 
The study was primarily designed to assess the safety and tolerability of 
long-term leniolisib treatment in adolescent and adult patients with APDS who 
previously participated in a Phase II/III leniolisib study. The extension 
study's secondary endpoints are intended to evaluate the efficacy and 
pharmacokinetics of long-term leniolisib treatment in these patients.

The interim analysis found that leniolisib was well tolerated to this point in 
the study. It also indicated the durability of the efficacy results seen in the 
randomized, controlled trial, which showed significant improvement over placebo 
in the co-primary endpoints of reduction in lymph node size and increase in 
naive B cells. The interim results indicate a favorable long-term impact on the 
immune dysregulation and deficiency often seen in patients with APDS, with 
clinical manifestations including infections, lymphoproliferation, 
autoimmunity, enteropathy, bronchiectasis, increased risk of lymphoma, and 
early mortality.

The majority of adverse events (AEs) reported in the interim analysis were 
grades 1 and 2, and included upper respiratory tract infection, headache and 
pyrexia. Grade 1 AEs are the least severe and grade 5 the most severe. Overall, 
13.5% of AEs were study drug-related; these affected five patients and included 
weight gain, arthralgia, hyperglycemia, and decreased neutrophil count. Of all 
AEs assessed in the analysis, 16.2% were classified as serious, but none of 
these were identified as related to study treatment. There was one death among 
study participants which was identified as not related to study treatment.

Among study participants, some experienced reductions in APDS disease markers, 
with levels of response varying between individuals. Responses included:
- reduced lymphadenopathy, splenomegaly, and IgM levels;
- improved or resolved anemia, thrombocytopenia, and lymphopenia; and
- resolved neutropenia in all affected patients.

Importantly, 37% of participants who were on immunoglobulin replacement therapy 
(IRT) were able to reduce their IRT use while taking leniolisib. Six patients 
became IRT-independent, with four of those patients having been IRT-independent 
for 1 to 2.5 years at the data cutoff. As of the data cut-off for the interim 
analysis, among three patients who had a history of lymphoma prior to the 
trial, none had a recurrence or new lymphoma while participating in the study.

Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:

"Pharming is pleased to share positive interim findings on the long-term safety 
and efficacy of leniolisib. The results announced at the 2022 ASH Annual 
Meeting build on the Phase II/III study findings announced earlier this year 
and published in Blood[1] in November 2022, which highlighted leniolisib's 
potential to control the development of immune-related symptoms of APDS. We're 
proud to help fill an unmet need by developing what could become the first 
approved drug to target the cause of APDS."

The interim analysis findings are consistent with the data, first reported on 
February 2, 2022, for the Phase II/III clinical trial investigating leniolisib 
as a treatment for adult and adolescent patients with APDS. Compared with 
placebo, patients in the Phase II/III clinical trial achieved significant 
reductions in index lymph node size and increases in the percentage of naive B 
cells in peripheral blood.

Based on the results of Phase II/III clinical trial and the long-term, 
open-label extension data, the U.S. Food and Drug Administration (FDA) is 
conducting a priority review of Pharming's New Drug Application for leniolisib 
as a treatment for adolescents and adults with APDS and has an assigned 
Prescription Drug User Fee Act (PDUFA) goal date of March 29, 2023. In 
addition, Pharming's Marketing Authorisation Application (MAA) for leniolisib 
in the same patient population has been validated for evaluation under an 
accelerated assessment by the European Medicines Agency's (EMA) Committee for 
Medicinal Products for Human Use (CHMP). Marketing authorization for leniolisib 
in the European Union is anticipated in H1 2023.

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[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 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 

For more information, visit and find us on LinkedIn [ ].

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 
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"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.

Inside Information
This press release relates to the disclosure of information that qualifies, or 
may have qualified, as inside information within the meaning of Article 7(1) of 
the EU Market Abuse Regulation.

1.  Rao VK, et al. Blood. 2022.
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. 
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
T: +1 (908) 705 1696

Heather Robertson, Investor Relations & Corporate Communications Manager

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

Ethan Metelenis
T: +1 (917) 882 9038

Dan Caley
T: +44 (0) 787 546 8942

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Source: Pharming Group N.V.