PR99214

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=KYODO JBN/ --

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

immunodeficiency

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

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.

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.

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

T: +1 (908) 705 1696

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 N.V.