Pharming Group announces start of Phase II clinical trial of leniolisib for primary immunodeficiencies (PIDs) with immune dysregulation
Pharming Group (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) has initiated a Phase II clinical trial to evaluate leniolisib in primary immunodeficiencies (PIDs) with immune dysregulation linked to altered PI3Kẟ signaling in lymphocytes. The trial will include patients with ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency, and PTEN deficiency, among others. These PIDs have a prevalence of approximately seven patients per million, compared to one to two per million for APDS.
The study, conducted at the National Institutes of Health (NIH), is a single arm, open-label, dose range-finding study with approximately 12 patients. It aims to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and explore clinical efficacy of leniolisib in the targeted PID population. This trial represents Pharming's second PID clinical program for leniolisib, expanding beyond its current approved use for APDS in adults and pediatric patients 12 years and older.
Pharming Group (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) ha avviato uno studio clinico di Fase II per valutare leniolisib nelle immunodeficienze primarie (PID) con disregolazione immunitaria legata alla segnalazione alterata di PI3Kẟ nei linfociti. Lo studio includerà pazienti con ALPS-FAS, insufficienza di CTLA4, insufficienza di NFKB1 e carenza di PTEN, tra gli altri. Queste PID hanno una prevalenza di circa sette pazienti ogni milione, rispetto a uno o due per milione per APDS.
Lo studio, condotto presso i National Institutes of Health (NIH), è uno studio a braccio singolo, a etichetta aperta e di ricerca della gamma di dosaggio che coinvolge circa 12 pazienti. Si propone di valutare sicurezza, tollerabilità, farmacocinetica, farmacodinamica ed esplorare l’efficacia clinica di leniolisib nella popolazione PID mirata. Questo studio rappresenta il secondo programma clinico PID per leniolisib di Pharming, ampliando l’uso oltre l’attuale approvazione per APDS in pazienti adulti e pediatrici di età pari o superiore a 12 anni.
Pharming Group (EURONEXT Ámsterdam: PHARM/Nasdaq: PHAR) ha iniciado un ensayo clínico de Fase II para evaluar leniolisib en inmunodeficiencias primarias (PID) con disfunción inmunitaria relacionada con la señalización alterada de PI3Kẟ en linfocitos. El ensayo incluirá pacientes con ALPS-FAS, insuficiencia de CTLA4, insuficiencia de NFKB1 y deficiencia de PTEN, entre otros. Estas PID tienen una prevalencia de aproximadamente siete pacientes por millón, en comparación con uno a dos por millón para APDS.
El estudio, realizado en los Institutos Nacionales de Salud (NIH), es un estudio de brazo único, abierto y de búsqueda de rango de dosis con aproximadamente 12 pacientes. Su objetivo es evaluar la seguridad, tolerabilidad, farmacocinética, farmacodinámica y explorar la eficacia clínica de leniolisib en la población PID objetivo. Este ensayo representa el segundo programa clínico PID para leniolisib de Pharming, ampliando su uso más allá de la aprobación actual para APDS en adultos y pacientes pediátricos de 12 años o más.
파밍 그룹(EURONEXT 암스테르담: PHARM/Nasdaq: PHAR)은 2상 임상 시험을 시작했습니다 조절된 PI3Kẟ 신호와 림프구의 면역적 부조화와 관련된 주요 면역 결핍증(PID)에서 leniolisib을 평가하기 위해. 이 시험에는 ALPS-FAS, CTLA4 반감소증, NFKB1 반감소증 및 PTEN 결핍증을 포함한 환자들이 포함됩니다. 이러한 PID의 유병률은 약 백만 명당 7명입니다. APDS의 경우는 백만 명당 1~2명입니다.
국립 보건원(NIH)에서 수행되는 이 연구는 싱글 암, 오픈 라벨, 용량 범위 탐색 연구입니다 약 12명의 환자를 목표로 하고 있습니다. 그 목적은 안전성, 내약성, 약동학, 약리학적 작용을 평가하고 목표 PID 집단에서 leniolisib의 임상 효능을 탐색하는 것입니다. 이 시험은 Pharming의 lenilisib을 위한 두 번째 PID 임상 프로그램으로, 12세 이상의 성인 및 소아 환자에 대한 APDS의 현재 승인된 사용을 넘어 확장됩니다.
Pharming Group (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) a initié un essai clinique de Phase II pour évaluer le leniolisib dans les immunodéficiences primaires (PID) avec une dérégulation immunitaire liée à une signalisation PI3Kẟ altérée dans les lymphocytes. L'essai inclura des patients atteints de ALPS-FAS, d'insuffisance en CTLA4, d'insuffisance en NFKB1 et de déficience en PTEN, entre autres. Ces PID ont une prévalence d'environ sept patients par million, contre un à deux par million pour l'APDS.
L'étude, réalisée aux National Institutes of Health (NIH), est une étude à bras unique, ouverte et de recherche de dose impliquant environ 12 patients. Elle vise à évaluer la sécurité, la tolérance, la pharmacocinétique, la pharmacodynamique et à explorer l'efficacité clinique du leniolisib dans la population PID ciblée. Cet essai représente le deuxième programme clinique PID pour le leniolisib de Pharming, se développant au-delà de son utilisation approuvée actuelle pour l'APDS chez les adultes et les patients pédiatriques de 12 ans et plus.
Die Pharming Group (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) hat eine Phase-II-Studie begonnen, um Leniolisib bei primären Immundefizienzen (PID) mit immunregulatorischen Störungen zu bewerten, die mit einer veränderten PI3Kẟ-Signalübertragung in Lymphozyten verbunden sind. Die Studie wird Patienten mit ALPS-FAS, CTLA4-Haploinsuffizienz, NFKB1-Haploinsuffizienz und PTEN-Mangel umfassen, unter anderem. Diese PID haben eine Prävalenz von etwa sieben Patienten pro Million, im Vergleich zu ein bis zwei pro Million für APDS.
Die Studie, die an den National Institutes of Health (NIH) durchgeführt wird, ist eine einarmige, offene Dosisfindungsstudie mit etwa 12 Patienten. Ziel ist es, Sicherheit, Verträglichkeit, Pharmakokinetik, Pharmakodynamik zu bewerten und die klinische Wirksamkeit von Leniolisib in der Ziel-PID-Population zu erkunden. Diese Studie stellt Pharmings zweites klinisches Programm für PID mit Leniolisib dar, das über die derzeit genehmigte Anwendung bei APDS bei Erwachsenen und pädiatrischen Patienten ab 12 Jahren hinausgeht.
- Initiation of Phase II clinical trial for leniolisib in new PIDs
- Potential to address unmet medical needs in rare PID disorders
- Expanded market opportunity with higher prevalence (7 per million) compared to APDS (1-2 per million)
- Collaboration with National Institutes of Health (NIH) for the clinical trial
- Early-stage clinical trial with uncertain outcomes
- Small patient population in the study (approximately 12 patients)
Insights
This Phase II clinical trial for leniolisib represents a significant expansion of Pharming's research into primary immunodeficiencies (PIDs) beyond APDS. The study targets PIDs with immune dysregulation linked to altered PI3Kẟ signaling, including ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency.
Key points:
- The targeted PID population has a prevalence of
~700% compared to APDS, potentially expanding leniolisib's market. - The trial aims to assess safety, tolerability, pharmacokinetics, pharmacodynamics and explore clinical efficacy in approximately 12 patients.
- Conducted at the NIH, the study benefits from expertise of senior research physicians in the field.
- Results will inform a potential Phase III program, suggesting a strategic long-term plan for leniolisib's development.
This move could significantly broaden leniolisib's application in rare PIDs, potentially addressing unmet medical needs in a larger patient population. The involvement of the NIH adds credibility and might accelerate the research process.
Pharming's expansion of leniolisib into new PIDs represents a strategic move to leverage its existing asset and potentially increase its market reach. Key financial implications include:
- Market Expansion: The targeted PID population is approximately 5 times larger than APDS, potentially increasing leniolisib's addressable market significantly.
- R&D Investment: While specific costs aren't mentioned, this Phase II trial likely represents a substantial R&D investment for Pharming.
- Risk Mitigation: By diversifying leniolisib's applications, Pharming reduces reliance on a single indication, potentially de-risking its portfolio.
- Future Revenue Potential: If successful, this could lead to additional revenue streams, though commercialization is likely years away.
Investors should monitor trial progress and any interim results, as positive outcomes could significantly impact Pharming's long-term value proposition. However, as with any clinical trial, there are inherent risks of failure that could impact the company's resources and stock performance.
Proof of concept clinical trial will evaluate leniolisib in PIDs with immune dysregulation linked to altered PI3Kẟ signaling in lymphocytes
PIDs to include ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency, with prevalence approximately five times that of APDS
Clinical trial being conducted at the National Institutes of Health (NIH)
Leiden, the Netherlands, October 10, 2024: Pharming Group N.V. (“Pharming” or “the Company”) (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) announces the start of a Phase II, proof of concept, clinical trial evaluating leniolisib in primary immunodeficiencies (PIDs) with immune dysregulation linked to altered PI3Kẟ signaling in lymphocytes.
The clinical trial is open for enrollment and will include PID patients with ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency, among others. These PID patients exhibit altered PI3Kẟ signaling in lymphocytes and likewise display similar clinical phenotypes to activated phosphoinositide 3-kinase delta syndrome (APDS) patients. Epidemiology suggests a prevalence of approximately seven patients per million in this targeted PID population, compared to one to two patients per million for APDS.
The Phase II clinical trial is a single arm, open-label, dose range-finding study to be conducted in approximately 12 patients. The objectives for the trial will be to assess safety and tolerability, pharmacokinetics, pharmacodynamics, and explore clinical efficacy of leniolisib in the targeted PID population. The trial has been designed to inform a subsequent Phase III program. The Phase II clinical trial is being conducted at the National Institute of Allergy and Infectious Diseases (NIAID) – part of the National Institutes of Health (NIH) – with lead investigator Gulbu Uzel, M.D., Senior Research Physician, and co-investigator V. Koneti Rao, M.D., FRCPA, Senior Research Physician, Primary Immune Deficiency Clinic (ALPS Clinic).
Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:
“The initiation of this study is an important milestone for Pharming as it represents the second primary immunodeficiency (PID) clinical program for leniolisib. Based on our experience in APDS, and the significant role of PI3Kd in regulating lymphocytes, leniolisib has the potential to address the underlying immune dysregulation and deficiency in a number of rare PID disorders with significant unmet medical needs, including ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency. We are excited to be leading this important scientific effort and to sharing the results of the study with the medical community.”
The first patient is expected to be enrolled in the study in the coming weeks.
This is the first clinical trial initiated by Pharming to study leniolisib in PIDs with immune dysregulation beyond APDS. The unique genetic drivers in ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN patients lead to enhanced PI3Kd signaling and clinical phenotypes of immune dysregulation shared with APDS. Specifically, PTEN patients with immunodeficiency are frequently described as ‘APDS-like’1, patients with ALPS-FAS display predominantly lymphoproliferative clinical manifestations with frequent cytopenic episodes2, and CTLA4 haploinsufficiency3 as well as NFKB1 haploinsufficiency4 patients demonstrate lymphoproliferative, cytopenic, and/or organ-specific autoimmune/inflammatory complications of immune dysregulation.
Leniolisib is marketed in the U.S. and approved in several other countries, for the treatment of APDS in adult and pediatric patients 12 years of age and older.
About leniolisib
Leniolisib is an oral small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor approved in the U.S. and several other countries as the first and only targeted treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, which serves as an important cellular messenger and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase III clinical trial demonstrated statistically significant improvement in the coprimary endpoints, reflecting a favorable impact on the immune dysregulation and deficiency seen in these patients, and interim open label extension data has supported the safety and tolerability of long-term leniolisib administration.5,6 Leniolisib is currently under regulatory review in the European Economic Area, Canada and Australia for APDS, with plans to pursue further regulatory approvals in Japan and South Korea. Leniolisib is also being evaluated in two Phase III clinical trials in children with APDS and in a Phase II clinical trial in primary immunodeficiencies (PIDs) with immune dysregulation linked to altered PI3Kẟ signaling in lymphocytes. The safety and efficacy of leniolisib has not been established for PIDs with immune dysregulation beyond 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 and biologics. Pharming is headquartered in Leiden, the 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.
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, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2023 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2023, 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 forward-looking statement as a result of new information, future events or other information.
References
- Tsujita Y, et al. J Allergy Clin Immunol 2016;138:1672-80.
- Bride K & Teachey D. F1000Res. 2017;6:1928.
- Kuehn HS, et al. Science 2014;345:1623-27.
- Lorenzini T, et al. J Allergy Clin Immunol 2020;146:901-11.
- Rao VK, et al Blood. 2023 Mar 2;141(9):971-983.
- Rao VK, et al. J Allergy Clin Immunol 2024;153:265-74.
For further public information, contact:
Pharming Group, Leiden, the Netherlands
Michael Levitan, VP Investor Relations & Corporate Communications
T: +1 (908) 705 1696
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
Christina Renfroe
T: +1 (636) 352-7883
E: Christina.Renfroe@precisionaq.com
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