On October 19, 2018 ArQule, Inc. (Nasdaq:ARQL) reported the presentation of preliminary clinical data on miransertib (ARQ 092) in three poster presentations at the American Society of Human Genetics (ASHG) 2018 Annual Meeting held from October 16 to 20, 2018 in San Diego (Press release, ArQule, OCT 19, 2018, View Source [SID1234529975]). The data presented relate to patients affected by either Proteus syndrome or PROS who have been receiving miransertib as part of a clinical trial or in a compassionate use setting.
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Two presentations feature data from two patients treated as part of ArQule’s named patient/compassionate use program. Presentation highlights include:
1.Personalized medicine in rare diseases and cancer: A case report of a lasting response in a young teenage patient with Proteus syndrome and secondary ovarian cancer
Treatment for the Proteus syndrome patient with concomitant relapsed ovarian cancer was administered at a dose level of 100mg and was well tolerated for over 19 months, resulting in a clinically significant/durable partial response of tumor and improvement of Proteus syndrome symptoms including improved mobility/bone changes
2.Severe PI3Kinase overgrowth syndrome treated with the AKT inhibitor miransertib
Treatment for the PROS patient was well tolerated for over 25 months resulting in clinical stabilization and radiological improvement of disease
"Our understanding of the potential for miransertib to target and treat these rare and devastating diseases that arise due to genetic alterations of the PI3K/AKT pathway has grown significantly since we partnered with The National Human Genome Research Institute in 2015 to conduct the first clinical trial in Proteus syndrome," said Brian Schwartz, M.D., Chief Medical Officer of ArQule. "The data we are presenting at ASH (Free ASH Whitepaper)G continues to highlight the promise of ArQule’s precision medicine approach for both rare diseases and oncology. We remain deeply committed to advancing miransertib for rare PI3K/AKT pathway overgrowth diseases as rapidly as possible, as there are currently no approved therapeutics for these patients."
A third presentation features data from patients treated as part of ArQule’s ongoing Phase 1/2, open label study of miransertib for the treatment of PROS. Study objectives include the evaluation of dosing schedule, safety, PK profile and preliminary efficacy of miransertib. Presentation highlights include:
3.An open-label, phase 1/2 study of miransertib (ARQ 092), an oral pan-AKT inhibitor, in patients (pts) with PIK3CA-related Overgrowth Spectrum (PROS): Preliminary results
Preliminary evidence of clinical efficacy was demonstrated by improvements in disease related symptoms and objective radiologic and photographic measures
Miransertib was well tolerated with a demonstrated manageable toxicity profile in patients as young as two years old
The recommended dose of miransertib, defined as 15 mg/m2 QD, with potential dose escalation to 25 mg/m2 QD, provided appropriate inhibition of the activated PIK3CA pathway for long-term use without inhibition of growth in normal healthy cells
Peter Lawrence, President and Chief Operating Officer of ArQule said: "This initial presentation of clinical data from our Phase 1/2 study in PROS lays the foundation for potentially expanding the miransertib rare disease program beyond Proteus syndrome, for which the drug already has received Rare Pediatric Disease and Fast Track Designation. We look forward to continuing our productive discussions with regulators to define a pivotal trial design and rapidly advance miransertib."
All posters presented by ArQule at the ASH (Free ASH Whitepaper)G 2018 Annual Meeting are available on the company’s website at View Source
About Miransertib
Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers; however, there are currently no approved inhibitors of AKT. AKT inhibitors, either as single agent or combination therapy, show significant promise in molecularly defined patient populations. Miransertib is currently in a Phase 1/2 company-sponsored study for PIK3CA-Related Overgrowth Spectrum (PROS), a Phase 1 study for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH/NHGRI), and a Phase 1b study in combination with the hormonal therapy, anastrozole, in patients with advanced endometrial cancer with AKT and PI3K mutations. Miransertib has been granted Rare Pediatric Disease Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA), as well as Orphan Designation by the FDA and European Medicines Agency in the rare overgrowth disease, Proteus syndrome.
About PROS
PROS is a term used to refer to a spectrum of rare diseases identified by somatic mutations in the PIK3CA gene, that result in excess growth in certain areas of the body. While the individual diseases that fall within the overgrowth spectrum have similar symptoms, each disease is defined by unique clinical characteristics. The implementation of genetic sequencing has led to the identification of the underlying genetic mutations that drive these overgrowth disorders, allowing for the development of medicines that target the specific causes of disease.
About Proteus Syndrome
Proteus syndrome is an ultra-rare condition characterized by the aberrant overgrowth of multiple tissues of the body. Patients with Proteus syndrome experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body. Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first 10 years of life. The worldwide incidence is believed to be approximately one in a million. There are currently no approved medicinal treatments for Proteus syndrome, leaving patients with minimal treatment options to manage the disease and a mortality of 25% by age 22.