Signifor (pasireotide)

The multifaceted actions and effects of somatostatin make it useful as a potential therapeutical means in various pathologies; however, in clinical practice, somatostatin analogues, namely octreotide, lanreotide and pasireotide, are commonly used instead, due to their increased half-life and increased receptor selectivity, with pasireotide showing a more extensive receptor binding profile and high affinity for somatotastin receptor (SSTR) 5, which may prove effective in cases of resistance to first-generation analogues...They have also been used in some cases, with varying degrees of success, in patients with post-surgical gastrointestinal and lymphatic fistulas, refractory chronic diarrhoea and polycystic kidney disease; many applications in paediatric patients have also been documented. The aim of this review is to present the applications of somatostatin and its analogues as alternative or second-line therapies, along with insights into their effectiveness and future potential.

P3, N=240, Recruiting, Novartis Pharmaceuticals | N=100 --> 240

P3, N=240, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2030 --> Dec 2028

Treatment with somatostatin, cortistatin, octreotide or pasireotide did not exert clear antitumoral effects on model cell lines...Molecular analysis revealed a generalized dephosphorylation affecting key proliferation, growth and cell survival pathways in response to BIM-23120 (unlike when treating with octreotide). Altogether, our results provide novel information on the status of the somatostatin system in PPGL and identify new potential therapeutic tools selectively targeting somatostatin receptors on this refractory tumor.

Clinical management often requires a multimodal approach including titration of DA to higher than usual doses, surgical resection or debulking, and targeted radiotherapy. Robust evidence is lacking for non-approved adjunct therapies, such as aromatase inhibitors and estrogen receptor modulators, although the somatostatin receptor ligand pasireotide may have potential in select patients.

The human insulinoma-derived NT-3 cell line and the murine AtT-20 corticotroph cell line, both expressing SSTR2 and SSTR5, were treated with 1-50 nM of the novel SRLs or reference agents (octreotide, pasireotide)...Dual SSTR2/SSTR5 agonists exhibit antisecretory and antiproliferative activity in NET models that was similar or even superior to reference SRLs. These findings support their further development as next-generation SRLs for SSTR2/5-expressing tumors.

P1, N=40, Not yet recruiting, Recordati AG

P1, N=40, Completed, RECORDATI GROUP | Recruiting --> Completed

Despite multimodal therapy (lanreotide, cabergoline, two debulking surgeries), disease control was achieved only after pasireotide and adjuvant proton therapy. The same variant was found in her father, who had a smaller intrasellar macroadenoma causing acromegaly. This familial observation provides the functional evidence that MAX is a driver in GH-PitNET and a candidate gene for PitNET predisposition.

P1, N=40, Recruiting, RECORDATI GROUP

Patient 2, 48-year-old male with a significant macroadenoma and prior cabergoline treatment, achieved partial biochemical control. Four out of these five patients showed reduction in tumour size. This case series corroborates the findings from previous studies, adding insight into treatment challenges and benefits experienced by this heterogeneous group of patients on pasireotide.

In conclusion, our results suggest that FLNA may be associated with tumor invasiveness in GH-secreting pituitary tumors. While data on Pasireotide-treated patients are exploratory, further studies are needed to assess FLNA's potential as a treatment response marker in acromegaly.