Evidence Grade B — Strong clinical evidence. 178 published studies, 124 human. 67 registered clinical trials.
Medically reviewed by a licensed medical professional
This entry covers the investigational use of Pluvicto (lutetium-177 vipivotide tetraxetan) in earlier stages of prostate cancer than its current approval. Pluvicto is already approved for late-stage prostate cancer (see the separate Pluvicto entry); trials are now investigating whether using it earlier in the disease course — when tumours may be more responsive — produces better outcomes.
177Lu-PSMA-617 (Extended Indications) is also known by these brand and alternate names:
178 published studies: 124 human, 0 animal, 5 in-vitro, 26 reviews
Pluvicto is approved for late-stage prostate cancer (see compound #66). Extended-indication trials are investigating use in earlier disease stages. The PSMAfore trial (468 patients) showed significantly improved progression-free survival in pre-taxane patients. The PSMAddition trial is investigating combination with standard hormonal therapy in metastatic hormone-sensitive prostate cancer.
The strategic question is whether moving radioligand therapy earlier in the treatment sequence — when patients have less advanced disease and potentially more PSMA-expressing tumour cells — produces better outcomes. This is not a peptide.
The PSMA-617 ligand binds to prostate-specific membrane antigen (PSMA) on cancer cells. Upon binding, the construct is internalised into the cell, delivering targeted radiation that destroys the cancer cell while minimising damage to surrounding tissue. The investigation of earlier treatment lines aims to determine whether this targeted radiation approach is more effective when used before extensive prior therapy.
The PSMAfore trial (468 patients) showed significantly improved progression-free survival in patients who had not yet received chemotherapy, leading to an expanded FDA approval in March 2025. The larger PSMAddition trial is testing Pluvicto in combination with standard hormone therapy in newly diagnosed metastatic prostate cancer — a setting that could potentially double the eligible patient population. Key safety considerations include dry mouth (38-61%), bone marrow suppression, and the requirement for PSMA-PET imaging to confirm eligible patients. Manufacturing and supply chain constraints for the radioactive component (lutetium-177) remain a practical limitation. The strategic question is whether radioligand therapy earlier in the treatment sequence produces meaningfully different outcomes than its current late-stage use.
PeptideTrace tracks 67 registered clinical trials for 177Lu-PSMA-617 (Extended Indications) sourced from ClinicalTrials.gov.
177Lu-PSMA-617 Managed Access Program for mCRPC Patients
Impact of Body Composition on Dosimetry of 177Lu-PSMA Radioligand Therapy
68Ga-PSMA-11 PET-directed Radioligand Therapy in Metastatic Hepatocellular Carcinoma (HCC)
Lu-177 PSMA Treatment in Cell Renal Carcinoma
PSMA-High: EBRT/ PSMA617/ ADT vs. EBRT/ ADT
FDA ORIG 1
EMA Marketing Authorisation
FDA SUPPL 24
FDA SUPPL 21
Lutetium-177 vipivotide tetraxetan (brand name Pluvicto) is a radiolabeled PSMA-targeting small molecule ligand conjugated to the beta-emitting radioisotope Lutetium-177. NOTE: This is NOT a peptide. Developed by Novartis, acquired through Endocyte. Lutetium-177 has a half-life of approximately 6.7 days, delivering targeted beta radiation to PSMA-expressing prostate cancer cells. Administered as intravenous infusion at 7.4 GBq every 6 weeks for up to 6 cycles. Initial FDA approval March 23, 2022 for post-ARPI post-taxane mCRPC. This entry covers the extended indications program.
The PSMA-617 ligand binds with high affinity to prostate-specific membrane antigen expressed on prostate cancer cells. Upon binding, the construct is internalized, delivering Lutetium-177 beta radiation directly to tumor cells (maximum energy 0.497 MeV, tissue penetration approximately 2 mm). This produces DNA double-strand breaks and cell death in both directly targeted cells and nearby PSMA-negative tumor cells through crossfire radiation. The short tissue penetration limits damage to surrounding normal tissue.
The VISION pivotal trial (NCT03511664; N=831) demonstrated overall survival of 15.3 versus 11.3 months (HR 0.62; P<0.001) and radiographic PFS of 8.7 versus 3.4 months (HR 0.40; P<0.001). PSMAfore (NCT04689828; N=468; pre-taxane mCRPC): rPFS 11.6 versus 5.6 months (HR 0.41; P<0.0001); OS HR 0.91 (P=0.20, not significant, confounded by 60.3% crossover rate). PSMAddition (NCT04720157; metastatic hormone-sensitive prostate cancer): interim analysis met the primary rPFS endpoint (June 2025) with a positive overall survival trend. Expanded FDA approval was granted March 28, 2025 for post-ARPI pre-taxane mCRPC based on PSMAfore data.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
