dm+d

Unassigned

New Medicines

Pluvicto Metastatic, prostate-specific membrane antigen (PSMA) positive prostate cancer - third-line and beyond

Information

Pluvicto
Radiopharmaceutical precursor
Advanced Accelerator Applications (AAA)
Advanced Accelerator Applications (AAA)

Development and Regulatory status

Approved (Licensed)
Recommended for approval (Positive opinion)
Approved (Licensed)
Oct 22Recommended for EU approval by CHMP. The recommended indication is “Pluvicto in combination with androgen deprivation therapy (ADT) with or without androgen receptor (AR) pathway inhibition is indicated for the treatment of adult patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with AR pathway inhibition and taxane based chemotherapy.” Pluvicto will be available as a 1000MBq/ml solution for injection/infusion [20].
Sep 22Pluvicto NHS list price £20,000 per vial [19].
Aug 22The UK licensed indication for Pluvicto vials (containing 7,400 MBq in 7.5mL to 12.5mL) is treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes [18].
Aug 22Approved in UK [17].
Apr 22MHRA issues Early Access To Medicines Scheme (EAMS) status to to Advance Accelerator Applications for lutetium (177Lu) vipivotide tetraxetanin in the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes [16].
Mar 22FDA have approved lutetium Lu 177 vipivotide tetraxetan for use in adults with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer that has already metastasised to other body parts. The pts have already tried taxane based chemotherapy and androgen receptor pathway inhibition without success [15]
Mar 22Licensing decision due H1 22 and analysts predict that 177Lu-PSMA-617 has blockbuster potential with drug sales of up to $851 million anticipated by 2026 [14].
Nov 21Filed in EU via centralised procedure [13].
Sep 21US FDA has accepted and granted Priority Review to NDA for Lu-PSMA-617. With Priority Review, the Prescription Drug User Fee Act (PDUFA) date is anticipated in the first half of 2022. [12]
Sep 21Novartis is preparing for worldwide regulatory submissions which it expects to file by the end of 2021 [10].
Jun 21US FDA grant Breakthrough Therapy Designation for the treatment of metastatic castration-resistant prostate cancer (mCRPC) [8].
Mar 21The company announced plans to submit data from PIII VISION trial to regulatory authorities in the US and Europe.[6]
Dec 20Filings planned for 2021 [4].

Category

Theragnostic: 177LU-PSMA-617 is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irraditation of prostate cancer. Given every 6 weeks for 6 cycles.
Prostate-specific membrane antigen (PSMA) is a membrane-bound protein that is heavily expressed on PC cells. PSMA expression is nearly 100-fold higher in the prostate than in other tissues and is 10-fold higher in PC than in healthy prostate tissue. Its expression is further increased in higher-grade and metastatic cancers, and on development of castration resistance [1]. The age-standardised incidence of prostate cancer in England in 2016 was 173.7 per 100,000 [2].
Metastatic, prostate-specific membrane antigen (PSMA) positive prostate cancer - third-line and beyond
Intravenous infusion

Further information

Yes

Trial or other data

Sep 21Company announces positive health-related quality of life data from its PIII VISION RCT. It demonstrated delayed worsening of symptoms in pts taking Lu-PSMA-617 vs standard care alone. No new or unexpected safety concerns were found. [11]
Jun 21PIII VISION RCT (n=831) found radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival (median, 8.7 vs. 3.4 months; HR 0.40; 99.2% CI, 0.29 to 0.57; p<0.001) and overall survival (15.3 vs. 11.3 months; 0.62; 0.52 to 0.74; p<0.001) when added to standard care [9].
Jun 21177Lu-PSMA-617 improved OS in PIII VISION study, median 15.3 v 11.3 months, HR 0.62 [95% CI 0.52-0.74]; p<0.001 [7].
Mar 21Data from PIII VISION trial (n=831) show that 77Lu-PSMA-617 given 6 weekly for 6 cycles met primary endpoints and improved overall survival (OS) and radiographic progression-free survival (rPFS) vs. best standard of care in pts with PSMA-positive metastatic castration-resistant prostate cancer. Safety of the drug was consistent with previously reported data. Full data will be reported in due course. [6]
Sep 20PIII VISION study now due to complete collection of primary outcome data in Apr 21 [5].
Feb 20PIII VISION study is ongoing but no longer recruiting [3].
May 18PIII VISION study to compare overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/best standard of care versus patients treated with best supportive/best standard of care alone starts (NCT03511664). 750 adult men will be recruited in the US, Belgium, Canada, Denmark, France, Netherlands, Puerto Rico, Sweden and the UK. Collection of primary outcome data is due to complete Aug 20 [3].

Evidence based evaluations

PluvictoMetastatic, castration resistant prostate cancer (mCRPC) PSMA-positive - second-line (after ARDT and not exposed to a taxane-containing regimen)

Information

Pluvicto
Licence extension / variation
Advanced Accelerator Applications (AAA)
Advanced Accelerator Applications (AAA)

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Theragnostic: 177LU-PSMA-617 is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irraditation of prostate cancer. Given every 6 weeks for 6 cycles.
Prostate-specific membrane antigen (PSMA) is a membrane-bound protein that is heavily expressed on PC cells. PSMA expression is nearly 100-fold higher in the prostate than in other tissues and is 10-fold higher in PC than in healthy prostate tissue. Its expression is further increased in higher-grade and metastatic cancers, and on development of castration resistance [1]. In males in the UK, prostate cancer is the most common cancer, with around 52,300 new cases every year (2016-2018) [2].
Metastatic, castration resistant prostate cancer (mCRPC) PSMA-positive - second-line (after ARDT and not exposed to a taxane-containing regimen)
Intravenous infusion