Based on findings from the VISION trial [1], the FDA approved 177Lu-PSMA-617 in March 2022 for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy [2]. Prostate cancer is the most common cancer in American men. While most men do not die from prostate cancer, around 34,000 are expected to die from it during 2023. It is the second leading cause of cancer death for American men, behind only lung cancer [3]. The problem that exists in the US with 177Lu-PSMA-617 (PLUVICTO®) is that the drug is in such short supply [4] that its maker, Advanced Accelerator Applications USA, Inc., owned by Novartis Pharmaceutical Co., stated on a CNN health program, that the company will be unable to supply it to new patients until it can produce greater quantities of the drug [5]. On April 21, 2023, Novartis released an update saying that “the FDA today approved our application to supply commercial doses of Pluvicto® from our Radioligand Therapy (RLT) manufacturing facility in Millburn, New Jersey, for distribution in the US” [6]. Nevertheless, a supply shortage is expected until Q3 of 2023 [7]. What are the options for American patients who are in urgent need of 177-Lu-PSMA radioligand treatment? Apart from 177Lu-PSMA-617 (PLUVICTO®) which, as stated, is FDA approved in the US, other non-FDA approved PSMA radioligands exist outside the US for the treatment of prostate cancer. These agents include PSMA-617, PSMA-I&T and monoclonal antibodies such as J591 linked to beta-emitters such as Lutetium-177 and Terbium-161, and alpha-emitters such as Actinium-225. Among those labeled with beta emitting isotopes, 177-Lu-PSMA-I&T has been the most predominantly studied. In a research paper published in the European Journal of Nuclear Medicine and Molecular Imaging in February 2022 by Philipp E. Hartrampf et al., titled “Matched‑pair analysis of [177Lu] Lu‑PSMA I&T and [177Lu] Lu-PSMA-617 in patients with metastatic castration‑resistant prostate cancer” performed on a cohort of 110 mCRPC patients, it was proven that “no relevant differences for overall survival (OS) were observed” [8]. In layman's words this means that both agents are achieving the same results with respect to life prolongation with no noticeable difference. Outside the US there are numerous centers offering radioligand therapy (RLT) with PSMA I&T, [9, 10, 11, 12]; these centers can be found in the EU, Turkey, South Africa, South America, Australia, New Zealand, China and, of course, Israel. In Israel, in the last 4 years, RLT for mCRPC patients with 177Lu-PSMA-I&T is available and approved by the country's Ministry of Health, All major hospitals in Israel are allowed to administer 177Lu-PSMA-I&T RLT and accept medical tourism patients as well. To date, 177Lu-PSMA-617 (PLUVICTO®) is not registered in Israel. On April 24, 2023, the FDA granted Lantheus and POINT Biopharma fast track designation to the prostate specific membrane antigen (PSMA)-targeted therapy, 177-Lu-PSMA-I&T (177-Lu-PNT2002), for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) [13]. Fast track designation by the FDA is an important step that has the potential for 177-Lu-PNT2002 to address the significant unmet needs of mCRPC patients. References
  1. Sartor O, DeBono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, et al., 2021. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New Engl J Med. 385(12):1091–1103. DOI:10.1056/nejmoa2107322
  2. FDA approves first PSMA Radiotherapeutical Treatment of Prostate Cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608311/
  3. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html
  4. https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Lutetium%20Lu%20177%20Vipivotide%20Tetraxetan%20(Pluvicto)%20Injection&st=c
  5. https://edition.cnn.com/2023/03/21/health/pluvicto-prostate-cancer/index.html#:~:text=Pluvicto%2C%20a%20drug%20to%20treat,doses%20to%20treat%20existing%20patients
  6. https://www.novartis.com/us-en/news/radioligand-therapy-supply-information
  7. https://www.novartis.com/sites/novartis_com/files/q1-2023-media-release-en.pdf
  8. Hartrampf, Philipp E., et al. "Matched-pair analysis of [177Lu] Lu-PSMA I&T and [177Lu] Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer." European Journal of Nuclear Medicine and Molecular Imaging9 (2022): 3269-3276.
  9. https://bookinghealth.com/disease/lutetium-177-psma-therapy
  10. https://medicalnewsbulletin.com/best-hospital-for-lutetium-therapy/
  11. https://medsurgeindia.com/nuclear-medicine-therapy/lu-psma/
  12. https://www.thelondonclinic.co.uk/services/treatments/lutetium-177-psma-advanced-prostate-cancer
  13. Lantheus and POINT Biopharma announce FDA grants fast track designation for ¹⁷⁷Lu-PNT2002 for the treatment of metastatic castration resistant prostate cancer. News release. Lantheus and POINT Biopharma. April 24, 2023. Accessed April 25, 2023. https://bit.ly/3ALtKZv