Novartis Korea's prostate cancer drug Pluvicto, which has been in the spotlight since its approval by the Ministry of Food and Drug Safety, is gaining further attention as the company prepares to administer the first dose to patients in Korea.

Pluvicto is a blockbuster drug that generated more than KRW 1 trillion in global sales last year and is considered to have ushered in the era of so-called ‘radiopharmaceutical missiles’ in oncology.

# Unlike Bayer's Xofigo, which was licensed as a radioactive therapeutic agent in 2014 but was ignored by the market, Pluvicto opened a new era making noteworthy performance.

As a result, global pharmaceutical companies are rushing to develop radiopharmaceuticals after witnessing the success, intensifying competition among domestic pharmaceutical and biotech companies.

According to the medical and pharmaceutical industry on the 27th, the first patient is expected to be treated at one of the largest general hospitals in Korea in late August, after the Ministry of Food and Drug Safety’s approval of Novartis Korea's prostate cancer drug Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in late May.

Pluvicto is a radioligand therapy that binds the radioactive isotope lutetium (177Lu) to prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer, to kill cancer cells. The treatment was acquired by Novartis through its acquisition of US-based Endocyte in 2018.
                                                   
Radioligands are therapeutic agents that combine a therapeutic radioisotope with a ligand (which targets specific cancer cells). When the radioligand binds to the target cell, it releases the therapeutic radioisotope, inhibiting cancer cell proliferation.

Its May approval was based on the Phase III VISION trial. The trial evaluated the efficacy and safety of Pluvicto versus standard-of-care monotherapy in 831 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

Results showed that the the primary endpoint of radiologic progression-free survival (rPFS) was 8.7 months in the Pluvicto arm, which was longer compared to 3.4 months in the control arm. Median overall survival (OS) was 15.3 months in the Pluvicto arm and 11.3 months in the control arm. The risk of radiographic progression or death was reduced by 60% with the use of Pluvicto.

Since the drug was approved by the MFDS, Novartis Korea has been working to start treating patients at the largest hospitals in Korea. In order for medical institutions to introduce the radiopharmaceutical Pluvicto, the institutions need to have a PSMA PET-CT dedicated to prostate cancer and have a separate room for dispensing, quality control, and patient administration of radioactive therapeutic agents.

Currently, 15 medical institutions nationwide, including the largest hospitals in Korea, are equipped with PSMA PET-CT for testing.

Novartis is currently in discussions with 11 of these medical institutions, including Asan Medical Center in Seoul, to provide Pluvicto to prostate cancer patients.

With the first patient expected to be treated without reimbursement as early as August, Novartis Korea is considering introducing a patient program to address the high price of the drug. For reference, the recommended dose of Pluvicto is 7.4 GBq (200 mCi), administered intravenously up to 6 times every 6 weeks (±1 week), and it is expected that tens of millions of won will be spent per dose without reimbursement in clinical sites.

"From the HCP’s point of view, we believe the introduction of Pluvicto will have a positive impact in that it increases the number of weapons available for prostate cancer, and is a proven treatment with no significant side effects," said Dr. In-Keun Park, Professor of Oncology at Asan Medical Center. "The problem is that it is expensive and there are only a limited number of institutions that can perform PSMA PET-CT, rendering its administration equally limited."

"Because it is a radioactive therapeutic agent, it requires a separate space for its administration rather than a general hospital room. Like Kymriah, Pluvicto is also produced through pre-orders," said a representative from Novartis Korea, "So it takes a considerable process to produce the drug in Europe and deliver it to patients in Korea."

"We are reviewing the possibility of introducing a patient program. However, due to the nature of radioactive therapeutic agents, it is quite expensive. This is because it utilizes lutetium, a radioactive isotope," the representative added, "We are also discussing the possibility of applying for insurance reimbursement."

With the use of Pluvicto nearing on-site, the competition among domestic pharmaceutical and biotech companies to develop radiopharmaceuticals is also heating up.

Currently, FutureChem is at the forefront in the area. In mid-May, FutureChem began dosing its first patient in the U.S. for a Phase IIa clinical trial of FC705, a prostate cancer drug for castration-resistant metastatic patients.

FC705 is a radiopharmaceutical that targets PSMA, which is overexpressed on the surface of prostate cancer cells. It kills cancer cells by introducing a therapeutic isotope into a peptide that binds to the PSMA protein.

In a Phase I clinical trial, an objective response rate (ORR) and disease control rate (DCR) were confirmed in all patients who were administered FC705. In addition to the U.S. clinical trial, FutureChem is also conducting Phase II in Korea, including at Seoul St. Mary's Hospital, and is reportedly discussing technology transfer negotiations with China.

In addition, AbTis, a subsidiary of Dong-A ST, is working with CellBion to develop a new radiopharmaceutical. The two companies signed a joint development agreement last month and will utilize AbTis’ linker platform technology AbClick and CellBion's radiopharmaceutical lab linker technology to develop a new Antibody-Radionuclide Conjugate (ARC) drug targeting stomach and pancreatic cancer.

Recently, SK Biopharmaceuticalsentered into a license-in technology transfer agreement with Full-Life Technologies to acquire global development and commercialization rights to FL-091, a radiopharmaceutical candidate targeting neurotensin receptor 1 (NTSR1), from Full-Life Technologies.

FL-091 small-molecule radioligand vector designed to deliver actinium-225 (225Ac), a next-generation radioisotope capable of killing cancer cells by selectively binding to NTSR1, a receptor protein, which is selectively overexpressed in various types of solid tumors, including colorectal cancer, prostate cancer, and pancreatic cancer.

SK Biopharm has been discussing introducing radiopharmaceuticals into its pipeline since last year as the next step after its epilepsy drug cenobamate (U.S. brand name: Xcopri). The company acquired global-level Targeted Protein Degradation (TPD) technology through the acquisition of ProteoVant Sciences last year.

The TPD technology seeks to overcome the limitations of existing therapeutics by degrading and removing target proteins and solving the causes of diseases.

"This license agreement is the most concrete achievement we have made since the announcement of our entry into the field of radiopharmaceutical therapeutics last year," said Dong-hoon Lee, CEO of SK Biopharmaceuticals. "We plan to unveil a more specific business plan for the entire radiopharmaceutical business this year and accelerate clinical development and commercialization."