On August 24, 2023 Royalty Pharma plc (Nasdaq: RPRX) and Ferring Pharmaceuticals reported that Royalty Pharma has acquired a synthetic royalty on US net sales of Ferring’s Adstiladrin (nadofaragene firadenovec-vncg) for up to US $500 million comprised of an upfront payment of US $300 million and a US $200 million milestone payment (Press release, Ferring, AUG 24, 2023, View Source [SID1234634647]). The milestone payment is contingent on certain manufacturing goals that are expected to be achieved in 2025 for the FDA-approved intravesical gene therapy that Ferring will make available next month through an early experience program for the treatment of adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

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Under the terms of the agreement, Royalty Pharma is acquiring a 5.1% percentage royalty on net sales of Adstiladrin in the United States, which will increase to 8.0% upon payment of the manufacturing-related milestone. The royalty is expected to end in the early to mid-2030s.

"This major investment by Royalty Pharma, the largest buyer of biopharmaceutical royalties and a leading funder of innovation, is yet another demonstration of the value and confidence in our gene therapy Adstiladrin to address significant unmet medical needs for patients. It also highlights its significant potential as a key growth driver for Ferring, and our commitment to Uro-Oncology," said Jean-Frédéric Paulsen, Executive Chairman of Ferring Pharmaceuticals.

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 75% of all new bladder cancer cases.[i] Adstiladrin is a non-replicating adenovirus vector-based gene therapy for the treatment of adult patients with high-risk BCG-unresponsive NMIBC. Although BCG remains the first-line standard of care for people living with high-grade NMIBC, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.[ii] In April 2023, the FDA approved a Prior-Approval Supplement (PAS) to the Biologics License Application (BLA) for the therapy which enabled the scale-up of drug substance manufacturing process.

"After several decades of little progress in the field, Adstiladrin brings a major innovation to patients with high-risk NMIBC who no longer respond to current first-line treatment and have few other good options. Our ambition is for Adstiladrin to become the new standard of care and the backbone therapy for these patients and to drive research in other urothelial cancers. This agreement positions us well for continued significant and sustained investment to further advance Adstiladrin as the foundation of our leadership drive in Uro-Oncology," said Bipin Dalmia, Global Head, Uro-Oncology Franchise of Ferring Pharmaceuticals.

"We are delighted to partner with Ferring, a research-driven, global specialty biopharmaceutical company. This investment is consistent with our strategy of acquiring royalties on innovative therapies in areas of high unmet patient need," said Pablo Legorreta, founder and Chief Executive Officer of Royalty Pharma. "Adstiladrin is the first gene therapy in our diversified royalty portfolio. We believe it has blockbuster potential and we are pleased to provide funding to support the launch of Adstiladrin and help Ferring reach as many patients as possible with this important therapy in the United States."

About Adstiladrin
Adstiladrin (nadofaragene firadenovec-vncg) is a gene therapy developed as a treatment for adult patients with BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based gene therapy containing the gene encoding interferon alfa-2b protein, administered by catheter into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the interferon gene. The internal cell machinery translates the interferon DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a recombinant analog of the naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer. Nadofaragene firadenovec-vncg has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).

US FDA approval of Adstiladrin on December 16, 2022 was based on results of the Phase 3 clinical trial, which met its primary endpoint with more than half (51%, n=50 of 98; 95% CI 41 to 61) of patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1) achieving a complete response (CR) by three months. Of the patients who achieved an initial CR, 46% (n=23 of 50) continued to remain free of high-grade recurrence at 12 months.

INDICATION
Adstiladrin is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS: Adstiladrin is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product.

WARNINGS AND PRECAUTIONS:

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
DOSAGE AND ADMINISTRATION: Administer Adstiladrin by intravesical instillation only. Adstiladrin is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during Adstiladrin treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during Adstiladrin treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.