Ferring Pharmaceuticals Receives U.S. FDA Approval of Drug Substance Manufacturing Scale-up Process for Gene Therapy ADSTILADRIN® (nadofaragene firadenovec-vncg)

PARSIPPANY, N.J.–()–Ferring Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) approved a Prior-Approval Supplement (PAS) to the Biologics License Application (BLA) for the novel intravesical gene-therapy ADSTILADRIN® (nadofaragene firadenovec-vncg), enabling the Company to scale-up its drug substance manufacturing process at FinVector Oy located in Kuopio, Finland. Supplies from the scale-up process manufactured at FinVector’s FDA-approved facility will be available as part of the planned product launch.

“The FDA approval of this supplement is an important step in our manufacturing scale-up which highlights our continued commitment to bring ADSTILADRIN to the community and in helping patients who are suffering from non-muscle invasive bladder cancer,” said Brent Ragans, U.S. President, Ferring Pharmaceuticals.

In May 2022, FinVector started construction of a new facility in Kuopio, Finland which will be one of the world’s largest viral vector manufacturing sites. FinVector is a world leader in development and manufacturing of viral-based gene therapy products. A separate facility dedicated to ADSTILADRIN is under construction within Ferring’s FDA-approved manufacturing site at the Parsippany, New Jersey campus and will add near-term drug product capacity.

“Viral-based gene therapies like ADSTILADRIN have great potential for the treatment of severe diseases, including cancers where there is a high unmet patient need,” said Giuseppe Carloni, Board Member, FinVector. “Our long-established depth of expertise positions FinVector to remain at the forefront of pioneering the development and manufacture of new precision medicines.”

ADSTILADRIN was approved by the FDA in December 2022 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. As the first and only FDA-approved intravesical gene therapy for these patients, ADSTILADRIN provides a potentially transformational alternative to invasive bladder removal surgery.

Ferring remains on track to start making ADSTILADRIN initially available as part of a focused rollout in the United States in the second half of 2023, with supplies increasing in 2024.

About ADSTILADRIN

ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy 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. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN 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).1

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 20223, 75% of which present as NMIBC.4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, 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.2 Current treatment options for BCG-unresponsive patients are very limited, and often result in a highly invasive life-changing procedure of radical cystectomy (complete removal of the bladder).5

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 prior hypersensitivity reactions to interferon alfa or to 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.

About Ferring Pharmaceuticals

Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, uro-oncology and in specialty areas within gastroenterology, including microbiome therapeutics, and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464) or visit www.ferringusa.com.

Learn more at www.ferringusa.com, or connect with us on Twitter, Facebook, LinkedIn, and YouTube.

About FinVector Oy

FinVector is a fast-growing and internationally renowned biopharmaceutical company that manufactures viral-based gene therapy products. As a pioneer in this field, FinVector has extensive experience in cGMP manufacturing. The company’s operations are centered in Kuopio, Finland, and it employs hundreds of highly qualified professionals from over 40 different countries. FinVector works on cutting-edge biopharmaceuticals and has invested in building state-of-the-art GMP facilities for Viral Vector platforms. FinVector is a subsidiary of Ferring Ventures S.A.

References

  1. ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. https://clinicaltrials.gov/ct2/show/NCT02773849.
  2. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17.
  3. American Cancer Society. Key Statistics for Bladder Cancer. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Updated January 12,2022. Accessed November 22, 2022.
  4. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-41.
  5. NCCN Guideline Insights. Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw. 2022;20(8):866–878.

 

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