FDA approves expanded access program to provide alternative source of BCG

The FDA has authorized an expanded access program (EAP) to provide an alternative source of BCG, recombinant BCG (rBCG), to patients across the US, ImmunityBio announced in a news release.¹

The rBCG vaccine has been evaluated in phase 1/2 clinical trials in Europe.

According to the company, the hope is that this program will help to address the ongoing shortage of TICE BCG in the US. The shortage, which ramped up in 2019, has posed challenges for the treatment of patients with non–muscle invasive bladder cancer (NMIBC), for which BCG has been the standard of care since 1977. In the release, ImmunityBio cited a recent survey of 100 urologists, of which 57% reported they were unable to treat patients in the previous 12 months due to a lack of access to TICE BCG.

There is currently only one manufacturer of TICE BCG in the US. For this EAP, ImmunityBio has partnered with the Serum Institute of India, which develops rBCG, to provide an alternative source across the country. According to the news release, these shipments are set to begin immediately.

“With the increasing threat of supply shortages of essential medicines, the biopharmaceutical industry must innovate and secure new means of ensuring uninterrupted access to vital therapeutics,” said Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, in the news release.¹ “Our collaboration with the FDA and Serum Institute to ensure a reliable supply of this vital drug for bladder cancer patients underscores ImmunityBio’s commitment to addressing critical access issues that affect so many patients.”

Following the FDA's approval of nogapendekin alfa inbakicept-pmln (Anktiva) in April 2024, ImmunityBio announced the collaboration with the Serum Institute of India to supply the company with standard BCG, as well as rBCG, to be used in combination with Anktiva in its approved indication.² The supply of BCG through this partnership is now available through the EAP across the US.

The rBCG vaccine (VPM1002BC) has been evaluated in phase 1/2 clinical trials in Europe as an immunotherapy in patients with NMIBC.^3,4 According to ImmunityBio, rBCG has 2 gene modifications that enable improved immunogenicity and safety vs other formulations of BCG. In clinical trials, the rBCG vaccine has already shown favorable safety and tolerability as well as enhanced immunogenicity in driving CD8+ and CD4 T cells compared with earlier strains of BCG, the company reported.

Specifically, the phase 1/2 trial of the therapy, conducted in patients with NMIBC who had failed conventional BCG, showed that 49.3% (95% CI, 32.1-64.4%) of patients treated with VPM1002BC remained recurrence-free at 1 year following treatment.⁴ At 2- and 3-year follow-up, the recurrence-free rates were 47.4% (95% CI, 30.4-62.6%) and 43.7% (95% CI 26.9-59.4%), respectively.

The therapy was also found to be safe and generally well tolerated. Grade 1, 2, and 3 treatment-related adverse events occurred in 14.3%, 54.8%, and 4.8% of patients, respectively. No grade 4 adverse events were reported. In total, 2 of 42 patients were not able to complete 5 or more instillations during the induction period.

Data on rBCG is also available from studies assessing it as a tuberculosis (TB) vaccine. These studies include 2 trials in healthy adult participants, 1 in healthy newborn infants, and a trial in HIV-unexposed and HIV-exposed, BCG-naive newborn infants. Studies have also been conducted to assess “the effect of rBCG vaccination on TB recurrence and on the susceptibility or severity of respiratory diseases during the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic,” ImmunityBio noted.

References

1. FDA authorizes ImmunityBio to provide recombinant BCG (rBCG) to urologists to address TICE BCG shortage. News release. ImmunityBio. February 19, 2025. Accessed February 19, 2025. https://ir.immunitybio.com/news-releases/news-release-details/fda-authorizes-immunitybio-provide-recombinant-bcg-rbcg

2. ImmunityBio, Serum Institute of India agree on an exclusive arrangement for global supply of Bacillus Calmette-Guerin (BCG) across all cancer types. News release. ImmunityBio. May 2, 2024. Accessed February 19, 2025. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-serum-institute-india-agree-exclusive-arrangement

3. Rentsch CA, Bosshard P, Mayor G, et al. Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy. Oncoimmunology. 2020;9(1):1748981. doi:10.1080/2162402X.2020.1748981

4. Rentsch CA, Thalmann GN, Lucca I, et al. A phase 1/2 single-arm clinical trial of recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC immunotherapy in non-muscle-invasive bladder cancer recurrence after conventional BCG therapy: SAKK 06/14. Eur Urol Oncol. 2022;5(2):195-202. doi:10.1016/j.euo.2021.12.006