As rival Merck monopolizes BCG supply, ImmunityBio taps Serum Institute for new combo's manufacturing

ImmunityBio last week won the FDA’s approval for its immunotherapy Anktiva to be used alongside the Bacillus Calmette-Guérin (BCG) vaccine to treat certain patients with bladder cancer. Problem is, there is an ongoing global shortage of BCG.

Now, the California biotech has partnered with the Serum Institute of India in an exclusive deal to manufacture BCG globally.

The arrangement aims to create “a long-term solution to chronic BCG supply shortage issues” and produce BCG “at large scale” for use in combination with Anktiva in non-muscle invasive bladder cancer (NMIBC), ImmunityBio said Thursday.

BCG, originally developed as a tuberculosis vaccine, is also a standard treatment for NMIBC, which accounts for about 80% of around 80,000 new bladder cancer diagnoses each year in the U.S.

The FDA has cleared Anktiva and BCG to treat patients with BCG-unresponsive NMIBC with carcinoma in situ. And ImmunityBio is evaluating the combo in BCG-unresponsive NMIBC with papillary tumors and perhaps more importantly in BCG-naïve NMIBC.

In the current indication, ImmunityBio will go toe to toe with Merck & Co.’s PD-1 megablockbuster Keytruda and Ferring Pharmaceuticals’ gene therapy Adstiladrin, both of which are administered by themselves without BCG. Ironically, Merck is currently the sole supplier of BCG in the U.S.

Merck’s TICE BCG has been the lone BCG product in the U.S. since 2012, coming after Sanofi and another drugmaker ran into manufacturing problems. Sanofi officially pulled out of the market in 2016. Merck, which had before then not been the major supplier globally for BCG, was forced to pick up the slack.

In October 2020, Merck announced a plan to construct a new TICE BCG manufacturing facility in North Carolina. But that project was anticipated to be completed by late 2025 to late 2026, according to a Merck update in January this year. Once operational, Merck expects to triple its current BCG capacity and believes believes it will be able to meet demand “for the foreseeable future.”

Merck has been rationing BCG supply since 2019. The New Jersey Big Pharma allocates its limited supply to distributors and wholesalers based on historical purchasing, and it doesn’t directly determine the supply to individual healthcare providers.

SII is the largest manufacturer of BCG vaccine globally, according to ImmunityBio. The Indian company has two BCG products for oncology use, one traditional BCG called Onco-BCG is already commercialized outside the U.S. The new deal will see SII immediately supply that standard BCG for ImmunityBio’s clinical trials once the FDA signs off on the trial protocols, which ImmunityBio plans to submit to global regulatory authorities within 30 days.

The second product, a recombinant BCG, is undergoing midstage testing in Europe. This version includes two gene modifications to improve its profile, and according to ImmunityBio, it has shown “potent immunogenicity with CD8+ and CD4+ stimulation and improved safety compared to standard BCG.” The two partners are now working to speed up the phase 2 program.

However, in both cases, the timeline for commercial supplies remains unclear. ImmunityBio will have more clarity on the timeline once it submits the trial protocols to the FDA, a media aide to the company told Fierce Pharma.

The good news for ImmunityBio? Anktiva’s current U.S. label doesn’t specify or limit the type of BCG the drug can be used with. This allows the company to explore other alternatives to Merck’s TICE BCG, ImmunityBio’s executive chairman, Patrick Soon-Shiong, M.D., said during an investor call last week.

“We are pleased to partner with the Serum Institute of India so that the power of its large-scale, world-class, GMP manufacturing capacity can be used to address the issue of BCG shortage, which affects thousands of bladder cancer patients annually,” Soon-Shiong said in a statement Thursday.

Financial details and the exact terms of the deal were not disclosed.