Patrick Soon-Shiong's ImmunityBio bags FDA approval for Anktiva to challenge Merck in bladder cancer

After a merger and an FDA rejection, celebrity businessman and biotech entrepreneur Patrick Soon-Shiong’s ImmunityBio has landed the company’s first U.S. approval in the cancer immunotherapy Anktiva.

Anktiva, which is an interleukin-15 superagonist, is now cleared by the FDA alongside the Bacillus Calmette-Guérin (BCG) vaccine to treat patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS),  ImmunityBio said Monday.

The drug will now compete with Merck & Co.’s PD-1 inhibitor Keytruda and Ferring Pharmaceuticals’ gene therapy Adstiladrin in the same NMIBC CIS setting regardless of the presence of papillary tumors. Both Anktiva and Adstiladrin are administered directly into the bladder, while Keytruda comes as an intravenous therapy.

Pharma data intelligence outlet Evaluate recently listed Anktiva among the top 10 drug launches expected this year, pegging the immunotherapy could reach nearly $900 million in 2028 sales.

Anktiva’s edge, to hear ImmunityBio’s executive chair Soon-Shiong and CEO Richard Adcock tell it, lies in its ability to induce “durable complete remission.”

In cohort A of the pivotal QUILT-3.032 trial, 58 of 82 patients with high-risk, BCG-unresponsive NMIBC with CIS who took the Anktiva-BCG combo had no measurable tumors after a median follow-up of about two years. The complete response rate was therefore 71%, and the median duration of complete response was 26.6 months, according to data published in NEJM Evidence in late 2022.

Despite the clinical data, the FDA in May 2023 rejected Anktiva, also known as N-803. The agency’s complete response letter cited deficiencies found during a preapproval inspection at ImmunityBio’s third-party manufacturing contractor. The FDA also provided recommendations related to additional chemistry, manufacturing and control issues and assays. Additionally, the FDA requested updated duration of response data in the company’s future resubmission.

Now, after a longer follow-up, the Anktiva-BCG combo’s complete response rate for the 77 evaluable patients was 62%, according to ImmunityBio. By the time of the November 2023 data cutoff, the longest duration of complete response was more than 47 months and remained ongoing, the company said. Among the complete responders, 58% had their responses lasting for at least a year and 40% for at least two years.

Soon-Shiong will present further updates of the QUILT-3.032 study at the upcoming American Urological Association’s annual conference next week.

By comparison, in the KEYNOTE-057 trial that got Keytruda its NMIBC approval in early 2020, Keytruda induced a complete response rate of 41%. Among the 39 patients who achieved a complete response, the median duration of response was 16.2 months.

As for Ferring’s Adstiladrin, a phase 3 trial showed the quarterly gene therapy induced complete responses in 51% of patients by three months. Among the complete responders, 46% remained free of high-grade recurrence at 12 months.

Soon-Shiong, a partial owner of the Los Angeles Lakers, said Anktiva represents the first validation of what he called the “triangle offense” of an immune response, borrowing a basketball term.

“This will be the first next-generation immunotherapy that goes beyond [killer] T cells and now activates natural killer cells, [and] most importantly, CD8+ memory T cells,” Soon-Shiong said in an interview with Fierce Pharma ahead of the approval.

Those memory T cells, spawned by the activation of CD4+ helper T cells, are critical for Anktiva’s long duration of response, Soon-Siong said. And this “durable complete remission” will be ImmunityBio’s key message to doctors, Adcock said.

Keytruda recently made a splash in its combination with Pfizer and Astellas’ antibody-drug conjugate (ADC) Padcev in metastatic bladder cancer. Pfizer’s plan for Padcev currently doesn’t include NMIBC. And Soon-Shiong, pointing to the “triangle offense,” said he isn’t worried about ADCs, which are essentially cytotoxic chemotherapy with a tumor-directed guide.

“If you give too much toxic drugs, even locally, you wipe out the natural killer cells, which is quite the opposite of what we’re trying to achieve,” he said.

In another feature that could appeal to doctors, the treatment workflow remains almost identical to existing practice with the only extra step being mixing Anktiva together with BCG, Adcock said, who called Anktiva “the least disruptive thing” in terms of workflow.

ImmunityBio believes Anktiva will largely be prescribed by urologists or specialized urologic oncologists. The company has assembled a commercial team of about 60 people, including a sales force responsible for five regional markets and staffers for market access and reimbursement, Adcock told Fierce Pharma. The company expects to make Anktiva commercially available in the U.S. by mid-May.

The CDMO contractor will still be responsible for manufacturing the IL-15 drug thanks to a long-term contract, Adcock said. But ImmunityBio has started to build its own manufacturing capacity to hopefully bring production internally for its pipeline and maybe one day for Anktiva, too.

Anktiva is the backbone of ImmunityBio’s portfolio, Adcock noted. Currently, the California biotech’s entire pipeline is either testing Anktiva alone or in combinations across multiple tumor types and HIV.

Some of the clinical efforts include expanding Anktiva to a larger BCG-unresponsive NMIBC population with high-grade papillary disease. About 90% of NMIBC cases are papillary. This patient group was tested in cohort B of the QUILT-3.032 trial. But because that cohort evaluated disease-free survival, a time-to-event endpoint, the FDA told ImmunityBio that a randomized trial is required to seek an approval there.

ImmunityBio has yet to finalize a registrational trial plan with the FDA in that papillary disease population, Soon-Shiong said. Still, Adcock said “the one to look at” is in the treatment-naïve setting, for which Anktiva is currently in phase 2.

The ImmunityBio we know today was formed through the 2021 merger of two of Soon-Shiong’s “Nant” family of companies, NantKwest and NantCell.