In a stark contrast of regulatory outcomes announced on May 5, Culver City-based ImmunityBio faced a significant setback while Thousand Oaks-based Atara Biotherapeutics received encouraging news from the U.S. Food and Drug Administration.
ImmunityBio disclosed that on May 2, it received a "refusal to file" (RTF) letter from the FDA rejecting its supplemental Biologics License Application (sBLA) for Anktiva. This application sought to expand the drug's use to a broader subset of bladder cancer patients beyond its initial approval last year. Following the announcement, ImmunityBio's stock plummeted 25% over three trading sessions.
ImmunityBio's Regulatory Setback
The rejection represents a significant obstacle in ImmunityBio's expansion strategy for Anktiva, which received its first-ever FDA approval just one year ago for treating a specific subset of bladder cancer patients. That milestone enabled the 10-year-old company to begin marketing the immunotherapy drug and generating its first substantial revenue from drug sales.
According to the FDA's website, an RTF letter "notifies a drug company that FDA will not review a marketing application because of significant deficiencies that cannot promptly be resolved, making the application substantially incomplete." The specific deficiencies cited in ImmunityBio's case were not disclosed, as the FDA does not publicly release the contents of such letters.
Patrick Soon-Shiong, ImmunityBio's billionaire founder and executive chairman, expressed frustration with the decision, stating: "The Agency must explain the confounding inconsistency of approving ANKTIVA+BCG for patients with Papillary with CIS disease, while refusing to file the sBLA for patients with Papillary without CIS disease – even though both groups were part of the same trial."
The rejection is particularly disappointing for ImmunityBio as it would have expanded the eligible pool of bladder cancer patients four-fold. Just last month, the company held an investor day outlining ambitious plans to expand Anktiva's applications, including a variation designed to boost lymphocyte counts in patients with various cancers, which CEO Richard Adcock suggested could become a blockbuster drug.
Atara's Regulatory Relief
In contrast, Atara Biotherapeutics received positive news when the FDA lifted its hold on clinical trials for Ebvallo, a drug developed to treat blood cancers. The agency also granted Atara a meeting date to discuss the path forward for resubmitting Ebvallo for regulatory consideration. This development sent Atara's stock up 6%.
The favorable update follows a challenging period for Atara, which received a "complete response" letter from the FDA in January citing concerns with a third-party manufacturer's compliance with standards. That announcement had triggered a 50% drop in Atara's share price, followed by an FDA hold on all Ebvallo clinical trials.
Unlike ImmunityBio's situation, Atara's regulatory issues appear more straightforward to resolve, as they relate to manufacturing protocols rather than the drug's safety or efficacy profile. Complete response letters are relatively common in the pharmaceutical industry and often involve implementing additional quality control measures with manufacturing partners.
Implications for Both Companies
For ImmunityBio, the RTF letter represents a significant roadblock in its commercialization strategy. The company has publicly called for a meeting with the FDA, arguing that the rejection is inconsistent with both the initial Anktiva approval and recommendations shared by FDA officials during a January meeting with company executives.
The expanded indication would have been crucial for ImmunityBio's growth plans, as it would have substantially increased the addressable patient population. Soon-Shiong emphasized the urgency of reconsidering the decision "on behalf of patients facing a potential loss of a vital organ (the bladder) and high risk of progression of disease."
For Atara, the lifting of the clinical trial hold represents a critical step toward potentially bringing Ebvallo to market. The upcoming meeting with the FDA will address issues raised in the complete response letter and outline the path for resubmission, potentially putting the company back on track toward commercialization.
Regulatory Context
This tale of two FDA decisions highlights the complex and sometimes unpredictable nature of the drug approval process. ImmunityBio itself experienced a complete response letter in late 2023 that delayed Anktiva's initial approval by six months, demonstrating that even successful applications can face temporary setbacks.
The contrasting outcomes for these two Southern California immunotherapy companies underscore the significant impact regulatory decisions can have on biotechnology firms' trajectories, particularly for companies with limited or no marketed products. For ImmunityBio, which received its first-ever approval just last year, expanding Anktiva's indications represents a critical growth strategy. For Atara, resolving manufacturing issues is essential to advance its lead candidate toward potential approval.
As both companies navigate their respective regulatory paths forward, the outcomes will have significant implications not only for their business prospects but also for patients awaiting additional treatment options for bladder cancer and blood cancers.
