Rivoceranib Approval Delayed
FDA Delays HLB's Rivoceranib Approval for Third Time Citing Persistent Manufacturing Deficiencies
Anonymous
Key Points
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The latest FDA CRL notes a Form 483 issued after a routine cGMP inspection of the listed manufacturing facility, and the agency will not approve rivoceranib until the cGMP deficiencies are resolved and confirmed by inspection; a Pre-Approval Inspection may follow if needed.
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The facility has not been inspected by the FDA for eight years; in its previous five inspections since 2018, it received four 'No Action Indicated' (NAI) ratings and one 'Voluntary Action Indicated' (VAI) rating.
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This is rivoceranib's third CRL; the earlier CRLs were issued in May 2024 and March 2025 and were tied to chemistry, manufacturing and controls issues at camrelizumab manufacturing and related quality-control concerns, with COVID-19-related monitoring disruptions noted in the past.
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HLB's stock in Korea fell about 30% to the daily lower limit, trading around 36,600 won and approaching a 52-week low, as investors reacted to the FDA setback and awaited next steps.
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HLB previously acquired Elevar Therapeutics in 2021; Elevar is responsible for the U.S. development of rivoceranib, including its NDA review in combination with camrelizumab.
HLB and its U.S. partner Elevar Therapeutics have received a third Complete Response Letter (CRL) from the FDA, again blocking approval of their liver cancer drug rivoceranib. The latest rejection, reported on May 10, stems from manufacturing quality issues at the drug's production facility — not from clinical data problems. Korea Economic Daily reported HLB shares collapsed to their daily limit-down of about 30%, falling to roughly 36,600 won and approaching a 52-week low.
This marks the third straight CRL for rivoceranib, which is being reviewed in combination with the cancer drug camrelizumab for hepatocellular carcinoma, the most common form of liver cancer. Each rejection has been tied to chemistry, manufacturing, and controls (CMC) issues — not the drug's effectiveness.
Third Manufacturing Rejection Tied to cGMP Inspection Failures
The FDA issued a Form 483 — a formal list of observed violations — after a routine inspection of the listed drug manufacturing facility. The agency uses current Good Manufacturing Practice (cGMP) rules to ensure drugs are made safely and consistently. Until those violations are fixed and confirmed by a follow-up inspection, the FDA will not approve rivoceranib. A Pre-Approval Inspection may also be required before any final green light.
The facility had not been inspected by the FDA in eight years. Despite that long gap, its track record was solid: in five inspections since 2018, it received four 'No Action Indicated' (NAI) ratings — the FDA's best outcome — and one 'Voluntary Action Indicated' (VAI) rating. The latest inspection broke that streak, catching deficiencies serious enough to trigger a full CRL.
A Pattern of Setbacks: Three CRLs in Under Two Years
The FDA first rejected rivoceranib in May 2024, then again in March 2025. Both earlier CRLs pointed to CMC issues at the camrelizumab manufacturing site, along with quality-control concerns. COVID-19-related monitoring disruptions were also cited in past rejections as a complicating factor. The Chinese manufacturers involved have been identified in various reports as either Hansoh Pharma or Hengrui.
Each time, HLB said it would work with manufacturers to fix the problems and refile. The company has repeated that pledge following this third CRL. But three consecutive manufacturing-linked rejections signal deep, unresolved compliance challenges — ones the FDA will not overlook regardless of how strong the clinical data may be.
HLB Shares Crater as Investors Lose Patience
The market's reaction in South Korea was immediate and severe. Seoul Daily reported that HLB shares, listed on KOSDAQ under ticker 028300, hit the daily limit-down — a 30% drop — falling to around 36,600 won. That puts the stock near its 52-week low. Other HLB Group companies also fell sharply on the news.
Investor frustration is mounting. HLB acquired Elevar Therapeutics in 2021, betting heavily on rivoceranib as its flagship U.S. drug. Elevar leads the NDA review process in America. After three failed attempts in less than two years, shareholders are watching closely to see whether HLB can finally resolve the manufacturing problems and get a fourth submission across the finish line.
What Comes Next: Refiling Hinges on Factory Fix
HLB says it plans to refile the application once the manufacturing deficiencies are corrected. The FDA must then confirm the fixes through an inspection before moving forward. If the agency is satisfied, it may still require a Pre-Approval Inspection as a final check. That process could take months, pushing any potential U.S. launch further into the future.
Rivoceranib has shown strong clinical results for liver cancer patients, making the repeated manufacturing stumbles especially frustrating for HLB and patient advocates. The drug's path to U.S. approval now depends entirely on whether the Chinese production facility can meet FDA standards — and pass inspection on the next try.
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