pharm edaily

[Kim Saemi, Edaily Reporter] HLB Group’s hopes for FDA approval of its liver cancer treatment, Rivoceranib, were dashed again after receiving a second complete response letter(CRL) from the U.S. Food and Drug Administration. The decision marks the second rejection in less than a year, following a similar notice in May 2024.

HLB Group Chairman Jin Yang-gon (center) holds an emergency YouTube press conference at 9 a.m. on the 21st to explain the current situation. (Source = HLB press conference YouTube)

Despite the setback, the company said it will resubmit its new drug application(NDA) in May, with a goal of receiving FDA approval by July. It also plans to submit a marketing authorization application to the European Medicines Agency in July, and file an NDA later this year for lirafugratinib, its bile duct cancer candidate.

Stock Plunge Follows Second FDA Rejection

At 3 a.m. on March 21st, HLB Chairman Jin Yang-gon said via YouTube that the company had received another CRL from the FDA, this time citing unresolved chemistry, manufacturing and controls(CMC) issues related to partner Jiangsu Hengrui Pharma.

The drug combination of Rivoceranib and camrelizumab, developed with Hengrui, is being evaluated for first-line treatment of liver cancer.

HLB shares tumbled on the news, falling 29.97% to 46,500 won in morning trading. And HLB Life Science dropped 29.94%, HLB Pharma fell 29.92%. Most other HLB affiliates also traded sharply lower.

HLB stocks have previously been volatile. In May 2023, the first CRL sent nine HLB-related companies to their lower trading limits, wiping out more than 5 trillion won ($3.7 billion) in market capitalization in a single day.

In 2019, HLB also saw a steep decline after announcing its Phase 3 gastric cancer trial had failed to meet its primary endpoint, rattling the broader KOSDAQ market.

HLB Confident in Class 1 Review, July Decision

In an emergency briefing on March 21st morning, HLB said it would resubmit its NDA by May and expected a decision by July, assuming a Class 1 review.

Jin said the latest CRL stemmed from “CMC issues that Hengrui has yet to fully resolve.” He added that once Hengrui contacts the FDA, it will receive more detailed instructions for corrective action.

“We believe it will still be a Class 1 review, which typically takes two months,” Jin said. “Even in the worst case, we expect it not to exceed that timeline.”

FDA resubmissions are classified as either Class 1 (minor revisions, two-month review) or Class 2 (major changes, six-month review with possible reinspection).

Although HLB anticipated a Class 1 review last year, the FDA assigned the resubmission to Class 2. This time, Jin said, circumstances are different. “The first CRL included 10 findings related to camrelizumab’s CMC and clinical inspections. This time, there are only three, and they are clear and addressable.”

The three new issues include: A sterilization protocol to prevent microbial contamination, Procedures for visual inspection, Regular inspection of automated and computerized systems.

EMA Filing Coming in July, NDA for Lirafugratinib by Year-End

By July this year, HLB will apply to the European Medicines Agency (EMA) for product approval for combination therapy of riboceranib and camrelizumab for liver cancer treatment. The company said most of the preparations for this have already been completed. However, after the meeting, the company said that the submission of the application for product approval to the EMA could actually take place in September this year.

HLB also plans to file an NDA for lirafugratinib, a second-line treatment for bile duct cancer, in the second half of 2024. The drug was licensed from U.S.-based Relay Therapeutics in December 2023 for up to $500 million, including a $5 million upfront payment.

Because lirafugratinib has received FDA breakthrough therapy designation and completed global Phase 2 trials, HLB said it may pursue conditional approval with a post-marketing Phase 3 trial.

Focus Remains on Liver Cancer Approval

HLB said it will not seek approval for other indications at this time, including gastric cancer or paraganglioma. Instead, the company will focus its regulatory strategy on the liver cancer indication.

“Fast reapproval for liver cancer is the most efficient strategy in terms of cost and timeline,” Jin said.

He explained that Rivoceranib’s patent expires in 2034, making standalone treatment less commercially viable. “We’re focused on combination therapy not because monotherapy is ineffective, but because the data shows greater efficacy in combination,” he said.

HLB still plans to include Rivoceranib in the NCCN guidelines for Adenoid Cystic Carcinoma(ACC) , but said it has no current plans to pursue an FDA application for that indication.

“There was talk of using ACC for FDA approval, but the priority now is liver cancer,” Jin said.

Jin closed by noting that many companies have received FDA approval after two CRLs, adding, “We’ll do our best to achieve reapproval quickly.”

He said the company would simultaneously move forward with the EMA application and NDA for bile duct cancer, urging stakeholders to be patient.

“Just give us a little more time,” he said. “We’ll deliver results.”