Who Comes After 'Rolenitis'? ... Who Will Be the 7th FDA New Drug?

Hanmi Pharm's 'Rolontis' Approval Increases FDA New Drugs to Six

Hanmi's 'Poziotinib'·Yuhan's 'Reclaza'
HLB's 'Liboceranib'·Green Cross's 'Aliglo' Awaiting Approval

Poziotinib Expected for Approval This Year but Advisory Committee Gave Negative Opinion
Reclaza, Janssen Expects Over 7 Trillion KRW Sales, Likely to Apply for Approval Next Year
Liboceranib Achieves Record-Breaking Results in Combination Therapy
Aliglo Delayed Due to COVID-19 Inspections... "Expecting Schedule Confirmation Within the Year"

Rolontis, Hanmi Pharmaceutical's neutropenia treatment, the sixth Korean new drug to receive approval from the U.S. Food and Drug Administration (FDA)

[Asia Economy Reporter Lee Chun-hee] Hanmi Pharmaceutical's neutropenia treatment 'Rolontis' has received approval from the U.S. Food and Drug Administration (FDA), drawing attention to who will be the next in line.

According to the industry on the 27th, with Rolontis receiving FDA approval, the total number of Korean new drugs approved by the FDA has increased to six. Since LG Chem's antibiotic 'Pactiv' was the first to receive FDA marketing approval in 2003, the list includes ▲Dong-A ST's 'Cibextro' (2014) ▲SK Chemicals' 'Abstila' (2016) ▲SK Biopharm's 'Sunosi' and 'Xcopri' (2019). Although there was a hiatus afterward, Rolontis' approval marks the birth of a new FDA-approved drug after three years.

Naturally, the industry's focus is now on who will next cross the FDA approval threshold. Currently, Hanmi Pharmaceutical's non-small cell lung cancer treatment 'Poziotinib', Yuhan Corporation's non-small cell lung cancer treatment 'Reclaza' (generic name: Lazertinib), HLB's anticancer drug 'Rivoceranib', and GC Green Cross's new immunoglobulin drug 'Aliglo' are competing fiercely.

Poziotinib, aiming to be the 7th FDA new drug... Advisory committee says "Risks > Benefits"

Initially, Poziotinib was the most likely next candidate. It is currently the only Korean new drug with a Prescription Drug User Fee Act (PDUFA) decision deadline set for November 24. This raised expectations that Hanmi Pharmaceutical could achieve FDA approval for the second consecutive time.

However, at the FDA's Oncology Drugs Advisory Committee (ODAC) meeting held on the 22nd-23rd (local time), the committee judged that the benefits of Poziotinib do not outweigh the risks, casting a red light on its approval prospects. ODAC is an independent advisory committee composed of experts who review and evaluate data on the efficacy and safety of anticancer drugs.

In related materials released before the ODAC meeting, the committee strongly expressed concerns about Poziotinib's efficacy, stating, "If granted accelerated approval, this would be the least effective targeted therapy for lung cancer approved to date."

Exterior view of Hanmi Pharmaceutical headquarters

ODAC questioned Poziotinib's efficacy, citing an objective response rate (ORR)?the proportion of patients showing tumor size reduction or other objective responses?of about 28%, which is low. They directly compared this to AstraZeneca-Daiichi Sankyo's antibody-drug conjugate (ADC) anticancer new drug 'Enhertu' (generic name: Trastuzumab Deruxtecan), recently approved in Korea, which has an ORR of 58%. They also pointed out that the median duration of response (mDoR) for Poziotinib is 5.1 months, lower than Enhertu's 8.7 months.

ODAC also viewed safety concerns as significant. Among 368 patients receiving 16 mg once daily of Poziotinib, 85% experienced grade 3-4 adverse events, and 57% required dose reductions, indicating a low drug tolerance in terms of safety profile. While the advisory committee noted that such side effects might be mitigated in alternative dosing groups, they emphasized the need for further analysis regarding the efficacy at the current dose.

However, some in the industry predict that although the timeline may be delayed, Poziotinib's approval itself is still possible. While accelerated approval may be difficult, the advantage of an oral formulation is significant, and Poziotinib may have higher efficacy against the 'exon 20' mutation it targets compared to drugs like Enhertu, so FDA approval is not considered impossible. Hanmi Pharmaceutical also emphasized, "Lung cancer has a much higher mortality rate compared to other cancers, so patients should be provided with various treatment options. Poziotinib is clearly useful as a second- or third-line treatment for patients unresponsive to existing therapies, and it offers dosing convenience as an oral drug rather than intravenous (IV) administration."

Reclaza, Rivoceranib, and Aliglo making advances

Yuhan Corporation's non-small cell lung cancer treatment 'Reclaza'

Yuhan Corporation's non-small cell lung cancer treatment Reclaza was initially expected to be approved within the year, but it is now anticipated to submit an FDA approval application sometime next year. Considering ongoing combination clinical trials with Janssen's bispecific antibody 'Amivantamab', which received FDA approval last year, submission is likely to occur next year.

Reclaza has already been approved domestically, achieving commercial success with cumulative sales exceeding 10 billion KRW. At Janssen, CEO Joaquin Duato has identified the combination therapy of Lazertinib and Amivantamab as one of the top five major pipelines expected to generate over 5 billion USD (approximately 7 trillion KRW) in sales, indicating significant expectations from Janssen as well.

On the 10th (local time), the results of the Phase 3 clinical trial of the combination therapy of 'Rivoceranib' and 'Camrelizumab' were announced at the 2022 European Society for Medical Oncology (ESMO) held in Paris, France.

HLB's Rivoceranib, which recently announced innovative results through combination therapy with Anti-Cancer Pharmaceutical's 'Camrelizumab' for unresectable hepatocellular carcinoma (uHCC) at the European Society for Medical Oncology (ESMO), is also gaining momentum for FDA approval. Since June 2019, HLB has conducted combination therapy clinical trials involving 543 patients across 13 countries including the U.S., Europe, and Asia, achieving a median overall survival (mOS) of 22.1 months?the first time an mOS exceeded 20 months for liver cancer treatments.

Previously, Bayer's Nexavar and Eisai's 'Lenvima' (generic name: Lenvatinib) were considered standard treatments for first-line liver cancer therapy, with OS around 12-13 months. Recently, Roche's combination therapy of 'Tecentriq' (generic name: Atezolizumab) and 'Avastin' (generic name: Bevacizumab) has emerged as a new standard with a 19.2-month OS. However, since Rivoceranib has succeeded in surpassing these results, expectations are rising that it will establish itself as the 'best in class' drug in the liver cancer treatment market.

Based on these results, HLB plans to apply for FDA approval of the combination therapy in the first quarter of next year. They also plan to submit a New Drug Application (NDA) for monotherapy for liver cancer. At the American Society of Clinical Oncology (ASCO) meeting in June, the Korean-American phase 2 clinical trial results showed that 15.1% of patients had a tumor size reduction of over 30% according to the Response Evaluation Criteria in Solid Tumors (Recist v1.1).

GC Green Cross is also preparing to reapply for FDA approval of its new immunoglobulin drug 'Aliglo' 10%. The approval decision deadline was originally set for February, but due to the COVID-19 pandemic and other factors, the production facility inspection could not be conducted, leading GC Green Cross to receive a Complete Response Letter (CRL).

A GC Green Cross official stated, "We are continuously coordinating with the FDA to schedule the production facility inspection and expect the schedule to be finalized within the year."