First Approval Bodes Well For Hanmi’s Olmutinib

SEOUL - Hanmi Pharmaceutical Co. Ltd.’s novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor (TKI), olmutinib (HM61713/BI 1482694), has received an approval for lung cancer from South Korea’s Ministry of Food and Drug Safety (MFDS), paving the way for the drug to debut in this market ahead of its main competitor Tagrisso.

Hanmi expects to roll out the oral drug as Olita later this year, when it will become the first TKI therapy approved in the country for EGFR T790M mutation-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC). The company declined to comment on details of the launch, including whether it will be reimbursed.

Olmutinib will be used in patients who have previously been administered EGFR TKIs such as AstraZeneca PLC‘s Iressa (gefitinib) and Roche‘s Tarceva (erlotinib), and becomes South Korea’s 27th novel, domestically developed drug.

The MFDS approved Olita using a fast-track approval system under which regulatory clearance is granted to an innovative drug based on Phase II data if safety and efficacy are confirmed, and on condition Phase III trials are conducted after launch. The drug has to be indicated for life-threatening diseases or without alternative drugs.

The ministry said it expects Olita to provide “a new treatment opportunity for NSCLC patients who have shown resistance to existing lung cancer therapies and don’t have proper treatment options,” and a breakthrough therapy designation has already been granted by the US FDA.

In July last year, Boehringer Ingelheim GMBH and Hanmi signed an exclusive license and collaboration agreement for global development and global commercialization rights to olmutinib, excluding South Korea, China and Hong Kong (Also see "Hanmi Inks Record Korean Deal, With Boehringer For Cancer Therapy" - Scrip, 28 Jul, 2015.).

In November, Hanmi then licensed out rights in China, Hong Kong and Macau to China’s ZAI Lab Ltd. (Also see "Hanmi’s Roll Continues With ZAI China Cancer Deal" - Scrip, 23 Nov, 2015.).

The MFDS gave the green light for a local Phase III trial of AstraZeneca’s Tagrisso (AZD9291) in February. The drug received the US FDA’s regulatory approval in November last year, becoming the first approved medicine indicated for patients with metastatic EGFR T790M mutation-positive NSCLC.

Positive Clinical Results

Results from the Phase I/II HM-EMSI-101 clinical trial with olmutinib, presented at the ESMO Asia 2015 Congress in Singapore and previously presented at the American Society of Clinical Oncology (ASCO) annual meeting, showed antitumor activity and a favorable safety profile at the recommended Phase II dose of 800mg once daily.

In the 69 patients, objective responses (ORs) by independent assessment were observed in 62% patients, including 32 patients (46%) whose tumor response had been confirmed by the time of data cut-off. Disease control rate was 91% by independent assessment. At the time of data cut off, median duration of response had not yet been reached and will be reported at a later date.

The majority of treatment-related adverse events were mild to moderate and included diarrhea, nausea, rash and skin itching.

Boehringer, which is conducting the ongoing pivotal Phase II ELUXA 1 global clinical program, plans to carry out various accelerated studies and global Phase III trials this year, aiming to receive the first approvals in 2017. The first data are expected to be submitted to the US FDA and EU EMA this year.

Growing Market

Datamonitor Healthcare expects the NSCLC market to nearly triple in total sales terms over the next 10 years. Using a patient-based forecasting methodology, it estimates that sales of key NSCLC drugs across the US, Japan, and five major EU markets (France, Germany, Italy, Spain, and the UK) totaled $6,659m in 2014.

The combined value of these markets is expected to increase to $17,609m in 2023, with an overall compound annual growth rate of 11.4%.

The primary drivers for this growth include an increasing incidence of NSCLC in all markets, the introduction of costly immunotherapies into treatment, and the launch of next-generation targeted therapies for patients who acquire resistance.

Third-generation EGFR inhibitors will give patients who acquire resistance to first-line targeted agents additional personalized options to utilize in later lines of therapy. Furthermore, these treatments have also shown the potential to improve upon the efficacy of class leaders and are expected to gain uptake in previously untreated patients, Datamonitor notes.

Commitment To Innovation

The approval of olmutinib through South Korea’s fast-track system brought forward the drug’s launch by around two years, and underscores the country’s ongoing efforts to support the development of innovative, domestically developed medicines.

The clearance was described by Professor Keunchil Park of the Samsung Medical Center in Seoul as “a great step forward” for the majority of mutation-positive NSCLC patients in South Korea who have the “devastating development” of becoming resistant to previous treatment. Boehringer’s oncology head Dr. Jörg Barth said the first approval of the drug globally was “an exciting milestone.”

The number of MFDS approvals for novel South Korea-developed drugs rose to five items in 2015, from just one in 2014, while approvals of orphan drugs surged to 49 products from 28. The industry’s strong interest in orphans and the government’s increased support for domestically developed novel drugs are contributing to the rising trend.

Earlier this year, the government said it plans to draw up detailed guidelines for a fast-track review and approval system this year to increase applications for such treatment, provide the pharma industry with a clearer understanding of the process, and to provide timely patient access to more treatment options (Also see "Korea To Bolster Fast-Track System With Speedier Approvals In Mind" - Scrip, 2 May, 2016.).