Hanmi to turn efpeglenatide crisis around with new partner

Competitiveness falters as oral GLP-1 agonist released recently

Hanmi to find new partner or open more options to commercialize efpeglenatide

Hanmi Pharmaceutical’s glucagon-like peptide-1 (GLP-1) agonist ‘efpeglenatide,’ initially licensed out to a global pharmaceutical company Sanofi in 2015, was ultimately returned to the South Korean company.

 

Four months after when the global company indicated its intention to return the rights on the drug May, Sanofi has decided to suspend clinical studies on the antidiabetic treatment and officially informed each clinical institutes.

 

Hanmi Pharmaceutical plans to take over all five Phase III clinical trials Sanofi was conducting, and look for new opportunities to commercialize efpeglenatide.

 

Over the past three years, three global Phase III clinical trials on efpeglenatide have recruited 5,391 participants, and collected a vast amount of data.

 

Various options are in discussion, such as finding a new commercialization partner in the antidiabetic treatment field, exploring new indications treating other metabolic diseases, and developing a combination therapy with the Korean company’s new drug pipeline.

 

◆Sanofi says “R&D strategy has changed,” and returns the rights over efpeglenatide after five years Apparently, the sign of the contract termination was looming from last year.

 

CEO Paul Hudson at Sanofi, held an investors event to talk about R&D strategies in late last year.

 

He declared the company "would halt researches in the diabetes and cardiovascular programs." His plan is to focus R&D investment in four areas, including oncology, blood disorders, rare disease, and neurology diseases.

 

Even at the time, Sanofi had unchanged commitment to continue developing the long-lasting GLP-1 agonist efpeglenatide.

 

The company was determined to complete the five Phase III clinical trials on efpeglenatide, but wanted find another commercialization partner to take charge of global sales and marketing activities after receiving the approval.

 

CEO Paul Hudson affirmed, “It was the best decision for the successfully launch of efpeglenatide while maximizing the productivity of our research engine.

 

It was irrelevant to efficacy and safety of the substance, and it would make no changes on license-in agreement with Hanmi Pharmaceutical." However, Sanofi overturned its initial position in just five months, and informed Hanmi Pharmaceutical of its intention to return the rights over efpeglenatide.

 

The two companies concluded the efpeglenatide returning procedure on Sept.

 

8 (local time) after a 120-day negotiation period as stated on the contract terms.

 

Hanmi Pharmaceutical would not take any legal actions like litigation for damage compensation the company has previously claimed.

 

Sanofi is expected to hand over all data collected from the on-going Phase III clinical trials to Hanmi Pharmaceutical, and step away from the entire development process.

 

Hanmi Pharmaceutical has also agreed to take over the one Phase III clinical trial to be completed in October.

 

Including the compensation and research cost coverage, the conditions for breaching the contract were undisclosed.

 

◆Market competition intensified with oral GLP-1 agonist Rybelsus The pharmaceutical industry pin points the cause of Sanofi giving up on developing efpeglenatide lies on the pipeline growing unattractive for the market.

 

The global GLP-1 agonist market is expanding rapidly.

 

Nevertheless, the industry sees that the latecomers would struggle to enter the market as multinational pharmaceutical companies like Novo Nordisk and Eli Lilly are firmly dominating the market.

 

(From left) Product image of Victoza, Ozempic, Rybelsus and Trulicity

Eli Lilly's once-weekly subcutaneous injection Trulicity (dulaglutide) owns majority of the share in the single therapy market.

 

In addition, Novo Nordisk is expanding its market presence as it added newly launched the world's first oral GLP-1 agonist Rybelsus (semaglutide) to its existing line up of once-daily subcutaneous injection 'Victoza (liraglutide)' and once-weekly injection 'Ozempic (semaglutide).'.

 

Lily's Trulicity generated global sales of USD 4.23 billion (approximately 4.91 trillion won), surging by 29 percent compared to the previous year.

 

The drug is expected to reach its new record in yearly sales as it made 2.50 billion dollars in the first half of this year.

 

Novo Nordisk's three GLP-1 agonists have earned overall DKK 33.22 billion (approximately 6.26 trillion won).

 

The Danish company’s first GLP-1 Victoza had a sales dip of 21.93 billion kroner, but the company had even more significant growth with the recently launched Ozempic sales increasing up to 11.24 billion kroner, and newly released Rybelsus making 50 million kroner.

 

In the first six months of the year, the Ozempic sales grew up to 9.60 billion kroner, and surpassed Victoza sales reaching 9.23 billion kroner.

 

Rybelsus marked six-month sales of 584 million kroner immediately after its release.

 

The three drugs’ sales in total reached 19.4 billion kroner (approximately 3.65 trillion won) in the first half of the year.

 

A GLP-1 agonist efpeglenatide has extended the administration term to once-weekly by incorporating Hanmi Pharmaceutical’s key platform technology, ‘Lapscovery’.

 

However, the industry experts analyze the investigational drug’s competitiveness as a follow-on drug is faltering when Trulicity and Ozempic dominate the once-weekly injection market and even an oral option Rybelsus emerges.

 

◆Hanmi with 6,000 participants’ data, committed to rekindle efpeglenatide’s potential The industry experts address Sanofi’s three-year worth of abundant clinical data as an engine to bring efpeglenatide back to life.

 

Sanofi has been operating five Phase III clinical trials since it signed the deal over efpeglenatide from Hanmi Pharmaceutical in 2015.

 

Two years into the deal, a Phase III AMPLITUDE-M study that compared efpeglenatide against placebo on the blood glucose level reduction effect was initiated from late 2017, and four Phase III clinical studies have started as of last year.

 

Following are the four Phase III trials; AMPLITUDE-D study compares efpeglenatide against Trulicity plus metformin combination therapy; AMPLITUDE-O study evaluates efpeglenatide’s effects on the cardiovascular system in type 2 diabetes patients; AMPLITUDE-L study administers efpeglenatide and other existing insuling treatment to type 2 diabetes patients; and AMPLITUDE-S additionally administers efpeglenatide to type 2 diabetes patients, who cannot control blood sugar level even after using metformin alone or metformin and sulfonylurea combination.

 

AMPLITUDE-M, AMPLITUDE-D and AMPLITUDE-O studies have completed subject registration.

 

Total 5,391 participants registered for the three studies.

 

Considering the number of participants registered for the remaining two studies, the number would sum up to around 6,000.

 

Hanmi Pharmaceutical plans to conduct and complete the AMPLITUDE-M study scheduled to end in October.

 

AMPLITUDE-M study is the first Phase III clinical study initiated by Sanofi after it licensed in efpeglenatide.

 

Companied called for participants from 56 research institutes in four countries including the U.S., Germany, Poland, and the U.K.

 

from December 2017, and compiled the roster with 406 participants by early September last year.

 

The endpoint of the study is to evaluate the change of goal is to evaluate the rate of change in hemoglobin A1c at week 30 of the treatment.

 

The entire study is scheduled to conclude by next month after the participants’ visits and data collection.

 

Based on the efpeglenatide data collected so far, Hanmi Pharmaceutical is determined to turn the crisis around with a plan to seek a new commercialization partner and also by opening options to explore new indications and research about combined treatment effect with other Lapscovery-based pipelines.