Akeso's Ivonescimab Adds Third Lung Cancer Indication in China

Chinese drugmaker Akeso has received approval to use ivonescimab in combination with chemotherapy for the treatment of advanced squamous non-small cell lung cancer. This marks the drug's third indication for lung cancer in China.

The National Medical Products Administration approved ivonescimab based on the HARMONi-6 study, which looked at how ivonescimab works compared to BeOne's PD-1 drug tislelizumab plus chemotherapy, Akeso said on Wednesday.

The approval expands ivonescimab into a first-line market where PD-1 medicines combined with chemotherapy are already widely used. Whether the drug can gain significant market share, however, will depend on its price, hospital access and eligibility for national reimbursement.

In the trial involving 532 patients in China, ivonescimab plus chemotherapy reduced the risk of death by 34 percent compared with tislelizumab plus chemotherapy. Median overall survival was 27.9 months in the ivonescimab group and 23.7 months in the control group.

The treatment also reduced the risk of disease progression or death by 40 percent. Patients receiving ivonescimab had a median of 11.1 months before their cancer worsened, while those receiving tislelizumab experienced a median of 6.9 months.

The 24-month survival rate was 64.7 percent in the ivonescimab group, versus 48.6 percent in the control group. The survival benefit was observed in patients with both positive and negative PD-L1 levels, a marker commonly used to assess whether a patient may respond to immunotherapy.

"This regimen has rewritten the gold standard of care and represents a landmark advance in the treatment of lung cancer," said Professor Lu Shun, the trial's principal investigator and director of the Oncology Department from Shanghai Chest Hospital.

That description reflects the investigators' and company's view. The trial sets ivonescimab apart because it was tested directly against an approved PD-1 treatment instead of just chemotherapy or a placebo, and it showed better results in slowing down the disease and increasing survival.

Ivonescimab is a bispecific antibody that blocks both PD-1 and VEGF. PD-1 drugs help the immune system recognize and attack cancer cells, while blocking VEGF is intended to restrict the blood supply that tumors use to grow.

Akeso's founder, chairwoman, president and CEO, Xia Yu, said the results had established "a new benchmark for clinical benefit."

The approval comes as China's PD-1 market faces intense competition. A number of domestic PD-1 drugs have secured approvals in recent years, while national reimbursement negotiations have pushed down prices and widened patient access.

Ivonescimab may be able to compete on its head-to-head clinical results rather than price alone. The newly approved regimen can also be used regardless of a patient's PD-L1 level, giving it access to a broader group of patients.

But the stronger trial results do not necessarily guarantee rapid commercial uptake. Lower-cost PD-1 therapies are already available, and doctors and hospitals will have to weigh ivonescimab's additional clinical benefit against its price and safety profile.

Severe treatment-related side effects occurred in about 69 percent of patients in the ivonescimab group, compared with 59 percent in the tislelizumab group. Severe bleeding was also more frequent among patients receiving ivonescimab. Rates of treatment discontinuation and treatment-related death were similar between the two groups.

Ivonescimab is also the subject of one of China's largest overseas drug-licensing agreements. Akeso licensed the drug to US-based Summit Therapeutics in 2022 in a deal worth up to US$5 billion, including US$500 million upfront.

Summit holds development and commercialization rights in major overseas markets, including the United States, Europe and Japan. Akeso retains the rights in China and some other Asian markets.

The latest approval adds to the clinical evidence supporting the drug, but the HARMONi-6 study was conducted entirely in China and used tislelizumab as the comparator. Its findings cannot by themselves establish ivonescimab as a new treatment standard outside the country, where Merck's Keytruda remains a widely used immunotherapy.

A separate international Phase III study, HARMONi-3, is comparing ivonescimab plus chemotherapy directly with Keytruda plus chemotherapy. Those results will be important in determining whether the benefits seen in Chinese patients can be reproduced internationally.