PD-1 inhibitors are a type of immunotherapy used to stimulate the body's own immune system to fight cancer. Historically, the treatment concept is relatively new, but is currently used to treat several different types of cancer. The treatment works by blocking the PD-1 receptor on T cells, which allows the immune system to recognize and attack cancer cells more effectively. In this class of drugs, keytruda (pembrolizumab) from Merck & Co the most prominent.
Since its launch in 2014, Keytruda has revolutionized the treatment of various tumor types and has become something of a global standard therapy. The drug has achieved enormous commercial success and has become the world's best-selling drug. In 2024 alone, Keytruda achieved global sales of 29,5 billion USD. Read more in BioStock's article ”The best-selling drugs in 2024". An example of another known PD-1 inhibitor is BMS Opdivo (nivolumab).
What are PD-1/VEGF inhibitors?
The pharmaceutical market is changing and the dominant position of PD-1 inhibitors will probably not last forever, but the question is what will challenge it. Much indicates that PD-1 inhibition will continue to play a major role in the future, when combined with another mechanism of action, namely inhibition of the protein VEGF. VEGF inhibitors work by blocking the formation of new blood vessels and thereby preventing tumor growth.
Among this type of medicine, Genentech Avastin (bevacizumab) best. The idea is that by combining these two mechanisms in a bispecific antibody, one can potentially provide a more powerful effect than when the therapies are used separately, in so-called monotherapies.
A Chinese challenger takes the lead
In September last year, results were released that show that they are somewhat on track. At that time, Chinese scientists presented Akeso promising study results for the PD-1/VEGF inhibitor ivonescimab, which in a phase III study (HARMONi-2) showed a significant improvement compared to Keytruda in the treatment of patients with non-small cell lung cancer.
The study showed that patients treated with ivonescimab had a median progression-free survival (PFS) of 11,1 months, compared with 5,8 months for those receiving Keytruda. Ivonescimab more than doubled the time before the disease got worse compared with Keytruda. Study results was published in the famous scientific journal The Lancet In the beginning of mars.
Ivonescimab is out-licensed to American Summit Therapeutics which is evaluating the candidate in several parallel phase III clinical studies in both the USA and China. In the USA, it has obtained Fast Track Designation by the FDA, which enables a faster and more cost-effective path to market.
Further research is required to address uncertainties
Despite the promising results from ivonescimab, there are still some uncertainties. In the HARMONi-2 study, ivonescimab was compared with Keytruda as monotherapy instead of the current standard of care where Keytruda is given in combination with chemotherapy.
Although ivonescimab has shown improved progression-free survival, overall survival data are still lacking. In conclusion, further study results are required before we can establish its role in the global treatment landscape.
Several drug candidates under development
The positive results for ivonescimab have, however, meant that the world has also opened its eyes to other PD-1/VEGF inhibitors under development. Merck in particular has reason to react to the growing threat from ivonescimab, not least because Keytruda's patent expires in 2028. As a strategic counter-move, the company has signed a licensing agreement worth up to USD 3,3 billion with Chinese LaNova Medicines current LM-299, a bispecific PD-1/VEGF antibody in Phase I clinical development.
BioNTech has also joined the game by acquiring China-based Biotheus and the Phase III candidate BNT327 in a deal worth up to 950 million USD.
Moreover, the development of PD-1/VEGF inhibitors is not only taking place in China. In London, Ottimo Pharma with the development of the PD1-VEGFR2 bispecific antibody JankistomachThe company was started last year and is led by David Epstein, former CEO of Seagen, which was acquired by Pfizer in a giant deal worth USD 43 billion. In December, Ottimo Pharma secured USD 140 million to take the preclinical candidate into clinical development.
The results solidify China on the pharmaceutical map
China's pole position in the development of PD-1/VEGF inhibitors has put a new spotlight on the country and strengthened its position in global pharmaceutical innovation. Previously, Chinese biotech companies have mainly focused on replicating existing drugs, but now we see a clear shift towards the development of more advanced treatments.
In addition, more large licensing agreements can be noted for Chinese-developed drugs, further cementing the country's growing importance in the industry. How the battle for next-generation cancer drugs ends remains to be seen, however, and BioStock will have reason to return to the issue.
