Can Nordic companies extend the life of Keytruda?
Merck’s cancer drug Keytruda is one of the best-selling drugs in the world right now. But with the main patent expiring in 2028, the pharmaceutical giant has begun to review its strategy to maintain its top spot on the oncology market. BioStock has taken a closer look at the history of Keytruda, what lies ahead and what that means for biotech companies in the Nordic region.
Keytruda is one of the big success stories in the immuno-oncology world. With sales of 17.2 billion USD in 2021, the checkpoint inhibitor has a stable position in the list of the world’s best-selling drugs. Not counting the Covid-19 vaccines, Keytruda last year clinched spot number two on the list, just behind Abbvie’s Humira. With the current sales trend, Merck’s bestsellers look set to clinch first place in the near future.
But the road to success has been far from smooth; in fact, the project has been threatened with closure on several occasions.
Activating the soldiers of the immune system
Keytruda, or pembrolizumab, which is the generic name, is a checkpoint inhibitor that targets the PD-1 receptor on the immune system’s soldiers, the T-cells. The PD-1 receptor keeps the T-cells from attacking the body´s own tissue, and cancer cells have been found to take advantage of this receptor to hide from the immune system. By blocking the PD-1 receptor, pembrolizumab exposes cancer to the immune soldiers, enabling them to go on the attack.
Stemming from a project aimed at autoimmune diseases
However, that was not the original idea for the treatment. Keytruda stems from a project at the American company Organon, which, at the time, was part of the Dutch conglomerate Akzo Nobel. The project was aimed at developing substances that, on the contrary, increased the reactivity of the PD-1 receptor to counter various autoimmune diseases. But drug development is rarely a straight path to success and that’s true even in this case.
When the programme ended up with American Merck in 2009, it had such a low priority that it was put on the list of projects to outlicense. However, positive clinical study results for a similar substance developed by competitor Bristol-Myers Squibb changed Merck’s priority drastically.
Approved in 2014
After taking the project through clinical studies, Keytruda was approved in 2014 for the treatment of metastatic melanoma. Since then, several cancer indications have been added to the list, and the rest, as they say, is history.
But even the best of fairy tales come to end. Merck is slowly moving towards patent expiration for its bestseller – the patents for Keytruda expire in 2028 in the US and 2030 in Europe. Now the focus lies increasingly on how the American pharmaceutical giant chooses to handle the competition expected from biosimilars once the time comes. One strategy is to continue to build on the product portfolio and a significant step on that journey was taken by Merck in 2021 when the company announced the acquisition of US Acceleron Pharma for 11.5 billion USD.
Trying to improve survival via combination therapies
However, the company is not only defending its position in the oncology market through acquisitions and diversification. Another way is to find new patentable combination therapies where Keytruda is used together with other drugs, strengthening the patent protection surrounding the product.
Clinically, the goal of the combinations is to strengthen the immune system’s ability to localise and attack cancer in various ways. Just as people are unique, cancers behave differently too. This depends in part on which cancer indication we are talking about, but also on the person that has been affected. In other words, not even Keytruda is effective in every case, and this is the treatment gap that people are trying to fill.
Several Nordic partners
Right now, several hundred clinical studies are underway with this precise goal, where Merck is often a clinical partner. Of these studies, a handful are run by Nordic listed biotech companies, such as Ultimovacs, Evaxion Biotech, BioInvent and Mendus.
In Ultimovacs’ case, the cancer vaccine candidate UV1 is being developed for the treatment of several cancer indications in combination with anti-PD1 checkpoint inhibitors. Among other things, UV1 is being investigated in combination with Keytruda in malignant melanoma, head-and-neck-cancer, and non-small cell lung cancer. Read the latest update from the company here.
Evaxion Biotech has developed an AI platform for the rapid and effective detection and development of immunotherapies, enabling a patient-specific treatment. In 2021, the company signed a clinical collaboration agreement with Merck regarding the phase IIb study with the drug candidate EVX-01 in patients with metastatic melanoma. Evaxion Biotech recently recruited the first patient to the study. Learn more.
Lund-based BioInvent develops antibodies designed to improve the efficacy of current checkpoint inhibitors and/or activate immunity to cancer in patients who no longer respond to treatment. BioInvent currently collaborates with Merck on three development projects: BI-1206, BI-1808 and BT-001. BI-1206 is the project that has come the furthest, where the candidate is evaluated in two separate clinical phase I/IIa studies. Learn more.
In Mendus’ case, candidate DCP-001 targets tumour recurrence. The cancer recurrence vaccine is being developed to reduce, delay, or even prevent recurrence of some of the most dangerous tumours, including acute myeloid leukaemia (AML), ovarian cancer, and more. Last spring, the company announced positive interim results from the phase II ADVANCE II study with DCP-001 for AML maintenance. Learn more.
Potential for big money
Whether any of the aforementioned projects will succeed is too early to say. What we can say, however, is that there is potential for big money for whomever is able to go all the way through the clinic with the respective candidates. On that journey, these companies have a strong partner in Merck, who is very motivated to extend the life of its bestseller as much as possible.