There is a pharmaceutical product that sells more than the annual sales of global fast-food giant McDonald's and global payment brand Mastercard. It is the immuno-oncology drug 'Keytruda.' Last year, Keytruda recorded sales of approximately $29.5 billion (about KRW 41 trillion). This accounts for about half of the total sales of $64.2 billion by Merck (MSD), the developer of Keytruda.

However, Keytruda's U.S. patent will expire in 2028. To defend the patent, MSD has changed Keytruda from an intravenous (IV) formulation to a subcutaneous (SC) formulation. This led to the meeting between MSD, one of the world's top three global pharmaceutical companies, and Alteogen, a bio company based in Daejeon, South Korea.

Recently, the SC formulation 'Keytruda Qurex,' developed by MSD and Alteogen, received sales approval from the U.S. Food and Drug Administration (FDA). An interview was conducted with Tae-yeon Jeon, Vice President of Alteogen, to discuss the changes in Alteogen and future plans following the approval.


It feels like just the beginning. Signing a technology transfer agreement does not always lead to commercialization. It seems that the strengths of our technology aligned well with MSD's business direction. Now that Qurex sales are starting, it is necessary to carefully monitor whether there are any issues and if it suits patients well. While there is a sense of relief from receiving approval, there is also a sense of tension.




Hyaluronidase is an enzyme that breaks down 'hyaluronic acid,' which plays a role in maintaining skin structure. Hyaluronic acid in the subcutaneous layer binds cells tightly, hindering the delivery of drugs to blood vessels. This is especially challenging for relatively large biopharmaceuticals like antibodies. By breaking down hyaluronic acid, high-dose biopharmaceuticals can also be delivered to blood vessels, meaning they can be administered in an SC formulation.

There are various types of hyaluronidase, and ALT-B4 is a newly created substance by recombining another hyaluronidase with 'PH20' found in human sperm. Using protein recombination technology, about 300 variants were created, and among them, ALT-B4 was the most stable and had the highest yield.

The stability of a substance is very important for commercialization. If the SC substance, which plays the role of 'penetrating' subcutaneous fat, easily breaks down, the dosage of the administered drug increases. In cases where the SC substance is unstable, the dosage may increase by 4 to 5 times. In the case of Qurex, the dosage is about twice that of the IV method of Keytruda, indicating its superior safety.


Receiving IV formulations is quite burdensome for patients. They have to receive injections for several hours, and some cancer patients need multiple injections. Even with just two injections, half a day can pass.

In the U.S., there are 'infusion centers' where patients go to receive IV formulations, in addition to general hospitals. It is not easy to make appointments at hospitals or centers. Waiting times are always long, and if appointments are not made correctly, it can be difficult to receive injections on time.

The SC formulation can be administered in 1 to 2 minutes, significantly reducing the time for both patients and medical staff, providing clear competitiveness. Even if Keytruda biosimilars are released in 2028, patients who have switched to the SC formulation before then will find it difficult to return to the IV formulation. MSD's strategy is to maximize the conversion rate from IV to SC before the patent expires.




When signing the royalty agreement with MSD, it was agreed that the milestone amounting to KRW 1.4 trillion would also be received in the form of royalties. Once the total amount received as royalties reaches KRW 1.4 trillion, it will be considered that all milestones have been received, and thereafter, sales based on actual royalties will occur.

Internally, it is expected that the milestone can be achieved in about 3 to 4 years. Around November, there is a high possibility that Qurex will also be approved in Europe. MSD internally expects that 40% of all patients will switch to the SC formulation by 2027. It is expected that this goal will be achieved without major issues, and if this ratio is maintained, significant royalties are anticipated.


There are several, although they cannot be disclosed (laughs). Discussions are ongoing with pharmaceutical companies that rank in the top 10 in global sales. Based on current confirmations, ALT-B4 can be applied to various types of drugs, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADC), and ribonucleic acid (RNA). This has broadened the range of pharmaceutical companies and drugs that can be discussed.

※Globally, only Alteogen and Halozyme have secured SC platform technology. In November last year, MSD filed a post-grant review (PGR) against Halozyme's SC platform technology 'Enhanze,' claiming that its patent scope is too broad. In April this year, Halozyme filed a lawsuit against MSD, claiming that Qurex infringed on Enhanze's patent.

Of the 14 PGRs filed by MSD, 5 have currently been initiated. (Typically, the U.S. Patent Trial and Appeal Board initiates PGRs when it determines there is a high possibility of patent invalidation.) In the U.S., there is a system called 'Discretionary Denial,' where the Director of the Patent Office can refuse to initiate a PGR. Halozyme requested the use of this system to deny MSD's PGR initiation, but all requests were dismissed.

There is such a possibility, but it is not considered high. For the court to issue a preliminary injunction, Halozyme must prove that it has suffered irreparable harm due to the sales of Qurex. However, this process is not easy. Halozyme has not yet commercialized any products using Enhanze. We have also conducted extensive analysis of the Enhanze patent, and since ALT-B4 is a separate substance from Enhanze, there is little concern about the patent.

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