[Edaily Reporter KIM SAE-MI ] U.S.-based Viking Therapeutics has proposed the possibility of a once-monthly weight-loss drug without the need for a separate long-acting formulation technology. From the perspective of domestic developers of long-acting microparticle formulations, the fact that alternatives capable of achieving “once-monthly dosing” have increased is expected to pose a challenge.

Viking Overcomes ‘Side Effect Concerns’… Opens the Door to Not Just Weight Loss but Weight Maintenance

On the 22nd (local time), Viking Therapeutics released top-line results from a Phase 1 clinical trial of “VK2735,” a dual-action agent targeting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), for obesity maintenance therapy.

Buoyed by the confirmation of the feasibility of monthly and biweekly dosing, Viking’s stock price closed at $40.85 (approximately 55,300 won) on the day, up 35.67% ($10.74, or approximately 14,540 won) from the previous trading day. During the trading session, the stock soared as high as $41.73 (approximately 56,490 won), bringing its market capitalization to $4.77 billion (approximately 6.48 trillion won).

These results are also significant in that they have partially restored market confidence, which had been shaken last year by the results of the Phase 2 “VENTURE-Oral” clinical trial for the oral form of VK2735. At that time, while the oral formulation demonstrated a weight loss of up to 12.2% over 13 weeks, concerns about tolerability arose as the dropout rate due to adverse events was 20% in the VK2735 group and 13% in the placebo group. On the day of the announcement, Viking’s stock price plummeted by 42%. This time, however, gastrointestinal adverse reactions in the subcutaneous maintenance therapy group were found to be comparable to those in the placebo group, significantly alleviating previous concerns.

This clinical trial involved approximately 180 obese adults. Participants received either VK2735 or a placebo once weekly for 21 weeks; the VK2735 group started at 1.25 mg and increased the dose every two weeks, eventually reaching 15–22.5 mg. They then transitioned to once-weekly, every other week, once-monthly, or placebo administration for the subsequent 12 weeks. The VK2735 group lost an average of 16–19% of their body weight over the 21-week period.

Patients who extended their dosing interval to once a month maintained an average of 85%—and up to 90%—of their initial weight loss for three months. The maintenance rate in the biweekly dosing group averaged 90%, with a maximum of 97%. In contrast, patients who switched to a placebo maintained only 61% of their weight loss. Brian Ryan, CEO of Viking, commented, “This demonstrates the potential of a new approach that transitions from inducing weight loss through incretin-based therapy to maintenance therapy.”

The potential for market expansion is also drawing attention. This clinical trial involved patients who had been receiving VK2735 once weekly and were switched to every-other-week or once-monthly regimens of the same drug. This opens the door to future development of a “switch therapy” in which patients who have reached their target weight with other treatments switch to VK2735 once-monthly maintenance therapy. Although the efficacy and safety of switching from other GLP-1 receptor agonists—such as Wegovy and Mounjaro—to VK2735 have not yet been directly verified, analysts believe this potential for market expansion is what drove the sharp rise in the company’s stock price.

More Options for “Once-Monthly” Formulations… A Burden for the Domestic Microparticle Industry

These results are not entirely welcome news

for the domestic microparticle

-based long-acting formulation

industry

. In South Korea, Peptron, Inc.(087010)is developing long-acting injectables using its “SmartDepo” platform, #G2GBIO, Inc. is developing “InnoLAMP,” and Inventage Lab Inc.(389470)is developing “IVL-DrugFluidic.” These platforms share the common feature of encapsulating drugs in biodegradable polymer microparticles to enable gradual release over a period ranging from several weeks to several months.

The key value of these platforms was recognized as the ability to reduce the frequency of injections—which are currently administered daily or weekly—to once a month or more. However, Viking presented a case study showing that monthly maintenance therapy could be achieved simply by adjusting the dosing interval of long-acting new drugs. This suggests that, at least for maintenance therapy following weight loss, the number of doses required by patients can be significantly reduced without the need to incorporate external long-acting technologies.

Global pharmaceutical companies now have a wider range of options. In addition to converting existing weekly drugs into microparticle formulations, they can develop candidate compounds with long half-lives from the outset or adopt a strategy of administering the drug weekly during the weight-loss phase and switching to biweekly or monthly dosing during the maintenance phase. Another alternative is to lose weight with injectable medications and then maintain the weight with oral medications. Viking is also developing both subcutaneous and oral formulations using the same active ingredient, VK2735.

This could put pressure on the negotiating power not only of Peptron, Inc. but also of other Korean companies with long-acting platforms, such as G2GBIO, Inc. and Inventage Lab Inc. From the perspective of global big pharma, if it is possible to extend the half-life of a candidate drug or adjust the dosing interval without introducing separate microparticle technology, the need to adopt an external platform—and the willingness to pay for it—may decrease. In other words, the possibility of a simple once-monthly dosing schedule is no longer sufficient to demonstrate a platform’s competitive edge.

The fact that microparticle-based injectables are difficult to develop and manufacture could also be a stumbling block. The drug must be evenly encapsulated within a biodegradable polymer and designed so that it is released steadily over a specified period without being released all at once immediately after administration. Even during mass production, particle size, drug content, and release rate must be maintained uniformly, placing a heavy burden on sterilization and quality control.

Consequently, there are concerns that if similar effects can be achieved simply by extending the dosing interval of existing subcutaneous injections, global pharmaceutical companies are likely to prioritize methods that are relatively simpler to develop and produce.

“Different from New Drugs and Business Models… Microspheres Utilize ‘Proven Drugs’”

Counterarguments have also been raised, stating that it is difficult to conclude that Viking’s achievements have eliminated the need for domestic microsphere-based long-acting technology. This is because, although both approaches aim for once-monthly dosing, their technological starting points and business models differ.

Half-life extension technology involves altering the structure of the active pharmaceutical ingredient (API) or the characteristics of the drug itself to increase the time it remains in the body. In contrast, microparticle technology is a formulation technique that encapsulates an existing API within a biodegradable polymer and controls the gradual release of the drug as the polymer breaks down. It focuses on adjusting the release rate and dosing interval of an existing drug rather than redesigning the drug itself.

For long-acting new drugs like Viking, developers must first create a new candidate compound and then demonstrate its safety and efficacy through preclinical studies and Phase 1–3 clinical trials. Microparticle formulations, however, can utilize APIs whose safety and efficacy have already been confirmed in clinical trials, offering the potential to reduce development time and costs. Another strength is that they can be used as a means of drug lifecycle management (LCM) to enhance the convenience of administration and extend the product life of proven blockbuster drugs.

There are also technical differentiators that domestic companies can highlight. Peptron, Inc. is conducting joint research to apply its long-acting “SmartDepo” platform to multiple peptide drugs owned by Eli Lilly. G2GBIO, Inc. highlights the strength of its InnoLamp platform, which enables mass production while maintaining consistent microparticle size and drug release. Inventage Lab Inc. is focusing on enhancing particle uniformity and production process reproducibility by utilizing microfluidic-based manufacturing technology.

A representative from the domestic long-acting technology industry emphasized, “Microparticle technology can be applied not only to new drug development—which involves discovering new APIs—but also to business models that extend blockbuster drugs already validated in the market into long-acting products,” adding, “It offers differentiated business value as a platform technology that can be utilized in such LCM strategies.”