Some argue that the chemical design of small-molecule drugs has matured to a point where further innovation is challenging. However, over the past five years, small-molecule drugs have continued to dominate FDA approvals for new drugs. Between 2019 and 2023, small molecule drugs accounted for 65%, 62%, 56%, 46%, and 55% of these approvals, respectively. Thanks to their unique ability to penetrate cells and their convenience, small-molecule drugs have maintained a significant presence despite the rapid advancement of macromolecular drugs.
Advancements in technology, synthetic methodologies, and biopharmaceutical research have opened up new opportunities for innovative small-molecule drugs. For instance, the recently popular molecular glues and PROTAC technology directly address major challenges like drug resistance and undruggable targets. The evolution of small molecule drugs isn't limited to these revolutionary technologies that are still proving their worth. Gilead's long-acting HIV capsid inhibitor, lenacapavir, has already challenged the preconceived notion that small-molecule drugs are unsuitable for long-acting injectable formulations, showcasing the immense potential of long-acting injectable small-molecule drugs.
To develop more long-acting small molecule drugs, advanced drug delivery technologies and biodegradable polymer materials are essential for achieving sustained and controlled release, ensuring long-term efficacy for weeks or even months. Today, we will focus on the BEPO technology platform.
What is BEPO® technology?
The BEPO® technology enables the development of long-acting therapies, ensuring the controlled delivery of drugs at optimal therapeutic doses over several days, weeks, or months. This technology uses solutions of diblock copolymers (DB) and triblock copolymers (TB) to modulate drug release properties. These copolymers are composed of hydrophilic polyethylene glycol (PEG) and biodegradable hydrophobic polylactic acid (PLA). When exposed to water, the PEG-PLA copolymers form a drug reservoir as a residue. The active pharmaceutical ingredient (API) is encapsulated within the polymer matrix and is slowly released through diffusion and sustained polymer degradation. By adjusting the hydrophilicity of the copolymers, the composition and molecular weight of DB and TB, the ratio of PEG to PLA in the copolymers, or the proportions of API, polymer, and solvent, the hygroscopicity of the drug reservoir and the API release kinetics can be finely tuned.
Figure 1. BEPO Technology
On April 16, 2024, Medincell and AbbVie struck up a co-development and licensing pact to create up to six long-acting injectables across “multiple therapeutic areas and indications, Under the deal, Medincell is line to receive an upfront payment of $35 million, plus up to $1.9 billion in potential development and commercial milestones, as well as royalties on global sales.
Figure 2. Drugs with BEPO technology
On April 28, 2023, Teva and MedinCell announced FDA Approval of UZEDY™ (risperidone) extended-release injectable suspension, a long-acting subcutaneous atypical antipsychotic injection, for treating schizophrenia in adults. This is the first subcutaneous long-acting formulation based on BEPO® technology approved by the FDA, administered once every one to two months. Utilizing MedinCell's proprietary BEPO® technology, it ensures the controlled and stable release of risperidone without the need for oral supplements or loading doses. Therapeutic blood levels can be achieved within 6 to 24 hours after a single administration.
Figure 3. UZEDY™ (risperidone)
Notably, UZEDY® was approved based on data from two Phase 3 clinical trials that evaluated its efficacy in patients with schizophrenia. In one of these trials, UZEDY® reduced the risk of schizophrenia relapse by up to 80% compared to a placebo.
Conclusion
Extending the dosing interval can significantly improve patient compliance and offer substantial clinical value. MedinCell's BEPO technology allows for the controlled release of small molecule drugs following subcutaneous injection, enabling dosing intervals of once a month or even longer for some medications.
As a leading PEG derivative supplier, Biopharma PEG can provide PEG derivatives for your long-acting drug development. PEG derivatives with various functional groups are provided in both GMP and non-GMP grades, contact us to learn more.