Future Pharma Partner Models - Effective Drug Delivery

• That's Nice

Drug delivery plays a vital role in bringing a drug’s therapeutic value to patients. Facing intensive competition, drug makers are not only racing for new therapeutic entities, but also for novel drug delivery systems to fully realize the value of a known or new drug.

The primary function of drug delivery is to facilitate active pharmaceutical ingredients reaching the target site and exerting a desired efficacy and safety profile. Drug makers have been relying heavily on drug delivery systems (including excipients and formulations) to improve solubility of drug compounds and achieve better bioavailability. Poor solubility presents a major challenge for the pharmaceutical industry. Approximately 40% of marketed drugs and 80% of compounds in discovery and development suffer from low solubility and/ or low permeability.¹ Based on their water solubility and intestinal permeability, these compounds are categorized as Biopharmaceutical Classification System (BCS) II, III and IV compounds. In general, poor solubility leads to poor bioavailability, an indicator for therapeutic efficacy.

Pharmaceutical companies are actively seeking drug delivery technology to enhance bioavailability. According to the 2016 Nice Insight CDMO Outsourcing Survey, 53% of the buyer respondents acquire / plan to acquire bioavailability enhancing excipients from CDMOs / CMOs for BCS II–IV compounds, including peptides.² A variety of excipients can be used to improve solubility including surfactants, solvents, lipids (i.e., liposome), and polymers. Several technologies have been developed to improve oral bioavailability, such as solid amorphous dispersions, self-emulsification and self-microemulsification and hot-melt extrusion.³ Prodrugs also have shown to be an effective strategy to circumvent poor solubility and improve pharmacokinetics. In addition, novel drug delivery systems utilizing nanotechnologies, such as nanosizing techniques and nanocarriers, have been proven to be effective in enhancing bioavailability.⁴ One successful example is from NanoCrystal technology (Alkermes). Since 2000, NanoCrystal has been used in five FDA-approved products earning annual sales over $2 billion.³ The main technology used to boost bioavailability of biologics is pegylation — attaching polyethylene glycol chains to protein or peptide drugs can significantly improve the efficacy of biologics by increasing their stability in the serum.

Another drug delivery technology in high demand is controlled release formulation. In the Nice Insight 2016 CDMO Outsourcing Survey, 63% of the respondents expressed interest in acquiring or planning to acquire controlled release formulations.² Controlled release delivery system allows therapeutic agents to be released at a constant rate over an extended period. In comparison to traditional immediate release formulations, they are more effective and safer with lower dosing, less plasma variations and reduced side effects.⁵ Due to their simplified treatment regimen, a high level of patient adherence, can be expected.

The cost of not taking your medicine

In the U.S., medication nonadherence is a growing public health concern. Every year, 125,000 deaths and about 10% of hospitalizations are due to medication nonadherence, which costs healthcare $289 billion.⁶ In order to address this issue, new drug delivery systems that provide or enhance patient friendly features are needed. Improving the ease of administration is one way to improve patient adherence. Smart drug delivery systems (SDDSs) or stimulisensitive drug delivery systems are likely to play a more prominent role in patient treatment. Instead of releasing drugs on a fixed rate, SDDS releases drugs in response to a physical, chemical or biological signal in a programmable and predictable manner.⁵ The development of an artificial pancreas, in which insulin is automatically released in response to the blood glucose level has fully incorporated the concept of SDDS. The first artificial pancreas (Medtronic) for type I diabetes patients is expected to hit the market in spring 2017.⁷

Among the various drug delivery routes, oral dosage forms constitute the largest drug delivery category. With biologics being the fastest-growing segment in the pharmaceutical market, drug delivery technologies supporting biological administrations are gaining ground, including parenteral, transdermal, intranasal and pulmonary delivery. As demonstrated in the 2016 Nice Insight CDMO Outsourcing Survey, oral solid dose, namely in tablet or capsule form, represents two of the most popular dosage forms manufactured at the commercial scale (65%). Meanwhile, 41% of the respondents focus on specialty dosage forms manufacturing — transdermal and inhaler.²

Transdermal and pulmonary delivery are two hot areas in developing novel drug delivery technologies. These delivery systems provide fast onset of action, needle-free administration and versatility in delivering both small-molecule and macromolecule drugs. The transdermal/intradermal delivery is driven by microneedles or energy derived from battery, ultrasound or laser. The underlying technology for pulmonary delivery includes dry power inhalation (DPI) and pressurized metered dose inhalation (pMDI) systems.³ The approval of Zecuity (Teva), a transdermal, batterypowered patch for migraines in 2013 and Afrezza (MannKind), a rapid-acting inhaled insulin for diabetes in 2014, have infused excitement and energy into these fields.^{8, 9} Marketwise, injectable, pulmonary and transdermal delivery are the fastest-growing sectors in the drug delivery market and will grow at estimated double-digit rates from 2015 to 2020. The total market value for drug delivery was $1,048.1 billion in 2015 and is expected to reach $1,504.7 billion by 2020 at a CAGR of 7.5%.¹⁰

The drug delivery market is driven primarily by technology innovations and development of novel therapeutics. It is also driven by drug makers’ desire to extend patent lives and develop differentiated products. Innovative drug delivery has played an increasingly prominent role in helping drug developers gain a competitive edge. Big pharmaceutical companies are at the forefront to embrace novel drug delivery technologies. For example, GlaxoSmithKline is aimed to leverage innovative drug delivery technologies in 80% of its portfolio by 2020.¹¹

Novel drug delivery technologies can be acquired through in-house development, co-development, outsourcing and licensing. More often than not, though, companies are looking externally for drug delivery expertise. As a result, drug delivery has become the most active area within the pharmaceutical industry for partnerships.¹² Drug delivery systems for biologics (e.g., injectable, transdermal, pulmonary delivery) are popular areas for collaborations. There is an increasing demand for targeted drug delivery, especially in oncology and the central nervous system (i.e., cross bloodbrain barrier).¹³ The goal of targeted drug delivery is to transport drugs to the targeted site (i.e., intracellular structure) in a controlled manner, a step towards personalized medications.

References

1. “Special Feature – Excipients: Enhancing the New, Poorly Soluble APIs.” Drug Development & Delivery. 1 June 2015. Web.
2. The 2016 Nice Insight Contract Development and Manufacturing Survey.
3. Brooks, Kristen. “Advances in Drug Delivery.” Contract Pharma. 6 June 2011. Web
4. Beg, Sarwar, Suryakanta Swain, Md. Rizwan, Md. Irfanuddin, and D. Shobha Malini. “Bioavailability Enhancement Strategies: Basics, Formulation Approaches and Regulatory Considerations.” Current Drug Delivery 8.6 (2011): 691-702. Web.
5. Demir Sezer, Ali. “Recent Advances in Novel Drug Carrier Systems.” InTech Open Access Publisher. InTech. 31 Oct. 2012. Web.
6. Fung, Brian. “The $289 Billion Cost of Medication Noncompliance, and What to Do About It.” The Atlantic. Atlantic Media Company. 11 Sept. 2012. Web.
7. Miller, Annetta. “Personalized Medicine: Artificial Pancreas for Diabetics to Hit Market.” CNBC. 30 Mar. 2016. Web.
8. Petrochko, Cole. “NuPathe’s Patch for Migraine Wins FDA Approval.” Public Health & Policy. MedPage Today. 18 Jan. 2013. Web.
9. FDA Approves Afrezza to Treat Diabetes. U.S. Food and Drug Administration. 27 June 2014. Web.
10. Drug Delivery Technology Market by Route of Administration (Oral (Solid), Pulmonary (Nebulizer), Injectable (Device), Ocular (Liquid), Nasal (Drop), Topical (Solid), Implantable (Active), Transmucosal (Oral)), End User (Hospital, ASC, Home Care) – Forecast to 2020. Rep. Markets and Markets. Nov. 2015. Web.
11. Saxena, Varun. “GSK Exec Stresses Need to Move Away from ‘fragmented’ Approach to Drug Delivery.” Fierce Pharma. 21 Oct. 2014. Web.
12. Roumeliotis, Gregory. “Striking the Right Drug Delivery Partnership.” In-PharmaTechnologist. 31 July 2006. Web.
13. Choudhurie, Ruplekha. “Bioavailability Enhancement Strategies & Opportunities.” Drug Development & Delivery. 13 Mar. 2013. Web.