An Industry Update: the Latest Developments in Therapeutic Delivery Covering February 2019

Abstract

The present industry update covers the period 1–28 February 2019, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. Reports on new financing (Ocular Therapeutix™ Inc.; MA, USA) and licensing (Moberg Pharma; Bromma, Sweden) transactions as well as codevelopment agreements combining complimentary expertise (Biocorp; Issoire, France and AgaMatrix; Dillingen, Germany) remain strong. Also, the introduction of connected drug-delivery devices continues such as for insulin of the these two companies and the insulin pump by Tandem Diabetes Care (CA, USA) triggering the US FDA to generate new special controls regulatory frameworks for these novel product combinations. But also, the creative use of biological materials like the CARGOCYTE™ of Cytonus Therapeutics Inc. (CA, USA) or freeze-dried insulin functioning as its own injector (Novo Nordisk; Bagsværd, Denmark) demonstrate a plethora of combination products just entering the development pipeline.

Keywords:

• connected devices
• controlled release
• gene delivery
• oral insulin

Business development

Reports

A report of February 2019 estimates the $14.6 billion retinal biologics market to grow 10.7% in 2019, as per a new Food Marketing Institute study [1]. Higher specificity of retinal biologics, compared with other traditional therapies, has enhanced research efforts in the retinal drug delivery field. Demographics, rising burden of diseases, the diabetes epidemic have increased efforts in finding cures for unmet medical needs. To develop long-acting therapeutics to reduce disease burden sets the stage for retinal biologics market.

Grand View Research Inc. (CA, USA) published a report on the global controlled release drug delivery market size. It forecasts to reach $90.18 billion by 2025, experiencing a compound average growth rate of 14.0% in that time frame [2]. The needs for geriatric and pediatric controlled release delivery techniques and alternative therapies is raising and provides new market opportunities of which oral controlled release systems have the largest market share in 2017 due to increased usage, ease of use, convenience and patient comfort. Targeted drug delivery is progressing the fastest while osmotic delivery by activation modulation might see the highest compound average growth rate as of its independence by factors, such as pH, food consumption and gastrointestinal motility.

On 4 February, Research and Markets published their report on Drug Delivery in central nervous system (CNS) diseases with the delivery method of a drug in this indication having a substantial impact on the commercial potential [3]. Considering the issues associated with delivering drugs to the CNS, direct administration into the CNS or systematic (e.g., by intravenous injection) for targeted action are preferred options. A major obstacle is the blood–brain barrier (BBB), but various control points for penetration such as carrier or transport systems, enzymes and receptors are known today. Various options have been explored to penetrate the BBB for drug delivery: osmotic and chemical opening of the barrier, use of transport and carrier systems, strategies to bypass the BBB as well as the conjugation of therapeutic molecules to liposomes and nanoparticles. Neurological active biologics, cell, gene, RNAi and antisense therapeutics are promising new treatment options innovative delivery methods will be needed.

Financing

Ocular Therapeutix

Ocular Therapeutix™, Inc. (MA, USA) addresses the formulation, development and commercialization of innovative therapies for diseases and conditions of the eye. On 21 February, the company announced that it has entered into an agreement with an investor to raise $37.5 million expected to be closed 1 March, 2019 and mature 2026 [4]. The expected proceeds from the offering are intended to fund the launch of DEXTENZA^®, which is approved for the treatment of pain following eye surgery and is a corticosteroid intracanalicular insert, designed to deliver up to 30 days of dexamethasone to the eye surface. After treatment, DEXTENZA is resorbed not requiring any removal procedure. Just a day earlier the company announced first-in-human multicenter, open-label study clinical trial of its OTX-TKI (tyrosine kinase inhibitor implant) Phase I, to treat of wet age-related macular degeneration. OTX-TKI is a bioresorbable hydrogel formulated with TKI particles in an injectable fiber that can be delivered through a small-gauge, sterile injection needle to the back of the eye. OTX-TKI is delivering the drug to the target tissues for a period of up to 9 months, thereby potentially extending the dosing interval. Preclinical data have demonstrated the ability to deliver TKI to the posterior segment of the eye with sustained pharmacokinetic and pharmacodynamic effect for the treatment of VEGF-induced retinal leakage for a duration of up to 12 months [5].

Sosei Heptares

Sosei Group Corporation (Tokyo, Japan) announced 4 February, to have entered into a €40 financing agreement with Medicxi (London, UK), a venture fund and will form two independent companies, Orexia Limited (Orexia; London, UK) and Inexia Limited (‘Inexia’; London, UK). They will pursue the development of novel therapies based on positive modulators of the G protein-coupled receptors Orexin OX1 and OX2 for neurological diseases, as a key regulator of behavioral arousal, wakefulness and sleep. Orexia will focus on the development of oral therapies, while Inexia will focus on the development of candidates for intranasal delivery using the Optinose Exhalation Delivery System. Specific target indications will be determined as the programs advance, and will include narcolepsy, a rare sleep disorder [6].

Licensing

Moberg Pharma

On 11 February, Moberg Pharma (Stockholm, Sweden) announced it had entered a licensing agreement with Bayer Consumer Health (Leverkusen, Germany) to grant rights to its onychomycosis-based MOB-015 patented proprietary formulation of terbinafine from its leading OTC product Kerasal Nail^®/Emtrix^® [7]. Upon successful completion of clinical development by Moberg Pharma Bayer will be commercializing MOB-015 in Europe. for up to €50 million milestone payments, mainly contingent on sales, development and regulatory targets. Approximately 10% of the general population suffer from onychomycosis, mostly untreated. MOB-015 is an internally developed topical formulation of terbinafine. Oral terbinafine is standard of care for the treatment of onychomycosis but has safety issues. In the ongoing Phase III study's primary endpoint is the complete cure of their target nail. Results from the North American clinical study are expected in the fourth quarter of 2019, followed by results in Europe in 2020.

Development & manufacturing agreements

Ompi & SiO₂ medical products

Stevanato Group (Padua, Italy) through Ompi, its specialist in glass primary packaging for the pharmaceutical industry, and SiO₂ Medical Products Inc. (SMP; AL, USA) jointly announced on 6 February a collaboration agreement. The agreement will provide pharmaceutical and biologics manufactures, contract filling organizations and research laboratories to receive SMP's proprietary primary containers in the EZ-fill^® form factor as trays, nest and tubs. This new and patented coating system provides the durability and consistency of plastics with the oxygen barrier properties, ultra-low extractables and pH stability of silica glass [8].

Biocorp

BIOCORP (Paris, France) focusing on the development and manufacturing of medical devices and smart drug delivery systems, and AgaMatrix Inc. (Dillingen, Germany) a developer and manufacturer of novel solutions for blood glucose monitoring, announce today that they have reached an agreement for distribution in the US and European markets and codevelopment activities. The two companies operate to improve compliance for diabetic patients and decided to join their efforts for providing a unique solution on the marketplace. BIOCORP designs, develops and manufactures Mallya^®, the add-on fitting insulin pen injectors that captures key treatment information (selected dose, date and time of injection) and transmits it to a dedicated mobile app. AgaMatrix gets non-exclusive rights to distribute Mallya^® in the USA, the UK and the EU market in the diabetes field. BIOCORP and AgaMatrix have also other co-development projects to offer a breakthrough innovation combining AgaMatrix and BIOCORP expertise [9].

Regulatory news & approvals

Product approval

ARS Pharmaceuticals

ARS Pharmaceuticals Inc. (CA, USA) a pharmaceutical company addressing at-risk patients of severe allergic reactions leading up to anaphylatic shock, announced on 19 February that the US FDA has granted Fast Track Designation for ARS-1. This is an investigational intranasal epinephrine spray providing a more patient friendly and more treatment option for severe allergic reactions to food, medications and insect bites. The drug is an aqueous formulation of epinephrine combined with Intravail^® to enhance nasal absorption. It has comparable pharmacokinetics to intramuscular injections of epinephrine with a low and safe intranasal dose, thereby providing easy delivery of epinephrine in emergencies compared to currently available auto-injectors [10].

Xellia Pharmaceuticals

Xellia Pharmaceuticals (Copenhagen, Denmark) a global leader in the manufacturing of specialty anti-infective treatments, announced on February it has received US FDA approval for Premixed Vancomycin Injection in a ready-to-use bag. This approval follows Qualified Infectious Disease Product designation from the FDA in February 2018 [11].

Tandem Diabetes Care

Tandem Diabetes Care Inc. (CA, USA) working on insulin delivery, published on 14 February that its t:slim X2™ insulin pump is the first to receive the new device category designation Alternate Controller Enabled Infusion Pumps (ACE pumps) by the FDA. The regulators are establishing criteria, special controls, to describe accuracy, reliability, cybersecurity and clinical relevance requirements of these pumps and what study data are needed for approval. The t:slim X2 pump has shown to reliably and securely communicate with connected devices, for example, automated insulin dosing [12].

Clinical trials

Foresee Pharmaceuticals

Foresee Pharmaceuticals Co. Ltd. (Taipei, Taiwan) announced on 21 February the open-label, single-arm study trial results for its FP-001 LMIS (Leuprolide Mesylate Injectable Suspension) in patients with prostate carcinoma. 97.9% of the study subjects achieving primary efficiency end point, the percentage of subjects with suppression of serum testosterone by day 28. The company is further pursuing regulatory submissions, and seeking partnerships like the recently announced with Accord Healthcare for the US market and Japan, Taiwan and mainland China [13].

Novus Therapeutics

Novus Therapeutics Inc. (CA, USA) is addressing patients with disorders of the ear, nose and throat (ENT) with two solutions for multiple ENT indications. OP0201is a combination drug product based on a surfactant, foam-based drug delivery technology for patients at risk for, or with, otitis media, middle ear inflammation with or without infection as a potentially first-in-class treatment option. On 11 February, it reported that it has dosed the first adult subjects in study C-001, a Phase I pharmacodynamics clinical trial. In addition to collecting additional safety information, this study aims to explore the potential effect of OP0201 on Eustachian tube function as subjects are exposed to changes in atmospheric pressure [14].

Publications

Gene delivery system based on dendrimer-loaded recombinant plasmid

On 15 February, Chen et al. published a study with a new, thrombus targeting nonviral gene delivery system [15]. It is based on PEGlyation polyamides dendrimers modified with RGDyC to package the plasmid DNA encoding the recombinant hirudine (rHV) gene and promises to significantly enhance transfection efficiency and antithrombotic effect. A recent trial demonstrated thrombus weight reduction in the RGDyC modified group and no significant difference in comparison to the heparin group, there was no. This gene delivery system may hold unique properties and promises in thrombus targeting therapy.

Cell-based technology by Cytonus

Cytonus Therapeutics Inc. (CA, USA) announced on 5 February that it has developed CARGOCYTES™ a first-of-its-kind, controllable, cell-based platform technology for delivery of biologics. CARGOCYTES are engineered allogenic cell lines that can carry a variety of payloads such as small molecule compounds, gene editing therapies, therapeutic RNAs and powerful biologics such as immune modulating cytokines, antibodies and oncolytic viruses. The company believes that CARGOCYTES have many structural and functional attributes making them a very versatile and capable cell-based drug delivery platform reducing adverse reactions, improve the efficiency of payload delivery, reduce the required dosing regimen, allow a cell therapy to be dosed multiple times using basic pharmacokinetic principles and mediate anticancer immunity against solid tumors and metastases. The company will first target pancreatic adenocarcinoma [16].

Insulin drug capsule

To date no oral form of insulin is available. Researchers from the Massachusetts Institute of Technology (MA, USA), Brigham and Women's Hospital (MA, USA) and Novo Nordisk (Bagsværd, Denmark) published an article about a pill containing a small needle made of insulin [17]. Once in the stomach it positions itself in contact with stomach tissue and injects the medicine. Preclinical tests successfully lowered blood sugar to levels similar to those seen with insulin injections as reported in the edition of Science published on 8 February. For this new capsule concept, the researchers developed a device that has a single microneedle with a tip made of freeze-dried insulin. The injection is controlled by a compressed spring that is restrained by a sugar disc. Water in the stomach can dissolve the disc and serve as the trigger to release the spring and inject the needle into the gastric wall [18]. Other entities such as Sanofi (Paris, France) working with Enteris BioPharma (NJ, USA) and Oramed (Jerusalem, Israel) have been working on other oral delivery concepts since a while with some now in clinical trials.

Financial & competing interests disclosure

Oliver Steinbach is an employee of Royal Philips Electronics North America Corporation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.