Investigation into the Feasibility of a 2 mL Needle-Free Injector

The current paradigm of injectable drug delivery has stagnated since the early 2000s. Despite recent innovations, like the launch in Europe of the first electromechanical reusable and connected auto-injector (UCB’s CIMZIA ava Connect® in early 2021), almost all new biologic drugs are launched with specific and undifferentiated self-injection options: a spring-based mechanical auto-injector (e.g., SHL’s Molly® and Ypsomed’s Ypsomate®) and a prefilled syringe, often with attached safety device, (e.g., Becton Dickinson’s UltraSafe Passive™). This now-common set of options only serves two classes of patients well.

The auto-injector appeals to patients who wish to avoid seeing a needle and can patiently wait for an injection to complete–albeit with sometimes ambiguous cues. The prefilled syringe works well for patients who are not needle phobic and prefer the control over the injection speed. Outside these two classes of patient, either device technology represents a compromise: patients may have to accept a medication with reluctance, need someone else to administer it for them, or seek non-injectable therapies that may require more frequent dosing, dietary restrictions, or a greater risk of serious adverse events (note the recent warnings and use restrictions placed on oral JAK inhibitors by FDA).¹ The lack of enthusiasm that arises from having only suboptimal device options may increase the risk of  poor adherence and poor persistence on therapy.

Additionally, the trend towards larger volume injections for patients makes these devices even less friendly to use and thus reduces their appeal.  This trend is a byproduct of the need for increased doses for either efficacy reasons or as a way to make dosing less frequent. Typical biologic concentrations are ≤200 mg/mL; with increased dose needs there becomes a trade-off between concentration which leads to higher drug volume or viscosity, which results in drug-delivery solutions that either take more time or force to inject. An example of this can be seen in the Instructions for Use for the AJOVY® autoinjector, which instructs patients that they will need to press and hold the injector against their skin “for about 30 seconds”. This is a product consisting of 1.5 mL of 150 mg/mL of fremanezumab. With the trend towards larger volume injections for patients–we note 2mL autoinjectors with similar use characteristics recently being approved for Dupixent® and Cosentyx® and more products studying 2mL devices clinically–it seems the burden on patients will not lessen anytime soon.

Makers of oral medications in certain classes seem aware of the opportunity created by a suboptimal patient experience, and are working to highlight it in their marketing. We note Pfizer’s branding of Xeljanz® as “Unjection™” as the most visible example of this.

Given this context, we see a significant opportunity to transform the patient experience with a reusable and connected needle-free injector. Having already demonstrated in our PRECISE II saline self-injection study that our needle-free drug delivery platform is preferred more than 8 to 1 (78% v. 9%) to a prefilled syringe amongst healthy volunteers  and injects with less self-reported pain, we sought to further explore our platform’s  potential with a 2 mL injection. In this study, dubbed PIONEER, we explored the feasibility of a 2 mL needle-free injection, a first using a handheld needle-free injection device. In the PIONEER study, we demonstrated similarity in patient-reported outcomes, including perceived pain and user preference between two 1mL needle-free injections and a single 2 mL needle-free injection. This demonstration of the feasibility of 2 mL needle-free injections and its comparability to two 1mL doses excites us to the possibilities for patients.

First, our technology allows for very rapid injection with a decrease in the perception of pain. Considering that a 2mL injection of biologic drug may require the patient to press an auto injector such as AJOVY®  device against their skin for 30 seconds, our platform’s capability to inject the same volume in 600 milliseconds, makes for a 50-times faster injection. There are potential advantages in user preference and reduced risk of user error (e.g. premature lifting of the device during long autoinjector delivery times, resulting in medication loss) with such a significantly faster injection time.

Next, the needle-free nature of our device may remove a significant barrier to acceptance and adoption of injectable therapies for users with needle fears, which is reportedly 25%² of the population. Many users, even if they lack needle anxiety, may be reluctant to bring an injectable medication into their home, fearing accidental use by or injury to children or others with which they reside.

Lastly, the environmental impact of needle-based injections is great and largely unquantified. A reusable system, like our needle-free injector, that produces less waste in total and eliminates biohazardous waste inherently would be a better choice for pharmaceutical companies looking to have a more sustainable impact. Altogether removing these disposable needle-based devices that are classified as biohazardous waste from the world will pay both direct monetary and other societal benefits.

As a fortunate secondary effect, the electromechanical nature of our system includes integrated connected health and digital capabilities, which could be used to drive patient adherence and persistence on therapy. Medication non-adherence is a significant drag on the positive and potentially life-changing benefits of all therapies, injectables included.

To learn more about our our needle-free platform and our promising 2mL clinical trial data, please view Bart Burgess’s presentation titled “Safety and Subject Preference of a 2.0 mL Needle-free Injection: Results of the PIONEER Trial” at the 2021 PDA Europe The Universe of Pre-filled Syringes & Injection Devices conference at 20:00h CET online.

[Note: All trademarks and company names are the property of their respective owners.]

¹ Center for Drug Evaluation and Research. “Serious Heart Events, Cancer, Blood Clots for Certain Jak Inhibitors.” U.S. Food and Drug Administration, FDA, 9 Sept. 2021.

² Wolicki, JoEllen, and Elaine Miller. “Vaccine Administration.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Aug. 2021.