Needle-Free Rescue Therapies With Crossject's Patrick Alexandre And Dan Chiche

Just how quickly might the emergency treatment of an epileptic seizure or other sudden, chronic attack be enabled? With advances in needle-free autoinjectors, the promise of near immediacy is near. In this episode of In Combination, host Tom von Gunden combines perspectives from two different executive roles at emergency medicines company Crossject. CEO Patrick Alexandre and Chief Medical Officer Dan Chiche discuss common rescue scenarios, rapid self-administration of treatments, and collaborative development efforts across drug formulation and device engineering.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of In Combination. My name is Tom von Gunden, Chief Editor and Community Director at Drug Delivery Leader. For today's In Combination conversation, I am joined by two representatives from Crossject, a pharmaceutical company working on therapeutic advancements in the areas of rescue indications, starting with epileptic seizures. The folks who are joining me are CEO Patrick Alexandre and Chief Medical Officer Dan Chiche.

Welcome, Patrick. Welcome, Dan.

Patrick Alexandre, CEO, Crossject:

Thank you very much.

Dan Chiche, Chief Medical Officer, Crossject:

Thank you.

Let’s start with a quick career tracing from both of you.

I'll start with you, Patrick. Tell us a little bit about how you worked your way to where you're now the CEO of a company working in rescue therapy areas. [Then] Dan, I'll ask you to echo that in terms of how, as a medically focused person, you landed in the same arena.

Patrick, you want to give us a little bit of context of why Crossject and how you got here?

Alexandre: This is quite an odd trajectory for me. I am an electrical engineer, and I started to work in the steel industry. In 1997 I came to [a] drug delivery division inside a French pharmaceutical company to work on an electrical patch. We also worked on a way to self-administer — to ease administration of —a parenteral drug, which are normally the most efficient with the least side effects. But at the end of the day, only feasible by medical personnel, such as doctors and nurses. This is why we started to work on needle-free injections. When the company I was working at was sold to another, I had the opportunity to take all the rights of the project and to build or to create Crossject in 2001. This is why I'm CEO and founder of Crossject.

Thank you. Dan, how would you describe how you arrived where we are today?

Chiche: I am a physician by training, very much interested in disease indications and patient well-being. By training, I am an emergency physician. Many years ago, I decided to join the pharmaceutical industry, and I worked on multiple types of devices, but I essentially worked on the new product, new medication. At the end of the day, what is important is the added value for patients. When you come in with a new drug, you are adding value for the community and for the patient.

In this case, with the project as a device, the device is definitely added value for the patient. And for me, that's very important—— to work on something with innovation value. And [I am] very pleased to be back in my initial area of expertise, which is emergency medicine.

All right. Great. So, I'd like to talk about, or hear about, where we are in terms of the current state of options and opportunities for advancement in the area of rescue therapies.

So, starting with you, Patrick, on the business value aspect of that — positioning Crossject and the kinds of things you'd like to offer that address therapeutic areas and patient needs. Can you give us a little bit of, where do you think the current state is, given what has happened in terms of advancements thus far? And what is Crossject looking to do in terms of the breadth of what it can potentially provide in these areas of rescue therapies?

And then, Dan, I'm going to ask you about, from a medical perspective, what some of these advancements might address, from the [perspective of] benefits to patient health and needs.

So, Patrick, how does Crossject see itself in this arena?

Alexandre: And so, as I mentioned, we started to develop an epilepsy injection in order to allow administration of the drug by the patient. So, we worked hard on designing a product that is very easy to understand and very safe to use. And, at the end of the day, when we were looking at different indications, we saw that some indications — what we called the emergency situation — [must be treated] out of hospital.

So, you have a seizure, you call the rescue teams, and your team may be there some minutes later, and it can take half an hour or one hour before you get to the hospital. And for some of these indications, this time is critical. For example, epileptic seizures: in the US, you have more than 5,000 deaths [annually] due to epileptic seizures.

And, this is clearly a segment, an indication, where there is a need to reduce the risk of death by injecting, as soon as possible during a seizure, an emergency drug. This is the case for epilepsy. It's also the case for allergy shots. And there are some other indications where we decided to concentrate first because there are life-threatening situations.

[Let’s]  go back just a little bit: I don't know how far back it would be appropriate to go —  5, 10, 20 years — what has been the typical way that this was approached or addressed and with what effect? And what would you hope some of the work that you're doing would do to better those scenarios for folks?

Alexandre: A long time ago, the only possibility was to have the injection of the drug once you are at the hospital. So, this is the reason there are quite a lot of deaths in some situations for some indications, like anaphylactic shock, allergy shock. There are some products where the patient’s diagnosis has some risk of having a seizure, [so the patient] has an emergency dose everyday with him. This is an autoinjector with a needle; this is a syringe inside a pen.

So, there are some products that are well-known for that, but these products are quite difficult to use. And some studies show that more or less half of the population do not use them correctly. And this is why we are bringing solutions very easy to understand and to use in order to have the full dose at the right moment.

Yeah, okay. Thank you.

Dan, how about picking it up from there, from your perspective as a former practicing physician, particularly in the areas of emergency treatments. What do you have to say about what it was like and has been like, in the old days or the current days, and what you're hopeful for, having [since] joined Crossject, from having [had] those experiences?

Chiche: The first thing I have to say is that, hopefully, the business perspective and the medical perspective, at least in this case, are very much aligned, which is very important. That's number one.

Yeah so, epileptic seizures: The indication we are looking for is status epilepticus — some sort of prolonged seizure. And this is a very difficult situation because, yes, it could lead to death, but we also know — and it's very well documented — that the duration of seizure is directly linked to brain damage. So, the unmet medical need is clearly to control the seizure as soon as possible.

I would like to add, because we need to care about the patient but also about the caregiver, the people around the patients. I'm sure that you have seen many movies where you have people having seizures, starting with the famous Roman, Caesar [in the 2021 film Rome], where the people around him were doing very weird things like giving something to bite or whatever it is.

But the point that I would like to make is that, for the people around the ones who have a seizure, it's very difficult just to wait. And what is still done today is that the only thing that you could do is to call the emergency organization, 911 in the U.S., and essentially to wait. And this waiting period is the main issue and is essentially what we call the unmet medical need that we need to work on. And we'd be very pleased to explain why our product is really adding value to these unmet medical needs. But essentially, that's what the situation is.

Great. And as we look to the future of potential other therapeutic areas or indications for this kind of technology and these kinds of formulations, what's potentially on the horizon, outside of the area of epileptic seizures, that might be addressed?

Alexandre: The next indication we are working on today already is allergy in [the] case of anaphylactic shock. So, there are some products, some autoinjectors, with needles already on the market, but there is still unmet need due to the fact that there is a high risk of misuse of these devices. So, there are some other indications, in asthma and so on. But, clearly today, we are, as was mentioned by Dan, we have some groups that are working in order to sort the indications in terms of importance.

For example, we are also working on adrenal insufficiency. Some people may have some seizures after a stress or an episode. This is more or less a rare disease and very difficult to diagnose when they come to the hospital. And they have no solutions today that can be used by nonprofessionals. So, these are examples of indications we are already working on.

Is there any difference in the way the scenarios around those would differ in the way that the technology would need to be applied or used from a medical practitioner’s or drug deliverer’s perspective?

Chiche: Yeah, it's a good question. But at the end of the day, what is the value of the Zeneo® Crossject device? The value is that it is extremely simple. You cannot make a mistake when you use it. It has been tested on thousands of nonprofessionals. And you essentially, virtually, cannot make a mistake with the device. Very simple.

On top of that, you eliminate all sorts of accidents. You can start with — one typical accident is one having an accident with the needle. There are no needles. So, the device by itself is extremely safe.

And on top of that, you cannot make any mistake with regards to dosage. Why do you need a professional? [In scenarios] when you have a vial and a syringe and the needle, [and] you need to do the calculation, milligram volume, and you extract something. Here [with the Crossject device], you cannot make any mistake. The dose is the dose that is in the device because it is ready for use, and it has to be used just once.

For example, the dose of midazolam is 10 mg. It’s nothing else but 10 mg. So, there is essentially no possibility of making a mistake, and that typically is the situation we are looking for. We are looking for a situation where the value of the drug is properly established. And that is the case for midazolam because, [on] both sides of the Atlantic, midazolam intramuscular is recommended as a first-line therapy for status epilepticus at the dose of 10 mg.

So, the product could not be challenged. It is well known, recommended worldwide, dose established, etc. The only thing that we add onto that is that we provide the device so that it can be injected much more rapidly without, potentially, the need for a professional. So that, instead of having to wait 10, 20 minutes for the professional to be on site, it could be done within minutes by someone around the patient with the risk of status epilepticus.

A question I hadn't thought to ask you, but since you mentioned dosage, Dan, I'll ask either one of you, or you can both weigh in. I hope this doesn't put either of you on the spot; I don't think that it will. When I think about this concept of In Combination, one of the combinations that we often encounter is the combination of formulators and device folks, and to what extent they communicate and collaborate to work on making the devices work with the formulations, and vice versa.

So, can you provide any insight into how those different roles interact and collaborate and communicate within Crossject to make sure that the devices and the formulations work well in concert with each other?

Alexandre: Yes. Of course. So, the first thing, as you could see [from] what Dan is saying, the first is to have the choice of the right indication, where we bring this service to the patient. And then from that, once a drug is chosen, to define the dose and what is specific to the project. Inside the company, we have people working on the formulation side and people working on the engineering side.

So, we built a project, [a] combined project, where we ask the formulation team — for example, our device is able to inject volumes from 0 to 0.7 mL. So, first is to have a formulation in this area. It could be either subcutaneous or intramuscular injections. From that, once we have the specification from the medical point, we then adapt the device, we tune the gas generator that pushes the drug through the skin so we can push slower or harder, depending on the depth.

So, in the same building, we have the teams for formulation and engineering. And [as this] project is also manufacturing, we take into account all the specifications of the needs for the manufacturing. This is why we have the master — the complete design and validation process from the drug to the complete product, including the device.

Chiche: And if I add [to] that, it's a very interesting point as well, because Patrick just mentioned that the volume for midazolam is 0.7 mL. This is very important because a very small volume is then allowing the injection within a fraction of a second. What we should mention is that the traditional 10 mg midazolam corresponds to a volume of 2 mL. So, something in the range of 4x the volume of what is in the Zeneo® device.

And so, I take this opportunity to mention that, even if you are the professional on site, with Zeneo®,  you just take the device, you take off the cap, you inject everything within a fraction of a second. Whereas [without this device] even if a professional is on site, [that person] has to take a vial, clean up to avoid any sort of contamination, then take a syringe and needle, take the volume, 2 mL. And then you have the syringe, the needle. And then you will be doing the injection.

But if you want to inject 2 mL, you cannot inject 2 mL within a second. You need to take something in the range of 20 [or] 30 seconds in order to inject properly these, let's say, large volumes. So, all together, even with a professional on site: on one side, you have an injection that, because of the volume and the device, could take place within seconds. And then [on] the other side, even with a professional, you need something that is in the range of three minutes.

Great. And just, I'll take it right up to a high level as we close. Is there any quick key to the future that either one of you would like to point to, whether it's the benefits in lives to patients or challenges that need to be addressed that you'd like to highlight before we close?

Alexandre: So, the needs, the specification, the expectation from the authorities for such a device is that, first, it's easy to understand and to use, and also reliable. So, the life of the patient is attached to the device, and it's designed and proven in order to have virtually no risk of failure, including the way it is used by the patient, but also in the manufacturing, in the quality testing, and so on.

This was very challenging to develop that. And this is why we think we have, beyond the three indications we mentioned, there are many other situations and projects. We work specifically on each of these indications. Each time we have a drug that can be formulated in less than 1 mL, it means that we have the possibility to put that in the device and adapt the device to inject the right dose, [to] the right tissue, [at] the right depth.

All right. Well, great. Well, Patrick and Dan, I'd like to thank you both for joining me on an episode of In Combination. I'd like to also thank our audience for joining, and we will see you next time.