From IV To Subcutaneous: Easing Administration, Advancing Efficacy

In this episode of In Combination, patients Todd Kennedy and Cathleen Bergin describe for videocast host Tom von Gunden the significant life and health transformations brought about when their treatment regimens shifted from IV to subcutaneous administration. Adding perspective on the technology enablers is Chief Medical Officer Charles Theuer from drug delivery systems provider Halozyme. 

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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 at Drug Delivery Leader, and your host for the episode.

Today, I'm pleased to be joined by an expert panel to talk about some of the changes in routes of administration for folks — from IV or infusion types of delivery to subcutaneous. And, especially, the benefits around patient convenience and access that that [change] allows.

I'm happy to be joined by a couple of folks who have some patient experience to share about that. And I'll start with one of those folks, and that's Todd Kennedy, who is a patient and research advocate based on some of his experiences.

Welcome, Todd.

Todd Kennedy, Patient and Research Advocate:

Thanks, Tom. Glad to be here.

Also joining me from the patient experience side is Cathleen Bergin. Cathleen is also, coincidentally, working within the biopharma industry. She is at argenx, and there she is Head of Field Clinical Educator Team for the U.S.

Welcome, Cathleen.

Cathleen Bergin, Head of Field Clinical Educator Team, US, argenx:

Thank you. Glad to be here.

Thank you, it's great to have you here.

And finally, I'm also joined by Charles Theuer, who is Chief Medical Officer at biotech company Halozyme, which focuses, in particular, on drug delivery systems.

Welcome, Charles.

Charles Theuer, Chief Medical Officer, Halozyme:

Morning, Tom. Great to be here.

Great to have you. So, thank you all for joining, and let's go ahead and dive in.

So, let's, all three of you in some fashion, take us back in your experiences to ‘back in the day’ versus today.

And I'm going to start with you, Todd. If you could share with us your initial diagnosis, the indications that you were being treated for. How did that go for as long as it went the way it was going, both for you and your caregivers and so forth? And then, we'll pause and later pick up what it's like for you today. But if you can go back and trace that story a little bit for us?

Kennedy: Yeah, thanks again, Tom. So, I was diagnosed in December of 2017, pretty much out of the blue, with a relatively rare but highly complex blood cancer called multiple myeloma. And the kind of bummer part about this is it's currently considered incurable. So, we're making great strides, not only in treatment options, but also on how you go through that patient experience. And so, hopefully it'll move from incurable to cured at some point, but it is a marathon, to say the least in its current state.

So, in February of 2018, I started what was a really leading-edge quadruplet therapy combination that has now become standard of care. But it was really kind of leading edge at the time. So, that four-drug combination included Darzalex (daratumumab), and at the time, that was an IV formulation. It also included subcutaneous Velcade, oral dexamethasone, and oral lenalidomide.

[We] followed that with transplant, or actually radiation then transplant, and then ongoing maintenance that I take to this day. In fact, I had a Darzalex shot on Friday, and I took my chemo this morning. So, it's an ongoing treatment plan.

But that has actually been very effective because, in November of 2018, my care team and I declared that I am in complete response. So, I'm in remission. It has been a deep, durable remission that has lasted all the way to this day, and hopefully for years to follow.

But those first two years — you wanted to trace it back to the beginning — because there was … the treatment has been very effective, ongoing, but the patient experience has really evolved. And in the first two years, it was a pretty grueling experience. The challenges were really linked to the delivery of kind of the anchor of that treatment, which was the Darzalex. As I mentioned, it was IV at the time.

And so, let me describe what those first two years looked like for, not just me, but also for my wife. We would wake up before sunrise and get in the car to drive an hour and a half to the treatment center in Los Angeles traffic, which was no fun. I'd get my labs at 8. I would be upstairs to see my doctor at about 9. And then I'd be up at the infusion center around 10.

I'd see the nurses. They would release the orders to the specialty pharmacy, they'd start the packaging, do the weight-based calculations on the dose and everything else. And while we were waiting for pharmacy to get the Darzalex and the premeds mixed and ready, those nurses would start trying to set the IV line.

And, you know, one nurse would come in, and she'd say, “Oh, okay, that looks great.” She'd say, “Which side do you prefer?” ’d say, “I don't care; you just pick whichever looks good to you.” And she'd say, “You know, okay, we'll start here, that's a juicy vein.” And I'd say, “Don't do that one because that one's going to roll. That's not going to be fun for me or you.”

And so, they'd try again, and typically, I'm not kidding, it would be two or three pokes. And I'd be grimacing, and they'd say, “Does that hurt?” And I'm like, “What do you think? You know, of course it hurts. You could see that it hurts.” They'd call in reinforcements. It was a pretty traumatic experience. It's not just, hey, pop an IV line, and it's no big deal. And I know a lot of patients struggle with just even setting that IV line.

So, after multiple attempts, they'd get the line established. The drugs would come in, and then the premeds would typically start around 11; the Darzalex would start around noon. At the beginning, back all the way in 2018, that was a 3-hour infusion of just the Darzalex, in addition to the infusion time for the IV premeds.

So, you go through all of that, and it ultimately did transition down to a 90-minute infusion for the Darzalex, but still, that day was sunrise to sunset. Because after that treatment, I'd get back in the car, the Benadryl would wipe me out. My wife would have to drive us home back in that LA traffic. It was absolutely grueling.

And it really was such that we had to schedule our life — our professional, our family, all of aspects of our life — around treatment because it was so consuming. And that treatment interval was weekly, then bi-weekly, and then ultimately evolved to monthly therapy. So, it was all-consuming.

So, that was those first two years. And it just meant countless IV sticks, it meant the time, and it really required a major shift in our life priorities, just to have to schedule our whole life around treatment, which was pretty grueling. We're thankful for the results, but we actually paid the price in what it meant on our quality of life and experience.

Yeah, yeah, I believe I can imagine. Thankfully, I've not gone through that or experienced anything remotely like that, but I believe I can imagine that. It sounds grueling, and thanks for sharing that. We'll get back to you about what it's like for you today, which we know is significantly different than that. Right.

But before we do that: Cathleen, do you want to similarly tell us about the beginning of your journey, what you were diagnosed with, and how that was for the period of time leading up to where we're going to pick it up today?

Bergin: Sure, so I have some similarities with Todd, but I have some differences as well, and my diagnosis path was definitely different than Todd. His was sudden, mine was 5 years of symptoms where no one could identify what was going on until, I went into a little bit of a crisis, and all the pieces to the puzzle came together.

So, I was actually diagnosed with myasthenia gravis In 2020 after 5 years of having these awful symptoms of fatigue, loss of voice, slurred speech, difficulty swallowing. It came to a head during the Covid time, which wasn't the most convenient time. I actually was working at argenx, preparing for their first launch of efgartigimod alfa, called Vyvgart, which actually treats myasthenia gravis. So, I always say I was on a blessed path in many ways.

At the time, the standard care was just to control the symptoms, not to address the underlying cause. And so, it was the great steroids: acetylcholinesterase, IVIG (Intravenous Immunoglobulin), plasmapheresis: all of which I didn't really care to engage in. As a nurse practitioner in hematology, oncology, and neurology, I have definitive ideas on what I will tolerate for treatment and what I would not.

But unfortunately, Vyvgart was not approved, and I needed to start on a therapy, as I was progressing. So, they started me on 60 milligrams of steroids a day, which, actually, unfortunately for me, the side effects of the steroids were actually worse than the myasthenia gravis itself. But it was keeping me going. And, fortunately for me, six months later, Vyvgart  IV was approved, for which I was able to get on pretty quickly with my diagnosis.

So, it was 10 milligrams per kilogram IV. It was given over an hour with an hour observation. It was four weekly infusions followed by a rest. And you would determine the next treatment based on the return of symptoms. So, we had individualized dosing. Not everybody gets treated with the same cadence. I'm actually four weeks on, seven weeks off, and I tolerated it very well.

It took me almost an hour to get to the infusion center where my specialist was. So, the turnaround time between leaving my house and my return could be six, seven hours in a day, depending on how jammed the infusion center was, which often it was. They constantly treated patients right through lunches and breaks and tried to keep us moving. But it was six hours on average and sometimes longer.

And for my family, it did impact everybody because they didn't want me to travel myself to get treated. I was pretty tired at the end of infusion. And so, my husband was able to drive to and from all the infusions for me. I'm appreciative of that. He was retired, or semi-retired, so it actually was able to work better for us. But, as you heard Todd say, many families don't have that option.

So, it was a lot of work and a long day, and I did it on Friday so I could recover on Saturday and Sunday. And the company was great in accommodating me, but again, not every patient has that ability. So, it impacts everyone in your life.

Yeah, again, I can imagine, and thanks for sharing.

Charles, before we later talk about the seat that you sit in there as Chief Medical Officer at a biotech provider company, I'd like you to, if you don't mind, reflect back on some of the earlier parts of your career, particularly as a medical provider. As I understand it, you are a former cancer surgeon.

So, as you look back, what do you recall about what it was like to be faced with patients and the kinds of diagnoses and scenarios of the types that Todd and Cathleen or others might describe — your thoughts about what that was like, and the options for them [the patients], and how you felt about that as a provider?

Theuer: Yeah, thanks, Tom. Well, you know, Todd’s and Cathleen's journeys are so meaningful because they mirror a lot of what I was going through as a journey through cancer care on the other side as a cancer surgeon.

I was a surgical oncologist or cancer surgeon in the late 1990s and early 2000s. At that time, as we looked at patients and offered them treatment options, it was really all about efficacy. We didn't have a ton of options, and so, for instance, especially in surgical oncology or medical oncology, it was all about, does a drug increase survival?

And for instance, we would have trials, and if a drug improved survival by two to three weeks, that was a huge advance. And there really was no discussion about what the toxicity profile of the drug was;  it was all about efficacy. And patient experience or patient quality of life was a distant third concern.

And it did reflect the fact we didn't have a ton of options. This was the era of chemotherapy. Chemotherapy inhibits the division of every cell in the body, including cancer cells, which is great, but also includes your hair follicles, your GI tract, and especially your bone marrow. And so, patients on chemotherapy have a lot of toxicity. They get a lot of infections.

What I was doing on a weekly basis, to Todd's point: Every Friday, I would be putting central lines into patients, because many patients couldn't even have peripheral IVs. And so, we had to do central lines to allow central venous access to allow them to receive their chemotherapy.

That inherently has its own risks, including the catheter risk. Sometimes they clot, sometimes they get infected. And so, even administering a therapy had complications for patients. The chemotherapy caused infections in cancer patients.

But even in autoimmune diseases, which Cathleen experienced, we were sometimes giving what I'd say “low-dose chemotherapy” for autoimmune diseases. A steroid is, in essence, an immunosuppressant. Sometimes that's not enough. That alone has side effects, as Cathleen shared. But sometimes we'd have to use low-dose therapy, like Interferon, to further suppress the immune system, which, as you can imagine, had further toxicity issues.

So, it was really an era where the options for patients were limited. It was so focused on efficacy because that was seen as the major advance. And we needed to move into a new era where toxicity was going to be minimized, and then also patient quality life would be maximized. And fortunately, we were able to make that transition with time.

Yeah, yeah, that’s good, and we'll hear more about that.

Perhaps you've covered this, but I'm going to ask if you have additional flavor to add to this. Besides the obvious of wanting cures back in those days, if you could have waved a magic wand about the patient experience and said, if we could move one thing forward, I'd choose, I'd start here: What might you have said in those days?

Theuer: Yeah, I think the biggest thing was trying to avoid the complications of treatment. You know, when you administer treatment, it in itself has side effects. When you have to, for instance, put in central lines into patients, that has side effects. So, I think minimizing the complications of treatment was really a goal of a lot of cancer physicians at that time.

Right, right, right. Well, thanks for that.

And I believe that makes a good transition back to you, Todd, about some of the ways in which the advances have arrived. Can you tell us about what some of those are, especially on the transition to the subcutaneous front, and what that has meant for your treatment regimen and everyone around you?

Kennedy: Yeah, for sure. I'm so grateful that, as Charles was mentioning, we are in this new era where it's not just about efficacy. We've got — and that's not just a distant desire, it's reality for now. I can share how that reality has played out for me.

Because everything changed, really, in that patient experience I described earlier in the first two years with the introduction of Darzalex Faspro, so the subcutaneous version. I was really grateful, as I described, to J&J for that original innovation of daratumumab. But also, very grateful to Halozyme, Charles' company, for the innovation of the hyaluronidase that is the Faspro component that really transformed my patient experience and allows me now to plan my life first and then schedule treatment around that.

Because now, versus what I described before, I take the premed at home. Since the Darzalex, that really critical anchor component, is now sub-Q, we don't do IV premeds.

I don't even take the Benadryl anymore. But I take the Tylenol at home beforehand. And I'm past the steroids, so we don't do any IV dexamethasone. Thank goodness. As Cathleen described, the steroids are a horrible component of treatment.

And so, I get to see my doctor now at 9, I'm up to the infusion center at about 9.30. The pharmacy time to prep everything and send it back down is much faster. They give me a three-to-five minute shot in the belly. No more fighting, no more trauma for me or the nurses in trying to set those IV lines. I've given them a plenty good target in my belly to give me that shot.

And it takes three to five minutes, I'm out the door, I'm home. Instead of that sunrise to sunset, it's like a two-hour door-to-door experience now. So, you can imagine, not only do I still have the efficacy and the tolerability, but I've regained so much more of my life in an improved patient experience.

And as I mentioned, I got a Darzalex Faspro shot last Friday. And I was talking to my care team, and I said, “You still call it Faspro Friday?” And they said, “Oh, yeah, because we can route so many more people through here than in the olden days,” when I'd be sitting in a chair for three to five hours.

You can imagine the capacity improvement if they can just burn me in and out of there and see that many more patients. So, it really is something that's been transformative to me, but also to so many of my fellow myeloma patients and other patients that have been able to move from the time burden and the challenges of IV to subcutaneous.

 In fact, I was thinking; I tried to do the math on this. Remember, the first two years were IV, and the last six years have been sub-Q Darzalex. And if you just did that math: If I had had IV that entire time, that would have been 100 more hours spent in an IV chair. Now, because of the sub-Q, the Darzalex Faspro, I've been able to spend [that time] with my family, and in my job and doing all the other things that are important to me in life.

So, it’s a really, really big deal. It's much more than convenience; it is a transformative experience. And that's why, when they do the research and they say, hey, what do you like, patients? Do you like IV or sub-Q? You know, 90-plus percent say, yes, give me the sub-Q. Why wouldn't you? I mean, seriously, why wouldn't you want that? So, it's a big deal. And you can see from that experience, it just changes so, so much.

Yeah, it sounds remarkable. And I know that one of the things we're going to talk about in a bit is some of the work you've been doing in those saved hours doing other things than sitting at IV centers. So, we'll get to that on the patient and research advocacy front.

But before we do that, Cathleen, how about picking up the thread for you in terms of how the treatment regimen and results of that have changed for you.

Bergin: Yeah, absolutely. And Todd, I love that he said 90% of the patients would say, yes, I would want sub-Q. There's still variation in some patients' needs. I will tell you that. I was on Vyvgart IV for three years. So, we were a little bit behind with the sub-Q formulation for myasthenia gravis. When Vyvgart Hytrulo was launched: it is a pre-filled self-inject, or a Hytrulo healthcare provider-administered injection. Flat dose,1,000 milligrams, 5 cc's. Thanks to the hyaluronidase technology, they were able to make that transition.

And I do say it's really important to keep in mind that patient preference is important in collaboration with them because some patients like their IV. I didn't jump right away. I was on the IV for six to eight months after the launch of Hytrulo because I was doing so well. So why would I change something that I rocked the boat, right?

So, this is where some of the variations — because, really, theoretically, in my mind, it should be 100%, you know, 100% no-brainer. But there are a lot of factors we do have to keep in mind. But factors change. Life changes.

And so, two reasons why I made the jump once the pre-filled syringe came out. First of all, Hytrulo came out, healthcare provider-administered first.: And that didn't change much for me. It would have gone from an hour infusion and an hour observation to a 30-minute, to an up to 90-second injection and a 30-minute evaluation. But I still had to travel an hour to and from my spot. So, I stuck with IV.

But, once pre-filled syringe came out, everybody was shocked [that[ I waited a little longer. Until two things happened: one, my veins did not cooperate. You heard Todd, it's not fun. Multiple injections to try to start an IV started to happen. And two, my job in covering the U.S. with my team increased travel tremendously.

For those two reasons, and life changes for everybody, those were motivators to change to pre-filled syringe. I really wanted to treat wherever I was when I needed treatment and not have to worry about it. [Instead of] rushing on a plane, a train, or in a car to get home on Thursday night to get into the clinic so that I can either get injected or the IV formulation, I could actually take the medication with me and treat where I was.

And so, unbelievable freedom for me; it actually helps me stay on schedule a lot easier. It stopped the total impact to my family of having to come with me to the clinic. It was just an amazing experience and life-transforming. It really means that I could fit my treatment into my life and my schedule, instead of building my life around treatment. And you can't even describe the amount of time you get back, and what that means to us.

Gotcha. Well, thanks for sharing, and I'll be coming back around to you, Cathleen, to ask more about any impact that your own experience has had on how you approach the patients that you encounter in your work scenario.

Before we do that, Charles, I'm going to turn to you and ask you about how the folks in your work environment, including yourself, think about the patient population out there.

So, it might help our audience to understand, if you could first briefly describe where Halozyme fits in the ecosystem of contributing to the kind of solution and result scenarios that Todd and Cathleen are describing. But, then beyond that, maybe talk a bit more about how the patients — how thinking out toward the patient experience does inform the way you and the other folks there think about the challenges and the problems to be solved.

Theuer: Sure, I appreciate it, Tom. Yeah, I think I'd pick up initially on a point that Todd made that I think really puts in perspective how subcutaneous dosing can benefit the patient. Todd mentioned he had to take four drugs in order to initiate his therapy for myeloma. Three of them were already given by a non-IV route: two orally, one sub-Q. And so, when Darzalex converted from IV to sub-Q, that was the last chip to fall, if you will.

And now, when patients with myeloma start therapy, they don't even need an IV anymore. And if you had made that statement, say, even 10 years ago, that you can start major therapy for cancer — four separate drugs —and not need an IV, people would have said, “That's not possible.”

So, we've seen this evolution that Todd and Cathleen have described, which is really quite amazing for patients, that you can go from dosing over hours to literally dosing just over minutes, or sometimes even seconds, in the case of the therapy that Cathleen is taking. And that's a huge benefit for the patients, as we've heard. What patients want is their time back, and sub-dosing allows them to get their time back.

The other thing that we always think about at Halozyme is that we believe — and there's data that supports this —that, when you convert from IV to sub-Q dosing, the drug is actually safer for the patient.

So, we talked about three things with respect to a patient: efficacy, safety, and then the patient experience. And we think sub-Q dosing actually could potentially help all three categories. Clearly, it helps the patient with respect to taking their life back, getting time back by going from IV to sub-Q. But we also see safety benefits. For instance, Darzalex, the drug that Todd is taking: When patients receive that intravenously, sometimes that first dose, because they get all that drug over a very short time period IV, you get infusion-related reactions: shaking chills that are very discomforting to the patient, and sometimes can be dangerous.

[Along with] Darzalex IV to sub-Q going from hours to minutes in terms of administration, the side effect of infusion reactions decreases by threefold because of the way the drug is absorbed when it's given sub-Q. So, we've seen safety benefits.

With one drug, a different drug that we haven't discussed today called Rybrevant, changing the administration from IV to sub-Q actually improved the overall survival of the patients who received the drug. So, for us, dosing from IV to sub-Q is about patient quality of life, but it's also about improving the benefit-risk profile for the patient who receives a given drug.

Gotcha, yeah, thanks for that.

Cathleen, I know that not only from your own experience, but even in the role that you're in, the clinical field work that you head up: How has your experience informed the way you think about encountering patients and the kinds of challenges that the company is trying to solve for them? How does that impact the way you approach your work now?

Bergin: It's impacted me tremendously in a positive way. I am the voice for the patient since I've walked through the journey. I understand. I don't think I've had any less blips in the road or barriers that have popped up than anybody else, and I understand that.

And the voice of the patient is extremely important, especially in the development of therapies that make a difference for us, right? And it's really important to listen to the patient. All companies say they're patient-centric, and they are.

I would just say that argenx has done a really amazing job listening to the patient before they even set up clinical trial. They actually asked the patients before they set up the trial, “What do you want to see in the trial?” That's an amazing thing that they did.

And patients said they wanted to stay on their supportive therapy because, if they went to placebo, they didn't want to get into trouble. They also said they want seronegative patients without the antibody but have a diagnosis of myasthenia gravis to be included in the trial because they're always excluded, and they don't have an option. And they also wanted the drug only when they needed it.

So, based off of that, argenx was able to develop efgartigimod [alpha] In that fashion: individualized dosing for everybody. So, they get the drug when they need it. Patients are on supportive therapy. We did not get seronegative approval, but Japan did, and we continue to work towards that and look forward to that as well. So, I do think that taking the patient's wants and needs and trying to align them has really been key for us.

Another example is Vyvgart, or efgartigimod alpha, [being] approved for CIDP [chronic inflammatory demyelinating polyneuropathy]. That disease is a different neurologic disease. It has heavy burden of disease. And it [Vyvgart] is given weekly. And so, listening to the patient, argenx heard loud and clear they were not interested in IV formulation weekly, and they went right to the Hytrulo for approval, which is what was approved for the weekly treatment of CIDP.

Yeah. Well, thanks for sharing that. And, of course, for mentioning the necessity and the real criticality of listening to the patients.

I'm going to turn to Todd, who has made something of his life's work being that voice for himself and for others. And so, Todd, do you want to tell us about [that], including those hours that were freed up to be able to do some of this — what you're involved in and why it's so important?

Kennedy: For sure. And I thought, as I retired, that I'd be spending time at the beach or on a golf course or something, but this has become a passion project, for sure — to try and help partners do better for patients and then have patients have a better life as well. My kids say that we have failed retirement, but my wife and I feel like this is, how better to spend your days than helping others?

And like you said, Tom, the goal is to be the voice of the patient — and Cathleen has spoken to that as well — to people that need to hear that voice. And that can be the research community, so that our trials are not looking, as Charles had said, only at efficacy and tolerability, but really putting emphasis on quality-of-life outcomes.

And really recognizing the value of the patient experience and being a voice of patients to the broader drug development community regarding coming to the market with key innovation, not only in your drug, but also in how patients get it. And then being an advocate for patients as well because there’s really a need to educate and empower patients so that they understand their options and are having a really informed conversation with their care team.

You know, we talk about shared decision-making and asking their care team, what are my treatment options that are best for me? And tell me more about the efficacy, tell me more about the tolerability. Empowering patients to ask, too, about, so how is this delivered? And how long is this going to take? And how is it going to impact all those things I want to accomplish?

Because so many doctors — Charles talked about his experience and, understandably, when we didn't have a lot of different options and it was all about efficacy — doctors would say they're very focused on what is the matter with you. But they're less informed about what matters to you. They don't really have a clear understanding of what's important in your life.

And there's a difference between what is the matter with you and what matters to you. So, trying to encourage patients to speak up and tell their care team about their lives and how they're trying to manage life and treatment at the same time is really important. And I think that we don't have that old patriarchal system where the doctor says, this is what you're going to get, and you're going to love it.

A friend of mine likes to say that the physician is the explainer but, ultimately, the patient is the decider. And I think that's really important; that's where we have moved towards, and that's a good thing.

So, work hard to make sure that patients can make decisions based on their full understanding of that comprehensive picture of their options. And I think it's reasonable for patients now. We're not in that old era where it's just about, I'm going to go through brutal therapy to save my life or extend it by months. I think in many diseases, in many different cancers, it's reasonable to expect, thank goodness, efficacy, tolerability, and quality of life, and a reasonable patient experience.

So, we encourage patients to set that expectation and ask for it.

Well, I appreciate, obviously, your willingness to take it forward and pay it forward, so to speak.

I like to end these conversations — or maybe end is not the right word for it, maybe it's just look forward, a transition to the future — with an open-ended question:

As we look out over the horizon, whether that's a near horizon or a far horizon, and we think about the patient experience, the curative nature of things, the regimen, the caregivers, the medical providers, the families. If these advances, such as the ones we're describing in the transition from IV to subcutaneous, take hold and other sorts of advances, what are your hopes and dreams for what a future state might look like and what are some key ways we get there?

 I'll just open it up and see what your thoughts are about that.

Bergin: I could build off of what Todd was saying about advocacy. I'd love to see the patients — we have more of a collaborative relationship with our physicians today, which is absolutely true, but we're not there yet with all patients. Especially at the beginning of their journey, they're just looking for guidance, right? But patients will ask questions and educate themselves and become more advocates like they want, and I think that's where we would like to go.

As a nurse practitioner, I always considered the best options for patients. I thought about clinical presentation and the issues that they face, and of course, coverage, which is a reality in life for us as well. But I always included the patient in the decision making. So, we're getting there.

What I've learned is that patients want choices as long as multiple options are safe and efficacious, and they're equal. They would rather [have] less frequent dosing and [more] ease of administration. Those are two things, okay? So, we're never going to trump safety and efficacy. None of us wants that. But just ease to adapt to their lives, in administration is really important, as well as being able to live optimally, is really where they want to go.

So, sub-Q provides the ease and convenience for the patients to live their lives while they optimally manage their disease. And I do think that developing routes of administration, less frequent dosing, and any apparatus, such as an autoinjector — all of those factors will make things way easier for patients to manage and live versus surround their life around treatment.

Gotcha.

Theuer: Yeah, I can just pick up on two of those themes that Cathleen and Todd talked about. The patient is the decider is such an important concept. And the more options we give patients, the better the decisions that they can make. At Halozyme, our focus is converting IV therapies to sub-Q, And even high-dose therapies, like Darzalex, can be converted into a sub-Q dose. It can be given literally over minutes, as Todd discussed.

We're trying to now shorten that time frame even to seconds. One of the medicines, the Cathleen profile that she's taking, can be given in less than a minute. We're looking to use hyper-concentration technologies to complement our enhanced hyaluronidase to give doses in such small volumes, they potentially could be given, as Cathleen mentioned, by a simple autoinjector, literally over seconds. So, that's where we see the future. Give patients even greater benefit by continuing to compress administration time and still see those safety benefits.

And then the other big thing we're working on are the therapies we've really been able to see productively convert from IV to sub-Q: antibodies, or biologic therapies like antibodies. But there's a whole host of other therapies we feel that that technology could be applicable to.

I'll give you just one brief example: antibody-drug conjugates [ADCs]. These are really potent therapies where the antibody actually has a payload, so you can imagine they can be quite toxic. We're wondering, can we convert those from IV to sub-Q and see the same safety benefits in addition to the administration benefits by giving those sub-Q with our technology?

So, those are all things we're working on for the future with the overall benefit being to improve the patient experience and improve the patient benefit-risk.

Gotcha.

Todd, anything you want to echo there or add to?

Kennedy: I think what Charles described and what Cathleen described is, it’s that new era. And I think patients like Cathleen and me, and the thousands of cancer patients and others, are just so grateful for this innovation.

I mentioned that my disease has been historically considered incurable. And the top myeloma experts in the world got together about two weeks ago, and they said, we've got to stop using that word incurable. Because there is a fraction of patients that are currently cured, and that fraction is increasing.

We are coming up with new treatment options. It's a very good time to have a pretty crummy cancer. But we're moving towards cure, we're moving towards new treatment options, including antibody drug conjugates, as Charles mentioned. And we’re getting not only better efficacy, but we’re also getting better tolerability, and we're getting better quality of life.

So, it's a really great time to have this disease, and we're grateful for all the developers and partners that are making that happen.

But my request in this regard is, again, don't forget about that patient experience. Because, as we've described, hopefully in a compelling way, it's not just a matter of convenience. As Charles talked about, there's a safety component. There is an impact on quality of life and productivity as well.

To the developers out there that are coming up with new treatments for myeloma — and there's a lot of things in the pipeline — don't start researching sub-Q as an option late in the life cycle. This isn't a lifecycle play: This is a life play for people like me. Invest in subcutaneous delivery options so you can launch with sub-Q. And then that gives me, Cathleen, and the countless other patients, hours of life back.

So, that's what our big request would be. Launch with it. Because, like I said, too, patients know that this delivery option is out there. And if you come with IV, and your competitor has sub-Q, that's going to be a differentiator for the sub-Q player. So, it's not only a good to have; it is an impact on the patient experience, for sure, and potentially outcomes as well. But it's good business, for goodness sake, you know? It'll give you a competitive advantage on growth and market share as well.

So, that's my plea. Just hear the patient voice in all of your decision-making throughout the product lifecycle and think about efficacy, tolerability, quality of life, and the patient experience. And I think sub-Q — and Halozyme has been a real leader in that — so we're really grateful for the progress. And thanks for the opportunity, Tom, to tell the story.

Yeah, well, I was just about to say thanks to all of you for sharing your insights. I appreciate the passion coming through in all of you. Clearly, Todd, yours always does, and it did right there once again.

Again, thanks to all of you, Todd and Cathleen and Charles, for joining today, for sharing your insights with our Drug Delivery Leader audience. And to that audience, I want to say thank you for joining for another episode of In Combination. And we'll see you next time.