2026.10.10 | GP | Biotech | Concentric Analgesics Vocacapsaicin Phase 3

Viewpoint:

Academic KOL - Physician

Moderator: Atif Siddiqui (AS)

Matthew W Swisher (MWS), Associate Clinical Professor of Anesthesiology - UC San Diego Health

SUMMARY

Overview

The discussion assessed vocacapsaicin, a locally administered capsaicin prodrug being developed for postoperative pain. The expert specializes in regional anesthesia and acute pain medicine and treats approximately 100–200 surgical patients monthly across several noncardiac specialties.

Vocacapsaicin could complement multimodal analgesia through a non-local-anesthetic mechanism. Its potential advantages include prolonged pain control, reduced opioid use, compatibility with nerve blocks, and avoidance of motor weakness. The expert estimated that more than half of surgical cases could benefit from an additional analgesic mechanism.

Key Insights

Opioid-free recovery was considered the most meaningful endpoint, followed by total opioid consumption and then pain scores. The bunionectomy pain reduction was viewed as modest, although the opioid-free result was more compelling. In knee replacement, the pain benefit was not considered impressive, but the reduction in opioid consumption was clinically meaningful. The lack of comparable efficacy at 60 mg versus 36 mg was considered unusual and raises dose-response questions. Smaller, localized incisions appear better suited to surgical-site infiltration than extensive procedures such as abdominoplasty. Lack of motor weakness could provide a major advantage over local anesthetics, particularly for extremity surgery. Adoption will depend primarily on efficacy and local safety, especially wound healing, tissue injury, and infection risk. A price below $500 per procedure was viewed as important for hospital adoption.

Clinical Data

Surgical model

Findings

Expert assessment

Bunionectomy

A 147-patient Phase 2 trial improved 96-hour resting pain and reduced opioid use. Opioid-free rates were 26% versus 5%, while consumption fell by 50%.

Pain improvement was modest; opioid freedom was the strongest result.

Knee replacement

An initial 54-patient study at 5–15 mg showed no pain benefit. A later 187-patient study succeeded only at 36 mg, not 60 mg.

The inconsistent dose response requires clarification.

Abdominoplasty

A 54-patient Phase 2 study at 10–15 mg failed.

Large treatment areas may dilute effectiveness.

Ventral hernia repair

A 24-patient study produced an early efficacy signal.

Evidence remains preliminary.

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Competitive Landscape

Approach

Positioning

Limitations

Vocacapsaicin

Potentially durable analgesia without numbness or motor impairment

Efficacy, optimal dosing, and wound safety remain unresolved

Standard bupivacaine

Established and operationally simple

Limited duration and possible motor weakness

Liposomal bupivacaine

Intended to extend local analgesia

Surgical-site efficacy remains unconvincing to some clinicians

Multimodal systemic therapy

Current standard background treatment

Often does not eliminate opioid requirements

Quantitative Insights

Metric

Expert view

Preferred study window

Generally 24–72 hours; up to 14 days for knee replacement

Clinically meaningful knee pain reduction

Approximately 30% minimum

Potential use after compelling bunionectomy data

50–100% of eligible patients

Regulatory evidence

At least two surgical models plus a broad open-label study

Adoption-oriented price

Below $500 per procedure

AS: It seems like we are on. Should we go?

MWS: Okay.

AS: Yes. Great. Hello everyone and thank you for joining this call. My name is Atif Siddiqui and I'm an analyst at Guidepoint Insights. Today's call is going to focus on analyzing Concentric's phase 3 ready asset, CA-008 or Vocacapsaicin for post-operative pain management. I'm happy to be joined by Dr. Matthew Swisher to discuss this topic in detail. Thank you Dr. Swisher for taking out the time to do this. And before we begin our discussion on the topic, can you please briefly introduce your professional background and experience treating post-surgical pain management cases?

MWS: Yes, of course. I'm an anesthesiologist. I specialize in regional anesthesia and acute pain medicine. So I do this on a daily basis. Treat acute pain. I do a lot of nerve blocks and then multimodal analgesia for post-operative pain.

AS: Understood. And can you tell us roughly how many surgical or post-surgical patients do you see in a typical month and what cases might constitute a majority of your practice?

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MWS: I'd say it's probably 100 to 200 patients per month on average. And then I do all types of surgery except for cardiac. So we'll cover a lot of orthopedic surgery, urology, general surgery, colorectal, plastics, ENT. So pretty much everything.

AS: Moving to Concentric Vocacapsaicin, can you tell us a bit about this novel formulation of Vocacapsaicin and what sort of indications do you see it mostly working in or mostly being adopted in if it gets approved?

MWS: Yeah, I don't have any personal experience with it. I wasn't involved with any of the studies that have been ongoing, but I've only read about it. It sounds like it's a local administration of a prodrug of capsaicin, and it has a wide range of applicability if it works well. So it's essentially any surgical site, any surgery that involves any sort of surgical incision, it would be helpful. Sometimes with local anesthetic-based things, you're limited because the patients are already giving a nerve block, so you can't really give additional, or there's concerns about giving additional or different types of local anesthetic. So obviously, this would not interfere with that, so it can be applicable to a lot of different types of surgical incisions.

AS: And considering the existing multimodal analgesics, including local anesthetic nerve blocks, where do you see which currently unmet need do you see this novel formulation solving?

MWS: Well, the unmet need would be mainly a different type of mechanism of action for surgical site pain. Obviously, any local anesthetic is limited in duration, and even with the lipid emulsion type local anesthetics, it's unclear if they even work at the surgical site to any appreciable extent. A lot of people with Exparel and other liposomal bupivacaine aren't really sold on the fact that it has a significant efficacy when you administer it at the surgical site. So because of the different mechanism of action, I think there's a wide range of surgeries that it could potentially be useful if it's truly efficacious.

AS: And what percentage of your pain management cases would comprise this sort of subgroup which needs something apart from the liposomal bupivacaine or other treatments that you mentioned?

MWS: I'd say probably at least 50%. Yeah, obviously the distal extremity surgeries are helpful, but even truncal surgeries like hernia repairs and things like that. Any standard local anesthetic doesn't really do a significant amount at the end of the case. So I'd say it's probably greater than 50% of surgical cases that we do.

AS: Understood. And now moving to Vocacapsaicin results first in the bunionectomy trials. So it's phase two randomized trial with 147 patients that was published in 2024. It met the primary endpoint of decreasing resting pain AUC over 96 hours compared to placebo. What are your thoughts on the difference in the pain intensity that they showed with this compound? And also maybe you can put in the... So they've also shown the reduced use of opioids in this study. So what are your thoughts on these 2 data that they showed over there?

MWS: I see. The end point is, well, you know, I don't know the duration of action that this product is supposed to use, but a 96-hour end point is probably not the best end point to use for something that might not be working for 96 hours, but I don't know the duration of action of what they expect. So when they saw a reduced pain at rest at 33% versus placebo.

AS: Mm-hmm.

MWS: I would say that's not very impressive. I'd say you'd probably want to see greater than 40% reduced pain at rest and especially with activity. But that could have just been hampered by the 96 hours in duration that maybe if it's not expected to be working past the 48-hour mark, that probably is not a great end point to use. And then versus when your primary comparator is placebo, also not a super strong primary endpoint because obviously the standard now

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would be someone giving bupivacaine standard bupivacaine at the end of the case so a comparator between this prodrug, this medication and standard procedure which is probably infiltrate with 0.25% bupivacaine would probably be a better comparator and then when they looked at opioid, post-operative opioid use, and then they note that 26% did not receive post-operative opioid for analgesia versus 5% of the placebo, that would be a stronger end point. So you know, a reduction from 26% to 5% for someone that did not require any post-operative opioids would be a stronger end point in my opinion and then they looked at reduced opioid consumption over the first 96 hours, reduced it by 50% in total, less important than that second outcome which would be opioid freedom outcome. So I'd say that second outcome, even though that probably wasn't their primary endpoint, was probably a stronger endpoint of 26% versus 5% placebo.

AS: I understood. And so one point over there, so the comparison that they draw was on the background of standard multimodal analgesia. So I don't think it was just placebo. I think it was placebo and concomitant multimodal analgesia.

MWS: Right.

AS: So would that make any difference to the kind of comparison you would make? And you drew the 18% reduction of placebo while both of the treatment arms, placebo and the active treatment group, they did receive multimodal analgesia, including bupivacaine as well as, I think, rescue medications or the Ketorolac as well. So what are your thoughts on this, that they didn't actually just compare it with the placebo, that they did have background running concomitant multimodal analgesia?

MWS: Right. That makes the comparison more real-world applicable. If obviously patients are getting standard of care and they're getting pharmacologic multimodal analgesia, that makes it slightly stronger. And when your placebo is, you know, obviously simply the medication that you're injecting during surgery, I think that makes it stronger. Yeah.

AS: Understood. And you mentioned about the durability or the time duration that they followed. So I want to ask you what minimum durability would you want to see with this analgesic or any other upcoming post-surgical or perioperative analgesic? And maybe you can, if you could tell me what's the more critical period in terms of if we talk about opioid consumption post-operatively?

MWS: I think durability, is that what your first question was?

AS: Mm-hmm.

MWS: Like how long it lasts? Yeah.

AS: Yeah.

MWS: I mean, for every surgery it is different, but for a bunionectomy, obviously 96 hours is a decent time point. That's when you'd expect the most amount of pain and the most amount of opioid needed during the first 96 hours. For something like a total knee arthroplasty, the duration of pain is on the order of longer, 5 to 10 to even longer... then you'd want to see a longer duration. But when people are studying these perioperatively, they're not going to use a 2-week endpoint of pain unless it's a medication that you're taking for 2 weeks. So for something that you're giving at the surgical site 1 time in the operating room, I think an endpoint of anywhere between 24 and 72 hours is probably the most appropriate.

AS: Mm-hmm. In terms of... if we talk about pain intensity, obviously these 2 would be correlated, but the endpoint you mentioned would be the same in context of the pain intensity as well as the opioid consumption if we were to monitor both of these parameters?

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MWS: Yes. Yeah. I personally like opioid consumption and opioid. I think the strongest one is opioid freedom. So percentage of patients that don't need to require any opioids with the active comparator. I think that's personally the strongest outcome. But when you design these studies and you want a positive study, you're mostly going to be looking at pain intensity and NRS scores. And then the other one would obviously be opioid consumption. So I think opioid freedom is the best primary endpoint that has the biggest impact for people that are reviewing studies. And then number 2 would probably be opioid consumption. And then number 3 would probably be pain scores.

AS: Understood. Now, coming to Vocacapsaicin's total knee arthroplasty phase 2 trials, the initial smaller phase 2 trial with 54 patients that were randomized to 5, 10, and 15 milligram dose arms showed no detected pain relief, while in a subsequent larger trial with 187 patients that were randomized to placebo or higher treatment groups, 36 and 60 milligram dose arms, it met its primary endpoint in only the 36 milligram dosing group, reducing both the resting pain intensity as well as opioid consumption. And it lasted durably up to 2 weeks post-surgery. Results that were reported by Concentric only mentioned the 36 milligram arm consistently performing better than the 60 milligram one. So first, I wanted to ask you that, given all these dosing arms and the results that came out in the TKA studies, what do you make about the therapeutic index of Vocacapsaicin or finding the suitable dose of Vocacapsaicin that might be beneficial in TKA cases?

MWS: When they settled on the 36 that showed their strongest result, is that what you're asking?

AS: Yeah, that's where they showed the strongest and all the other ones, including the earlier study with 5, 10, 15 or the later study with 60 milligram. It's just a 36 milligram which reported any significant benefits. So based on these, what do you make of the therapeutic index or the therapeutic dose of Vocacapsaicin in TKA cases?

MWS: I think it's unusual that a higher dose of 60 milligrams didn't show either at least equal results to the 36 milligrams. But I think otherwise, the data makes sense to me. Obviously, they ramped up to a dose of 36 milligrams compared to the lower doses and found a better analgesic result. It's just odd to me that 60 milligrams didn't show a similar result to the 36 milligrams, which is what you'd expect out of a kind of plateau effect.

AS: Understood. And talking about the results that they reported from the 36 milligram arm. So they reported about 18% reduction compared to placebo over the 96-hour post-operative period. And also it lasted durably out to 15 days post-surgery with 15% reduction being shown. So what are your thoughts on this pain reduction that they show? How compelling does it look?

MWS: The 15% to 18% is that what you're asking?

AS: Mm-hmm.

MWS: I would say that's not for total knees, it's hard to show positive results given the duration and intensity of their pain whenever you do these clinical trials for these patients. So I'd say it's not impressive, but it is in line with what you'd see when you design an analgesic study for a TKA patient. But yeah, 15% to 18% is probably not very impressive, that's...

AS: And what would be the range that you would consider clinically significant over placebo in these TKA cases?

MWS: 30% would probably be the minimum thing that I would find significant.

AS: And again, if we talk about the pivotal time period or the sort of durability follow-up that you'd want to see in such treatments.

MWS: The durability for a TKA patient, I'd want to see a durability of a 2-week, probably overall 2-week, 14-day kind

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of type endpoint.

AS: Got it. And again, coming to the same opioid reduction or the opioid-free care. Sorry, opioid-free patient. So they reported a 30% reduction in this 36 milligram arm in opioid usage up to 96 hours post-surgery, which shot up to 52% from 96 hours to day 15. So how compelling does this reduction in opioid usage sound to you?

MWS: I don't think they reported... I'll check about the opioid-free cases after.

AS: If you could just give your thoughts on the opioid reduction, let's see.

MWS: Yeah, I'd say 30% to 50% is impressive. I would say that those are clinically significant decrease in opioid consumption. 30% to 50%, I'd say that's more impressive.

AS: And this one I don't think I found any sort of results on the opioid free but anyhow.

MWS: Yeah, AS: Yeah MWS: A lot of studies don't report that or they don't have that as their endpoints.

AS: Got it. So Dr. Swisher, so the Vocacapsaicin phase two trials in bunionectomy and total knee arthroplasty have used drastically different dose levels. In the bunionectomy trials used about 2.1 and 4.2 milligrams while the TKA phase two ranged up to 60 milligrams. Can you tell us what would you consider to be a safe capsaicin dose based on maybe what's seen with the Qutenza capsaicin patches? I know they are completely different formulations, but are there any major adverse effects that you see with Qutenza patches that might manifest in some way or form in a surgical wound application of this drug or capsaicin?

MWS: So I don't personally prescribe or none of our surgeons prescribe Qutenza. So I haven't actually... I don't have firsthand experience with the adverse side effects from that. I would expect.

AS: Can you tell us again, okay, so can you tell us what do you make of the drastically different doses that were used in the bunionectomy trial and the TKA trial of this drug, Vocacapsaicin?

MWS: Yeah, it's unusual that the bunionectomy trial used 4.2 and the TKA used 36 and 60. It would make more sense as a clinician to find a uniform milligram dosage irrespective of type of surgery. So I'd want to find a better... yeah, I think it would make more sense to find a uniform dosage.

AS: And can you tell us if there is any sort of difference in the amount of analgesia administered to these 2 different surgical cases? TKA and bunionectomy?

MWS: Oh, the type, say it again, ask the question again.

AS: Like, the amount of analgesia that is usually administered to patients undergoing these 2 types of surgeries?

MWS: Yeah, I mean, TKA patients tend to have more intense pain and then for a longer duration of time than a bunionectomy patient, although bunionectomy patients can have pretty significant pain over the first 48 hours usually.

AS: And do you see that MWS: TKA patients have a lot more pain?

AS: playing a role in the kind of different dosing that they've used for these 2 surgical trials?

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MWS: Yeah, I mean, obviously you would expect the bunionectomy patient to require less of your experimental analgesic. So maybe that's why they settled on the 4.2 versus the 36 and 60. So it does kind of make sense. Yeah.

AS: Understood. And so Vocacapsaicin also has done trials in abdominoplasty. It failed a phase 2 abdominoplasty trial with I think 54 randomized patients and a 10 and 15 milligram dosing. It also showed early efficacy signals in a small 24 patient ventral hernia repair surgery. So given all these different surgical trials and the target market size, which indication do you see being most relevant for Vocacapsaicin moving forward in a pivotal phase 3 trial maybe?

MWS: I mean, simply because it's a surgical site administration, so a more localized surgery like a bunionectomy or an extremity surgery makes more sense than getting a good result in an abdominoplasty or a ventral hernia. So something where you have, especially like abdominoplasty where you have pretty large incisions and then you're giving your medication spreading it out over a pretty large surface area and injecting it all over the place. My guess is that it probably won't work as well for larger incisions like abdominoplasties and breast reductions. It probably worked better for smaller surgical incisions like a bunionectomy.

AS: Can you talk about, if it shows kind of similar efficacy levels in a Phase 3 trial of bunionectomy, which patients or what percentage of your patients do you see prescribing this analgesic to given the existing standard of care?

MWS: What percentage would I prescribe it to? For which types of patients?

AS: In terms of, you talk about distal surgeries. If we take into account, if we talk about bunionectomy...

MWS: Yeah.

AS: Yeah.

MWS: Yeah, I mean, if the data is compelling enough, you know, I'd prescribe it for 50 to 100% of patients. That's my guess.

AS: And demonstrating efficacy in how many different models of acute pain and post-surgical pain, including bunionectomy, TKA, abdominoplasty, or hernia repair, do you see being required by the FDA for approving Vocacapsaicin as an intrasurgical analgesic?

MWS: So probably at least 2. So I would probably pick bunionectomy and something else. If they've seen decent results with abdominoplasty, that's usually a good surgical model. And then I would also still do a more of an open label study where you do many, many different types of surgeries. The FDA will usually probably want to see that as well to show safety and efficacy over a wide region. So an open label study in addition to 2 surgical models.

AS: And if they show that in 2 surgical models, what do you expect the FDA's labeling breadth for this drug to be if it shows efficacy in 2 different models?

MWS: You still have to do an open label study, because you wouldn't want to get FDA approved just for those isolated surgical things. So the FDA, in order to achieve FDA approval for all types of surgeries, you'd want to have the open label study. So you wouldn't want it approved for just limited types of surgeries.

AS: Now, Dr. Matthew, Concentric are building their thesis of Vocacapsaicin on providing durable TRPV1-mediated nociceptor desensitization without, you know, inducing motor weakness or sensory numbness. How mechanistically plausible does the idea seem to you? And also, how would you judge this drug's performance on this claim of no motor weakness?

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MWS: I mean, it would make sense that there wouldn't be motor weakness because it's not local anesthetic based. From a clinician's perspective, it's important to have something that works well that doesn't cause motor weakness, especially when you're working on arm or leg surgery, because obviously all the local anesthetics that we give with peripheral nerve blocks have an undesirable side effect of motor weakness. So it would make sense to me that I wouldn't expect their molecule to cause any distal motor weakness and that would actually be concerning. And it would be a big selling point over local anesthetics and things like liposomal bupivacaine that inherently cause a significant motor weakness.

AS: And what readouts do you want to see in order to judge its performance on this claim?

MWS: What data would I want to see?

AS: What data would you want to see for testing whether it has any effect on motor weakness or not?

MWS: I would say for like the bunionectomy study, if you studied that, I'd want a report of, you know, no degree of clinical subjective weakness to their toes or their feet post-operatively. I'd want that reported in the trial as well, but I wouldn't expect it. I wouldn't expect this medication to have any motor weakness.

AS: And what operational barriers do you see limiting the adoption of this surgical site infiltration therapy? Any sort of limitation, any sort of limiting factor you see over there?

MWS: I mean, it's 1, efficacy. If it works well, people will use it. And then 2, side effect profile. If there are surgical site wounds or damage, poor wound healing, or infections, that would limit its adoption significantly. But those are, yeah, efficacy and local side effects.

AS: And do you expect any additional sort of workload burden if we talk about preparation time or any pharmacy workflow or protocol standardization or any additional workload do you see being added with this medication?

MWS: No, I wouldn't anticipate significant. So just like any local anesthetic that a surgeon would infiltrate at the end of surgery, then obviously pharmacy would provide it for you. So there'd be work on the pharmacy side of things, but I don't think it would cause significant workflow issues during the operation. Mm-hmm.

AS: Understood. And what price range, Dr. Matthew, would be acceptable to hospitals or other surgical centers if this drug maybe affects or maybe reduces the length of stay in hospital stay? What if it does not have any effect on this?

MWS: It would be hard to prove a decreased length of stay. That would be difficult to see. Like you could, because a lot of the total knee patients are leaving the hospital in the US. And then most of the TKA patients are now leaving same day. So I don't think you'd ever be able to show a decreased length of stay with this medication. I don't think that would be possible.

AS: And if we take, obviously, if we take out that part, like what pricing do you see for making this drug competitive with the existing standard of care?

MWS: I would say it's probably going to need to be less than 500 in order to get adoption.

AS: Understood. Well, that seems to have covered everything that I had on my agenda for this call. Do you think we missed out on any important point, Dr. Matthew, that you'd like to maybe overall summarize it with?

MWS: No, I don't think so.

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AS: Great. Well, thank you very much, Dr. Matthew, for taking out the time and giving your thoughts on this subject. I hope you enjoyed our conversation.

MWS: Very good. Thank you so much.

AS: Thank you. Have a good day. Bye-bye.

MWS: You too. Goodbye.

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10/11/2026 at 11:28 AM UTC