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This medical industry feature titled “A Look at the Clinical Trial Data on a Recently Approved Treatment for Painful Diabetic Peripheral Neuropathy of the Feet“ is sponsored by Averitas Pharma.
You’ll be hearing from Dr. David Simpson, Professor of Neurology at Icahn School of Medicine at Mount Sinai.
As of December 31, 2020, the description of QUTENZA (capsaicin) 8% patch, has changed to QUTENZA (capsaicin) 8% topical system. This change in language is not reflected in this transcript because the video with Dr. Simpson was recorded prior to the change in the product description.
Here’s Dr. Simpson.
My name is David Simpson as you've heard I'm a neurologist with a subspecialty in neuromuscular disorders and clinical neurophysiology based at Mount Sinai in New York City. And today we're going to talk about a subject of great interest to me in which I've been working for quite a number of years both in terms of clinical research and clinical care and will focus on an exciting new medication called Qutenza for the high concentration 8% capsaicin patch and we'll discuss some of the data from clinical trials focusing on it's used in painful diabetic peripheral neuropathy.
What I show you here is the phase three pivotal trial so-called step study that in fact led to the approval of Qutenza in the treatment of painful diabetic neuropathy by the FDA in the United States fairly recently. It has been approved in Europe by the European Union several years ago for this and numerous other indications.
Now the study inclusion criteria are shown up on the top left and these were patients that were over 18 years old with a diagnosis of painful diabetic peripheral neuropathy for at least one year with the hemoglobin A1c below 11 percent and stable doses of pain medication for at least four weeks prior to study screening. They were required to have an average so-called NPRS numeric pain rating score over the last 24 hours of greater or equal to 4 during the screening period, remember that the NPRS scale of pain goes from zero no pain to 10 worst possible pain. Now you see the study design shown in the flow chart with patients randomized in a one-to-one fashion to Qutenza versus an inert Placebo patch and I'll emphasize that point because in prior Qutenza studies most if not, all of prior studies used a low concentration capsaicin patch as the control but here was a true inert placebo. Patients received a single 30-minute application of the Qutenza patch to the painful feet on each foot and then we followed for a period of 12 weeks with no further patch applications. The primary endpoint of the trial was the percentage change in the NPRS score over the previous 24 hours from week two through week 8 and then there were a number of secondary endpoints including the average daily pain score, responder rates, sleep interference, time to response and global scales and quality of life scales.
Next move to the data showing us the primary endpoint result and the average change in pain on the NPRS score from baseline through week 12. And you see the decline in pain in the Qutenza group in purple versus the placebo group in green from week 0 baseline through week 12. And you see that the percentage change in Average pain was higher in the Qutenza group with a 30 percent change versus placebo group of 22 percent that was statistically significant. And this was a sustained pain relief over 12 weeks.
Now here we see a secondary endpoint which is the time to treatment response and here treatment response is defined as a greater than 30% pain reduction from baseline and you see that in the capsaicin group the time to this treatment response was a mean of 19 days whereas in the placebo group it was 72 days. And the Qutenza pain relief occurred as early as the second week.
Next slide shows another secondary endpoint which is the effect on sleep interference and whether we look at the results from baseline to week 2 to 8 or baseline to week 2 to 12 Qutenza achieved an improvement in this score that is a reduction in sleep interference or a greater reduction in sleep interference as compared to Placebo that was statistically significant.
Next slide shows yet another secondary endpoint and this is the responder rate. Here again responder is defined as patients achieving greater or equal to 30 percent reduction in pain from baseline and it's been shown and validated in prior studies by John Farrar and others at this 30 percent reduction is considered a clinically significant reduction in pain and you can see that this reduction in pain that is the responder rate over 30 percent was greater in the Qutenza group than in the placebo group at a statistically significant level.
Of course safety and tolerability are key attributes of any new medication analysis and one of the advantages of the Qutenza high concentration patch is that this is a topical that's significant or meaningful systemic absorption. And so all of the side effects that we see are local due to application site reaction as opposed to any systemic reaction, which is absent in this drug. And as you see on the table here the side effects that occurred that were greater in the Qutenza group versus control were those that one might expect from an application site reaction, including a burning sensation some local pain local erythema. And these were relatively mild and minor reactions and as you can see on the right, none of these adverse effects led to the patient requesting discontinuation of treatment or removal of the patch prematurely and there were no drug related serious adverse events.
So to conclude Qutenza as shown in this phase 3 placebo-controlled study provided statistically significant improvements in pain relief as compared to placebo in patients with painful diabetic neuropathy. And so was well tolerated, the most common treatment emergent adverse effects were application site reactions. These findings were consistent with safety observations that have been seen in prior trials in the other FDA-approved indication for Qutenza, which is post herpetic neuralgia. There were no discontinuations due to any drug related adverse event, no deaths or serious AE were reported and interestingly when one is concerned and measured sensory perception, which was done in this and several other trials. There was no deterioration in sensory perception including sharp, cold, or warm sensory perception, which is an important observation particularly as we think of the mechanism of action of Qutenza with its effects on epidermal nerve fibers. Interestingly there were even some early signal suggesting a possible improvement in sensory function following Qutenza though that needs to be pursued and validated in future studies.
Now what about some of the additional clinical benefits of Qutenza that extend beyond pain relief, quality of life. And there are quality of life measures that have shown benefit with this agent. We've talked about safety. There are no drug drug interactions because this is not a systemic agent and one can imagine that when one is using a medication that is administered by the health care provider in the clinic without any need for the patient to self-treat as they would with for example taking oral medications on a daily basis is certainly may lead to improved adherence or lease the lack of non-adherence. There is also a lower potential for misuse particularly if we think of some of the pain medications being used like opioids and no potential for addiction, again in contrast to opioids
Important safety information
- Do not dispense QUTENZA to patients for self-administration or handling. Only physicians or healthcare professionals under the close supervision of a physician are to administer and handle QUTENZA.
- Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin in healthcare providers and others. When administering QUTENZA, it is important to follow the procedures in the Important Dosage and Administration Instructions in the USPI.
- In patients treated for neuropathic pain associated with diabetic peripheral neuropathy, a careful examination of the feet should be undertaken prior to each application of QUTENZA to detect skin lesions related to underlying neuropathy or vascular insufficiency.
Warnings and Precautions
- Aerosolization of capsaicin can occur upon rapid removal of QUTENZA. Therefore, remove QUTENZA gently and slowly by rolling the adhesive side inward. Inhalation of airborne capsaicin can result in coughing or sneezing. If irritation of airways occurs, remove the affected individual from the vicinity of QUTENZA. Provide supportive medical care if shortness of breath develops.
- If skin not intended to be treated is exposed to QUTENZA, apply Cleansing Gel for one minute and wipe off with dry gauze. After the Cleansing Gel has been wiped off, wash the area with soap and water.
- Patients may experience substantial procedural pain and burning upon application and following removal of QUTENZA. Prepare to treat acute pain during and following the application procedure with local cooling (such as a cold pack) and/or appropriate analgesic medication.
- Transient increases in blood pressure may occur during and shortly after the QUTENZA treatment. Blood pressure changes were associated with treatment-related increases in pain. Monitor blood pressure and provide adequate support for treatment-related pain. Patients with unstable or poorly controlled hypertension, or a recent history of cardiovascular or cerebrovascular events, may be at an increased risk of adverse cardiovascular effects. Consider these factors prior to initiating QUTENZA treatment.
- Reductions in sensory function have been reported following administration of QUTENZA. Decreases in sensory function are generally minor and temporary. All patients with pre-existing sensory deficits should be clinically assessed for signs of sensory deterioration or loss prior to each application of QUTENZA. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of QUTENZA treatment should be reconsidered.
- In all controlled clinical trials, adverse reactions occurring in ≥5% of patients in the QUTENZA group and at an incidence at least 1% greater than in the control group were application site erythema, application site pain, and application site pruritus.
For additional information, please see the full Prescribing Information, including Patient Information.
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M-QZA-US-10-20-0018 October 2020