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Patient and Physician Perspectives on Mode of Administration of the PCSK9 Monoclonal Antibody Alirocumab, an Injectable Medication to Lower LDL-C Levels
Clinical trials of the PCSK9 inhibitor alirocumab, an every 2 week injectable monoclonal antibody, have shown significant reductions in LDL-cholesterol. However, many patients requiring lipid-lowering therapy are not experienced with self-injected medication. This study assessed patient and physician perceptions of 2 alirocumab delivery devices.
Methods
400 participants (200 physicians, 200 patients) were included from 6 countries. Physicians (99 primary care physicians [PCPs]; 101 specialists) had mean practice experience of 17.8 years and an average of 797 hypercholesterolemic patients. Participating patients had LDL-C levels above their goal and at least one of the following: familial hypercholesterolemia, statin intolerance, high cardiovascular risk, and/or diabetes. Mean patient age was 58.5 years, 51% were female, and 25.5% had injectable medication experience. Following device instruction and demonstration, participants tested either a pre-filled pen or pre-filled syringe, using both 75 and 150 mg doses of single-blinded placebo into a prosthetic pad. Data were collected by self-administered questionnaire.
Findings
Participant acceptance of both devices was positive, with 83-100% agreeing with ease-of-use statements. After testing, physicians estimated that 66% (pen) and 58% (syringe) of their patients would be willing to self-inject using the device (relative increases from pre-testing of 22% and 16%, respectively; both P<0.05). Specialist estimates were higher than PCP estimates: for the pen, 60% versus 47% (pre-testing), respectively, and 72% versus 61% (post-testing); for the syringe, 57% versus 43% (pre-testing), 63% versus 54% (post-testing; all P<0.05, specialist vs PCP). After testing, 72% (pen) and 63% (syringe) of patient-participants were very willing to self-inject (relative increases from pre-testing of 26% [P<0.05] and 11%, respectively); 96% (pen) and 93% (syringe) were either very willing or somewhat willing to self-inject. The proportion of patients aged <60 years who were very willing to self-inject with either device was numerically (but not statistically) higher compared with those ≥60 years. Initially, patients with injectable medication experience were generally more willing to use the pen than injection-naive patients; after testing there was no difference between groups. No significant differences were observed in responses to the 2 different doses.
Implications
Responses from physicians and patients to pre-filled pen and syringe devices were positive. Devices were considered easy to operate, with most patients willing to use and accept self-injection. Patient willingness to self-inject increased after demonstration and testing. Results suggest that, in clinical practice, alirocumab administration by either pre-filled pen or syringe would not deter most physicians from prescribing or most patients from self-administering.
ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.
Gitt AK, Ambegaonkar B, Brudi P, et al. Low LDL-cholesterol target achievement in statin-treated patients in clinical practice in China and Europe: results of the Dyslipidemia International Study (DYSIS). J Am Coll Cardiol. 2015;65(10_S):A1482.
Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status.
Residual dyslipidemia among United States adults treated with lipid modifying therapy (data from National Health and Nutrition Examination Survey 2009-2010).
Alirocumab is a fully human monoclonal antibody that binds to and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that is involved in regulating circulating levels of LDL-C.
Clinical trials of alirocumab, administered as either monotherapy or with background statin therapy (with and without other lipid-lowering therapies), have shown the therapeutic potential to reduce LDL-C levels, with significant reductions from baseline after 24 weeks of treatment ranging from 47% to 61%.
Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.
Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.
Alirocumab is administered via subcutaneous injection. Two delivery devices have been used in alirocumab Phase III clinical trials, a prefilled syringe
Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.
Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.
However, many patients requiring lipid-lowering therapy will not have experience with injectable medications and, similarly, physicians will have little experience prescribing injectable lipid-lowering drugs. The only such agent currently available commercially is mipomersen, an antisense oligonucleotide targeting apolipoprotein B. Mipomersen is licensed in the United States only for the treatment of homozygous familial hypercholesterolemia (FH), which affects an estimated 1 in 1 million individuals in most parts of the world.
It is therefore important to understand how patients and physicians perceive alirocumab administration devices. The present study was designed to assess patient and physician perceptions of the ease of use and acceptance of those devices.
Patients and Methods
Participants
A total of 400 participants (200 physicians and 200 patients) were included from 6 countries: 100 physicians and 100 patients from the United States, and 20 of each from 5 European countries (France, the United Kingdom, Spain, Germany, and Italy) (Figure 1). Of the physicians, 99 were primary care physicians (PCPs), and 101 were specialists (cardiologists, endocrinologists, diabetologists, lipidologists, nephrologists [Germany only], and chemical pathologists [United Kingdom only]) (Table I). Patients enrolled were not at their LDL-C goal (as set by their physician) and had at least 1 of the following: FH, statin intolerance, high CV risk, and/or diabetes.
Figure 1Study structure and flow. *Participants tested the device by injecting into a prosthetic pad; the placebo device was developed to mimic the consistency and viscosity of the active dose. EU = European Union; UK = United Kingdom.
Patient categories were defined as follows. All patient participants were diagnosed as having a high LDL-C level that was not at goal, in addition to 1 of the following factors. High CV risk: diagnosed with, or experienced, at least 1 CV risk factor (from: unstable angina; heart attack/myocardial infarction; stroke/transient ischemic attack; peripheral arterial disease; bypass surgery; percutaneous coronary intervention [angioplasty] with or without stent; chronic heart disease, or chronic kidney disease) OR diagnosed with diabetes and with at least 2 additional CV risk factors (from: hypertension/high blood pressure; retinopathy, neuropathy; microalbubinuria [urine albumin]; family history of chronic heart disease); not diagnosed with FH or statin intolerant. Diabetic: diagnosed with diabetes and <2 additional CV risk factors; not diagnosed with FH or statin intolerant. Statin intolerant: discontinued ≥2 statins due to muscle-related adverse effects; not currently receiving high-dose statins; not diagnosed with FH. Patients receiving low-dose statins could still be considered as statin-intolerant if they had discontinued higher dose statins previously. “High-dose statins” were defined as simvastatin 40 to 80 mg, pravastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, lovastatin 60 mg, fluvastatin 80 mg, or pitavastatin 4 mg. All lower doses were considered as “low-dose statins.” FH: diagnosed with FH and has a family history of cardiac death before 50 years of age; diagnosed with high cholesterol at age ≤50 years; questions on family history and high cholesterol were posed to validate the patient-reported diagnosis of FH.
Patient categories were defined as follows. All patient participants were diagnosed as having a high LDL-C level that was not at goal, in addition to 1 of the following factors.High CV risk: diagnosed with, or experienced, at least 1 CV risk factor (from: unstable angina; heart attack/myocardial infarction; stroke/transient ischemic attack; peripheral arterial disease; bypass surgery; percutaneous coronary intervention [angioplasty] with or without stent; chronic heart disease, or chronic kidney disease) OR diagnosed with diabetes and with at least 2 additional CV risk factors (from: hypertension/high blood pressure; retinopathy, neuropathy; microalbubinuria [urine albumin]; family history of chronic heart disease); not diagnosed with FH or statin intolerant.Diabetic: diagnosed with diabetes and <2 additional CV risk factors; not diagnosed with FH or statin intolerant.Statin intolerant: discontinued ≥2 statins due to muscle-related adverse effects; not currently receiving high-dose statins; not diagnosed with FH. Patients receiving low-dose statins could still be considered as statin-intolerant if they had discontinued higher dose statins previously. “High-dose statins” were defined as simvastatin 40 to 80 mg, pravastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, lovastatin 60 mg, fluvastatin 80 mg, or pitavastatin 4 mg. All lower doses were considered as “low-dose statins.”FH: diagnosed with FH and has a family history of cardiac death before 50 years of age; diagnosed with high cholesterol at age ≤50 years; questions on family history and high cholesterol were posed to validate the patient-reported diagnosis of FH.
The study was conducted in December 2014. The appropriate specific market research ethics guidelines were followed (eg, European Pharmaceutical Market Research Association, British Healthcare Business Intelligence Association). Prior consent was sought with participants before starting the research. This consent included permission for audio and video recording (and storage) and agreement to be watched live with study sponsors in attendance.
Data Collection
Data were collected via self-administered questionnaires in a structured interview. Participant assignment and study flow are shown in Figure 1. The interview was conducted in a central location in each country and involved a 30-minute self-completion exercise. A moderator was present for assistance, although the interview was designed to ensure the moderator had no involvement in data collection. The identity of alirocumab was blinded, with an unbranded name (“Voypaz”) used instead.
After introduction to the drug, participants (physicians or patients) were asked about willingness to prescribe or self-inject before using the device (introductory drug details and specific questions are shown in the Supplemental Materials [see the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008]). Participants were randomly assigned to interact with either the pen or the syringe. After device training (which involved instruction and demonstration with a prosthetic pad), participants tested each of 2 doses (75 and 150 mg) by pad injection. The actual substance injected was a placebo developed to mimic the viscosity of alirocumab. Both devices used a 27-G thin-walled needle, although this detail was not shared with participants. After testing, participants completed a questionnaire for each dose consisting of a list of statements about device operation and ease of use. Participants indicated whether they agreed or disagreed with each statement. Statements were presented in a random order; some statements were specific to patients (and not shown to physicians) and some were specific to the pen (and were not shown to participants using the syringe).
After testing the devices and responding to the ease-of-use statements, participants were asked again about their willingness to prescribe or self-inject (specific questions are shown in the Supplemental Materials [available in the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008]). Physicians were asked to estimate the percentage of their patients (with uncontrolled LDL-C) who would be willing to self-inject. Patients indicated their level of willingness to self-inject from 5 options (very willing, somewhat willing, neither willing nor unwilling, somewhat unwilling, and very unwilling).
An “Instructions for Use” document (including storage, preparation, and injection instructions for the device) was provided to participants, based on the intended actual alirocumab device packaging. Moderators demonstrated how to use the device and read from a script to describe the process (the script was based on the “Instructions for Use” product insert) to ensure consistency. The pen and syringe devices had equal exposure across patients and physicians. The order in which doses were seen was rotated to avoid bias (ie, 75 and 150 mg were seen first an equal number of times).
The prosthetic pad was a multilayered soft tissue pad used to train and allow patients to practice subcutaneous injection techniques. The pad was flexible with multiple tissue layers representing the epidermis, dermis, fat, and muscle layers allowing patients to pinch the “skin” and inject. The pad was equipped with a strap which allowed the moderator to demonstrate the injection on his or her thigh; respondents were allowed to inject on their thigh or stomach or on the table top. No physician or patient received an actual injection. Injection training via prosthetic pad has previously been shown to increase patient confidence in self-administering injections.
The sample was constructed so that significance testing could be conducted at each level of design. To have an adequate number for significance testing, the cell size could not fall below 20. The sample size was determined to be n = 400 (with 200 physicians/patients [200 testing the pen/syringe, and 200 testing the 75-/150-mg doses]). Furthermore, in addition to the physician/patient, pen/syringe, and 75-/150-mg dose categories, there was a geography category, with 200 respondents in the United States and 200 in the European Union. Of the 200 respondents in the European Union, there were 40 in each of the 5 countries (20 evaluating the pen, and 20 evaluating the syringe).
P values were calculated by using SPSS software, version 21 (IBM SPSS Statistics, IBM Corporation, Armonk, New York). A significance level of 0.05 and the Bonferroni correction were used for all tests. Pairwise comparisons of proportions were performed by using a z test when the test variable was categorical, and pairwise comparisons of means were performed by using a t test when the variable was scale. Because no significant differences were found between the 2 doses tested, results for the 2 doses were pooled.
Results
Baseline Characteristics of Participants
Physicians had mean practice experience of 17.8 years since residency and were managing an average of 797 patients with hypercholesterolemia, with 77% of them receiving lipid-lowering therapy. None of the physicians had previously been involved in alirocumab trials.
The mean age of patients was 58.5 years; 51% were female, and 25.5% had previous injectable medication experience (any medication). Eighty-four percent were white, 12.5% were black/African American, 2% were Latin American/Hispanic, and the remaining 1.5% were either Asian/Pacific Islander, Native American/Indian or Other (0.5% each). The majority of patients (88%) were receiving a statin. Patient LDL-C levels and details of previous injectable medications were not recorded. Characteristics of the patients assigned to the prefilled pen or syringe group were similar (eg, mean age 58 years [pen] and 59 years [syringe]; 52% [pen] and 50% [syringe] were female; and 25% [pen] and 26% [syringe] had previous injectable medication experience) (Supplemental Table I [available in the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008]). Characteristics of patients in the United States and European Union were also similar (Supplemental Table II [available in the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008]).
Results for Physicians
Physician acceptance of both devices was positive, with 83% to 100% agreeing with statements regarding device operation and ease of use (see Supplemental Figure 1 in the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008). Example statements included “The injection is easy for patients to learn,” and “I would recommend the Voypaz pen to my patients.”
After instruction and testing of devices, physicians considered that 66% (pen) and 58% (syringe) of their patients would be willing to use self-injectable alirocumab (relative increases from before testing of 22% and 16%, respectively; both P < 0.05) (Figure 2A). Physician estimates after testing were higher with the pen (66%) than with the syringe (58%; P < 0.05). Specialist estimates were higher than PCP estimates: for the pen, estimates were 60% versus 47% (before testing), respectively, and 72% versus 61% (after testing); for the syringe, estimates were 57% versus 43% (before testing) and 63% versus 54% (after testing) (all, P < 0.05 specialist vs PCP) (Figures 2B and C). There were no significant differences between responses of physicians based in the United States versus the European Union (Table II).
Figure 2(A) Physician estimates of patient willingness to self-inject (pre-testing and post-testing) and primary care physicians (PCPs) versus specialists for (B) the pen and (C) syringe. *P < 0.05, after testing versus before testing. In panel A, estimates were higher after testing with the pen (66%) than with the syringe (58%; P < 0.05); estimates with the pen and syringe were not significantly different for the other comparisons.
Table IIPhysician responses according to region (United States or European Union): percentage of patients whom physicians estimate would be willing to self-inject.
Patient acceptance of both devices was also positive, with 86% to 100% agreeing with statements regarding device operation and ease of use (see Supplemental Figure 2 in the online version at http://dx.doi.org/10.1016/j.clinthera.2015.07.008). Example statements included “The pen is convenient to use, which can make it easy for you to stay with your treatment,” and “Visual and audio cues confirm when the injection begins and the injection is completed.”
After instruction and testing, 72% (pen) and 63% (syringe) of participating patients indicated that they were very willing to self-inject the drug if their physician recommended it to them (relative increases from before testing of 26% [P < 0.05] and 11%, respectively) (Figure 3A). More patients were very willing to self-inject after testing with the pen (72%) than with the syringe (63%; P < 0.05).
Figure 3Patients reporting they would be “very willing” to self-inject pre-testing and post-testing, according to: (A) device; (B) for those aged ≥60 years versus those aged <60 years; and (C) according to level of injection experience. *P < 0.05, after testing versus before testing. In panel A, more patients were very willing to use the devices after testing with the pen (72%) than with the syringe (63%; P < 0.05); results with the pen and syringe were not significantly different for the other comparisons.
Most patients stated they were at least somewhat willing to self-inject with both devices (Table III). After testing, 96% (pen) and 93% (syringe) of patients indicated that they were either “very willing” or “somewhat willing” to self-inject (relative increases from before testing of 6.7% and 4.5%, respectively; both nonsignificant). The majority of patients indicated that they would be confident in self-injecting on their own at home (74% with the pen, 66% with the syringe; patients were only asked about injecting at home after they had tested the devices).
Table IIIPatient willingness to self-inject for overall participant population.
The proportion of patients aged <60 years who were very willing to self-inject with either the pen or syringe was numerically but not statistically different from corresponding figures for patients aged ≥60 years (Figure 3B). Initially, patients with injectable medication experience were generally more willing to use the pen than injection-naive patients; after instruction and testing, there was no difference between groups (Figure 3C). Among female subjects who tested the pen, 52% indicated before testing that they were very willing to self-inject; this value increased to 69% after testing (P < 0.05). There were numerical but not statistically significant differences in corresponding figures for male subjects who tested the pen or either sex who tested the syringe (Table IV). Willingness to self-inject increased for both devices across all patient CV risk categories, except for FH (100% were “very willing” both pre-testing and post-testing) (Table V). No significant differences were observed in participant responses to the 2 different doses.
Table IVMale and female patients reporting they would be “very willing” to self-inject pre-testing and post-testing, according to device.
The majority of patients in both the United States and the European Union were very willing to self-inject after testing the devices, although a greater proportion of US patients (82%) stated that they would be very willing to self-inject with the pen after testing compared with those from the European Union (62%; P < 0.05) (Table VI). The majority of patients from the European Union stated they were at least somewhat willing to self-inject with the pen. However, there were no regional differences for the syringe.
Table VIPatient willingness to self-inject according to region.
The main findings of this research were that physician and patient acceptance of alirocumab injection devices was positive. Although nearly 75% of patients had no previous experience with injectable medication, the devices were considered easy to use, with most patients willing to use and accept self-injection after instruction and testing. Both devices scored well for usability, although willingness to self-inject or prescribe was higher with the pen than with the syringe. Importantly, patients were more willing to self-inject after demonstration and testing of the devices (as were physician estimates of the percentage of patients who would be willing to self-inject). This finding indicates that training would be important to increase patient acceptance of the alirocumab administration devices.
Among the physician participants, willingness to prescribe a lipid-lowering medication using either of the devices was higher among specialists compared with PCPs. Among patient participants, there were numerical (although not statistically significant) differences in the proportion of patients who were “very willing” to self-inject, suggesting that the devices were more acceptable to patients aged <60 years compared with those aged ≥60 years. There were no significant differences between physician estimates of patient willingness and patient-reported willingness to self-inject. Acceptance of both devices was positive across patient CV risk categories (eg, high CV risk, statin intolerance, diabetes, FH). Of the patients with FH, 100% gave “very willing” responses (although the group included only 3 patients). It could be speculated that this group of patients (who have genetically elevated LDL-C levels and are at lifelong increased risk for CV disease) are more willing to accept lipid-lowering medication by injection. This study included participants from the United States and 5 countries from the European Union. Responses from physicians based in the United States and from the European Union were highly similar. A larger proportion of patients from the United States compared with those from the European Union stated after testing that they would be very willing to use the pen; however, there was no difference for the syringe.
Results from the present study indicate that the majority of patients would be willing to use either of the alirocumab injection devices. However, it is important to understand patient acceptance of actual injections of alirocumab given to them in practice. A limitation of this study was that patients did not perform injections on themselves and did not use the active drug. A questionnaire assessing patient acceptance of actual self-administered alirocumab injections has been developed based on interviews with patients involved in the Phase III clinical trials of alirocumab. Preliminary results suggest high patient acceptance of alirocumab injections, with patients finding both the prefilled pen and syringe easy to use.
In addition, a device questionnaire was given to patients enrolled in the ODYSSEY CHOICE II trial (ClinicalTrials.gov: NCT02023879). Data from completed trials also indicate high patient acceptance of alirocumab injections. Adherence to injections (the percentage of days that patients received injections according to the dosing schedule) was reported for 2 studies: 98% used the prefilled syringe in ODYSSEY LONG TERM (over 78 weeks’ duration),
Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.
Furthermore, in the ODYSSEY CHOICE II Phase III study (ClinicalTrials.gov identifier: NCT02023879; manuscript in preparation), the overall experience in performing self-injection at home was rated as 6 or 7 (7 = extremely satisfied) by 93% of patients. In all the Phase III trials, patients could choose to self-inject at home or have a caregiver administer the drug. In the ODYSSEY MONO trial, 92% of patients who were allocated to receive alirocumab opted to self-inject at home (data not reported for other completed trials).
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.
Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies.
Kastelein JJP, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 [in press].
Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial.
). Patients with diabetes were not specifically recruited although they were well represented in the ODYSSEY Phase III clinical trial program.
Conclusions
Acceptance of the alirocumab prefilled pen and syringe devices was positive. The devices were considered easy to operate, with most patients willing to use and accept self-injection, particularly after training. Results suggest that, in clinical practice, the prefilled pen or syringe devices would not deter most physicians from prescribing and would not deter most patients from self-administering the drug.
Conflicts of Interest
Dr. Roth is employed by a company that has received research funds and fees for consulting from Regeneron, Sanofi, and Amgen, and for speaker’s bureau from Merck and AstraZeneca, and advisory boards for Sanofi, Regeneron, Merck, and AstraZeneca; Dr. Bujas-Bobanovic is a stockholder and employee of Sanofi; Dr. Louie is a stockholder and employee of Regeneron; and Dr. Cariou has received research funds from Sanofi and fees from consulting and/or advisory boards from Amgen, AstraZeneca, DebioPharm, Janssen, Eli Lilly, Genfit, Novo-Nordisk, Regeneron, and Sanofi. The authors have indicated that they have no other conflicts of interest regarding the content of this article.
Acknowledgments
This study was conducted, and the data analyzed by, Blueprint Partnership Ltd. and was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing was provided by Rob Campbell of Prime Medica Ltd., funded by Sanofi and Regeneron Pharmaceuticals, Inc.
The authors thank all participants in this study and also the following persons from the sponsors for their contributions to data collection and analysis, assistance with statistical analysis, or critical review of the manuscript: Regeneron Pharmaceuticals, Inc, William J. Sasiela, PhD, and Carol Hudson, BPharm; Sanofi, Jay Edelberg, MD, PhD, Veronica Lee, MD, and Michael Howard, MBA; and Blueprint Partnership, Joshua Roche, BSc.
All authors provided interpretation of the data and critical revisions to the manuscript, and have approved the final article.
Supplemental Figure 1Responses to statements regarding device operation and ease of use from physicians for (A) the prefilled pen and (B) the prefilled syringe (% agreement).
Supplemental Figure 2Responses to statements regarding device operation and ease of use from patients for (A) the prefilled pen and (B) the prefilled syringe (% agreement).
Today you will be looking at an injection device for a potential new medication for high cholesterol, which will be referred to as Voypaz. Voypaz is an approved, unbranded name which you will see in this research only. This is a working name for product testing purposes; this is not the real product name. You will be given an opportunity to look at the device, use the device, and then review statements which relate to the device.
You will be looking at two doses of the device today.
Before you look at the device, here is a brief summary about the product with which the device will be used. Note that the product itself is not the focus of our discussion, but we’ll go through the information to help you better understand the statements you will see.
•
Voypaz is a new prescription medication currently under development for patients who need additional help lowering their high cholesterol.
•
In clinical trials, Voypaz has been shown to lower ‘bad’ cholesterol (LDL) by an additional 45–61% on top of your current statin therapy, and by 45–47% when statins cannot be taken due to side effects.
•
There have been no serious safety issues observed for Voypaz and significantly fewer muscle pain or liver side effects.
The most frequent side effects seen in clinical trials have been minor injection-site reactions such as redness or irritation. Voypaz can be used safely with statins and other commonly used medications for high blood pressure, stroke prevention, kidney disease, and diabetes
*Compared with statins
•
Voypaz is a medication that you self-inject into your skin with a ready-to-use, single-use, disposable injection device once every 2 weeks. The injection can be given by a family caregiver or friend if desired
•
There are two doses available for Voypaz, 75 mg and 150 mg, and your doctor will determine which one is right for you. Regardless of dose, both are delivered with the same amount of liquid (1 mL) with the same device.
•
Voypaz is kept in a refrigerator at a cold temperature and brought to room temperature before using (which takes about 30–40 minutes)
If you have any questions or uncertainties about the product information, check with the moderator before continuing.
Questions Asked To Physicians Before and After Testing The Devices
Before Testing
Thinking of only the patients with uncontrolled LDL-C and a high CV risk profile whom you would consider prescribing Voypaz to, what percentage do you think would be willing to self-inject Voypaz? (i.e. 100% is all of the patients who are suitable and you consider prescribing Voypaz to)
After Testing
Now that you have had a chance to read the instructions and try the device…
Thinking of only the patients with uncontrolled LDL-C and a high CV risk profile whom you would consider prescribing Voypaz to, what percentage do you think would be willing to self-inject Voypaz? (i.e. 100% is all of the patients who are suitable and you consider prescribing Voypaz to)______% (fill in from 0% to 100%)
Questions Asked To Patients Before and After Testing The Devices
Before Testing
After reading this information about Voypaz, how willing would you be to self-inject Voypaz if it was recommended to you by your doctor?
Select answer which best applies
□
I would be very willing to self-inject Voypaz if my doctor recommended it to me
□
I would be somewhat willing to self-inject Voypaz if my doctor recommended it to me
□
I would be neither willing nor unwilling to self-inject Voypaz if my doctor recommended it to me
□
I would be somewhat unwilling to self-inject Voypaz if my doctor recommended it to me
□
I would be very unwilling to self-inject Voypaz if my doctor recommended it to me
After Testing
Now that you have had a chance to read the instructions and try the device, how willing would you be to self-inject with Voypaz to treat your high cholesterol, if your doctor recommended this medication to you?
Select answer which best applies
□
I would be very willing to self-inject Voypaz if my doctor recommended it to me
□
I would be somewhat willing to self-inject Voypaz if my doctor recommended it to me
□
I would be neither willing nor unwilling to self-inject Voypaz if my doctor recommended it to me
□
I would be somewhat unwilling to self-inject Voypaz if my doctor recommended it to me
□
I would be very unwilling to self-inject Voypaz if my doctor recommended it to me
References
Baigent C.
Blackwell L.
Emberson J.
et al.
Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.
Gitt AK, Ambegaonkar B, Brudi P, et al. Low LDL-cholesterol target achievement in statin-treated patients in clinical practice in China and Europe: results of the Dyslipidemia International Study (DYSIS). J Am Coll Cardiol. 2015;65(10_S):A1482.
Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status.
Residual dyslipidemia among United States adults treated with lipid modifying therapy (data from National Health and Nutrition Examination Survey 2009-2010).
Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.
Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.
Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies.
Kastelein JJP, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 [in press].
Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial.
Patient categories were defined as follows. All patient participants were diagnosed as having a high LDL-C level that was not at goal, in addition to 1 of the following factors.High CV risk: diagnosed with, or experienced, at least 1 CV risk factor (from: unstable angina; heart attack/myocardial infarction; stroke/transient ischemic attack; peripheral arterial disease; bypass surgery; percutaneous coronary intervention [angioplasty] with or without stent; chronic heart disease, or chronic kidney disease) OR diagnosed with diabetes and with at least 2 additional CV risk factors (from: hypertension/high blood pressure; retinopathy, neuropathy; microalbubinuria [urine albumin]; family history of chronic heart disease); not diagnosed with FH or statin intolerant.Diabetic: diagnosed with diabetes and <2 additional CV risk factors; not diagnosed with FH or statin intolerant.Statin intolerant: discontinued ≥2 statins due to muscle-related adverse effects; not currently receiving high-dose statins; not diagnosed with FH. Patients receiving low-dose statins could still be considered as statin-intolerant if they had discontinued higher dose statins previously. “High-dose statins” were defined as simvastatin 40 to 80 mg, pravastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, lovastatin 60 mg, fluvastatin 80 mg, or pitavastatin 4 mg. All lower doses were considered as “low-dose statins.”FH: diagnosed with FH and has a family history of cardiac death before 50 years of age; diagnosed with high cholesterol at age ≤50 years; questions on family history and high cholesterol were posed to validate the patient-reported diagnosis of FH.
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