REIMAGINE EFFECTIVE PREVENTION
With 125 patients, HELP was one of the largest studies in HAE prevention with the longest active treatment duration1-5
TAKHZYRO is clinically proven to help prevent HAE attacks with every-2-weeks dosing that takes ≤1 minute to administer—patients experienced long-term freedom from attacks for an average of 14.8 (SD=12.4) months1,2*†‡
*In clinical studies, the majority of patients self-administered TAKHZYRO within 10 to 60 seconds.1 †Evaluated in a 6.5-month study and a 2.5-year open-label extension (OLE) study.1,2 ‡Mean duration of the attack-free period in the OLE study was 14.8 (SD=12.4) months (N=209).2 SD=standard deviation.
TAKHZYRO was studied in a range of patients with HAE type I or II1,2
- 70% Female6
- 30% Male6
- 12 to 73 Years of Age7
of active treatment
- (26 weeks)1,6*
with long-term
preventive therapy1
- 48% were on C1-INH alone6
- 3.2% were on oral therapy6†
- 4.8% were on both6
44% of patients at baseline in HELP had not previously received long-term preventive therapy.6
*One month was defined as 28 days in the pivotal trial.6 †Androgens or antifibrinolytics.6
Help Study Design
*Long-term preventive therapy washout was only for patients ≥18 years of age.7
†Run-in period could be shortened if the patient experienced ≥3 HAE attacks before completion of the 4 weeks, and the period could be extended to 8 weeks if the patient did not experience any attacks during the 4 weeks. During the 8 weeks, the patient needed to have ≥2 attacks to proceed to enrollment and randomization.6
‡Treatments were administered as 2 separate 1-mL injections in the upper arm every 2 weeks to maintain the blind.6
§One month was defined as 28 days in the trial.6
The pivotal trial was a multicenter, double-blind, parallel group, placebo-controlled, dose-ranging study, which assessed the safety and efficacy of TAKHZYRO in 125 patients with HAE type I or II (≥12 years of age). Patients were randomized to receive TAKHZYRO 150 mg every 4 weeks (n=28), TAKHZYRO 300 mg every 4 weeks (n=29), TAKHZYRO 300 mg every 2 weeks (n=27), or placebo (n=41) for 26 weeks (6.5 months, where 1 month was defined as 28 days). Prior to randomization, patients ≥18 years of age were required to complete a ≥2-week long-term prophylaxis washout period. All patients then entered a 4-week run-in period to determine the baseline HAE attack rate. Patients with ≥1 investigator-confirmed HAE attack during the run-in period were eligible for study enrollment and randomization. The primary efficacy endpoint was the rate of investigator–confirmed attacks during the treatment period (time frame: from Day 0 to Day 182).1,6
Rediscover Effective HAE Attack Prevention
Significant reduction in mean attack rate* vs placebo at 6.5 months in the HELP study1,6
IN ATTACKS
- TAKHZYRO 300 mg every 4 weeks resulted in a 73% reduction in attacks vs placebo (Adjusted P<0.001)1†
- Mean monthly attack rate at baseline (during run-in period): 3.52 for TAKHZYRO every 2 weeks (n=27); 3.71 for TAKHZYRO every 4 weeks (n=29); 4.02 for placebo (n=41)6
- Mean monthly attack rate (during treatment): 0.26 for TAKHZYRO every 2 weeks; 0.53 for TAKHZYRO every 4 weeks; 1.97 for placebo1
All data presented are for TAKHZYRO 300 mg every 2 weeks unless otherwise indicated.1
*Mean monthly attack rate: number of attacks/4 weeks.1
†Adjusted P-values for multiple testing.1
SELECT IMPORTANT SAFETY INFORMATION
Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment.
Significant reduction in moderate and severe attacks and attacks requiring acute treatment vs placebo at 6.5 months1,6
‡Adjusted P-values for multiple testing.1
Freedom from HAE attacks in the HELP study
All data presented are for TAKHZYRO 300 mg every 2 weeks unless otherwise indicated.
The Right Patient for TAKHZYRO
Dive in and learn more about who might be the right patient for TAKHZYRO. By examining the characteristics of their own HAE patients, as well as looking at the HAE community at large, 2 HAE experts will discuss what makes a patient right for TAKHZYRO.
View Transcript
Dr Michael Manning: I was just thinking about how far we've come for patients with HAE in the last 15 years. A few weeks ago, one of my patients who is on preventive therapy went hiking with his father. This is something he used to choose to avoid in case he would have an HAE attack.
Dr Douglas Lotz: I agree. Preventive therapy has been impactful for many of my patients as well.
Dr Michael Manning: I found that my patients with HAE who really know their triggers and go out of their way to avoid them could likely benefit from preventive treatment, including those who recognize stress is a trigger. When job or family pressures come into play, the last thing they want is an HAE attack added on.
Dr Douglas Lotz: It's why it's so important to have the right conversations in order to uncover their specific situations and to address their unique goals. I wouldn't want my patients avoiding things out of concern for their next attack.
Dr Michael Manning: You know, I'll ask them things like, "Are there activities you're missing out on? Do you think about your next attack?" Sometimes, a patient has an attack only once in six months, but it may still cause disruption. I don't want my patients missing events. Even for a patient with very few attacks per month, if they're anticipating having one, I recommend they consider a preventive medication like TAKHZYRO.
Dr Douglas Lotz: You hit on a really good point there. No matter what a patient's HAE attack frequency is, the unpredictability of those attacks can be challenging. Patients may ask themselves, "When is my next attack going to happen? Is it going to be life-threatening?"
Dr Michael Manning: I've also had patients who didn't realize their symptoms were HAE attacks. One time, the wife of one of my patients mentioned that her husband was having stomach pains several times a month. He didn't realize it was his HAE attacks until I put him on preventive treatment and his attacks became less frequent. But I recognize these are his experiences and every patient's experience is different.
Dr Douglas Lotz: Mike, what do you do to anticipate situations like the one you just mentioned?
Dr Michael Manning: You know, Doug, I tend to ask patients a lot of questions such as, "Are you having any recurring issues that may seem mild, but pop up now and then?" I ask about areas of the body where HAE attacks may typically occur even if the patient hasn’t experienced swelling at that location.
Dr Douglas Lotz: That's a really good point. One additional consideration I have when looking at treatment options for patients is the route of administration. TAKHZYRO is a subcutaneous injection. How do you identify which patients are right for TAKHZYRO? Do you consider disease severity?
Dr Michael Manning: You know, I don't label a patient with HAE as mild, moderate, or severe, because if you label a patient as mild, what does that do? That sets you up for complacency. Any patient with HAE can have a mild, moderate, or severe attack. And HAE symptoms can change over time. It depends on how it's affecting that person.
Dr Douglas Lotz: Right. We don't have mild, moderate, or severe HAE. And I'll fight tooth and nail to never have a metric like that because we can't ever predict that the next HAE attack will be like the last one.
Dr Michael Manning: Agreed. Using terms like mild or less severe to describe HAE can be misleading. The disease is potentially life-threatening for all HAE patients.
Dr Douglas Lotz: From my point of view, the ideal patient for TAKHZYRO is really any patient who has HAE. It's for those who want to move away from infusions and for those who don't have the time or desire to treat themselves several times a week. Most of my patients, if they're six years of age or older, and have been well controlled for more than six months, meaning attack free, prefer the flexibility and option of dosing every four weeks. Of course, I always discuss with my patients the potential risks of TAKHZYRO, including the most common side effects.
Dr Michael Manning: That pediatric indication for children as young as two years of age gives us the possibility to help younger patients prevent HAE attacks.
Dr Douglas Lotz: Yes, it is great that younger patients won't have to wait to begin preventive therapy.
Dr Michael Manning: Thanks, Doug, for sharing your experiences with me.
Dr Douglas Lotz: Thank you, Mike. It's great seeing you again.
Dr Michael Manning: Great seeing you too. Thanks for joining me.
Dr Douglas Lotz: Oh, thank you.
Dr Michael Manning: Thank you so much.
Dr Douglas Lotz: Great.
Dr Michael Manning: Yeah.
Narrator: TAKHZYRO (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients ≥2 years of age.
Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment.
Adverse Reactions: The most commonly observed adverse reactions (≥10%) associated with TAKHZYRO were injection site reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory infection; headache; rash; dizziness; diarrhea; and myalgia. Less common adverse reactions observed included elevated levels of transaminases; one patient discontinued the trial for elevated transaminases.
Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients <2 years of age have not been established.
No data are available on TAKHZYRO in pregnant women. No data are available on the presence of lanadelumab in human milk or its effects on breastfed infants or milk production.
To report SUSPECTED ADVERSE REACTIONS, contact Dyax Corp., a Takeda company, at 1-877-TAKEDA-7 (1-877-825-3327), or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information at TAKHZYRO.com/hcp.
Who is the right patient for TAKHZYRO?
Hear from a patient who started TAKHZYRO after learning that their frequent HAE attacks were potentially preventable.1
SEE CASE STUDY
Explore safety profile
See safety information established in the clinical trials.
SEE SAFETY PROFILEAbout 97% of patients in the HELP study enrolled in the 2.5-year extension study2
TAKHZYRO is clinically proven to help prevent HAE attacks with every-2-weeks dosing that takes ≤1 minute to administer—patients experienced long-term freedom from attacks for an average of 14.8 (SD=12.4) months1,2*†‡
*In clinical studies, the majority of patients self-administered TAKHZYRO within 10 to 60 seconds.1† †Evaluated in a 6.5-month study and a 2.5-year open-label extension (OLE) study.1,2 ‡Mean duration of the attack-free period in the OLE study was 14.8 (SD=12.4) months (N=209).2 SD=standard deviation.
TAKHZYRO was studied in a range of patients with HAE type I or II1,2
- 109 rollover patients, which represents about 97% of patients in the pivotal trial2
- 103 nonrollover patients2
- 81.6% of patients completed the study or enrolled in commercial product2
of active treatment2
- Patients were given TAKHZYRO 300 mg every 2 weeks for a mean duration of 29.6 (SD=8.2) months2
with long-term
preventive therapy2
- 50% were on C1-INH alone2
- 6.1% were on oral therapy2*
- 3.3% were on both2
MONTH at baseline2
- 39% had ≥3 Attacks/Month at baseline2
41% of patients at baseline in HELP OLE had not previously received long-term preventive therapy2
HELP Open-label Extension Study
The open-label extension study evaluated the safety and efficacy of TAKHZYRO for up to 2.5 years in patients with HAE type 1 or type II (≥12 years of age). It included patients from the pivotal trial (rollover n=109) and additional patients (nonrollover n=103). In the long-term study, 212 patients received TAKHZYRO 300 mg every 2 weeks for a mean duration of 29.6 (SD=8.2) months. Most patients (81.6%) completed the study or enrolled in commercial product. For rollover patients, the HELP study baseline attack rate (4-week run-in period) was used as the baseline. For nonrollover patients, baseline was defined as the number of investigator-confirmed attacks reported in the last 3 months. Rollover patients, regardless of randomization group in the pivotal trial, received a single dose of TAKHZYRO 300 mg at study entry and were followed until the first HAE attack occurred. After the first HAE attack, all rollover patients received open-label treatment with TAKHZYRO 300 mg every 2 weeks. Nonrollover patients received open-label treatment with TAKHZYRO 300 mg starting on Day 0 and continued to receive TAKHZYRO every 2 weeks throughout the duration of the treatment period. The long-term safety of TAKHZYRO was the primary endpoint in the study.2
The open-label extension study evaluated the safety and efficacy of TAKHZYRO for up to 2.5 years in patients with HAE type 1 or type II (≥12 years of age). It included patients from the pivotal trial (rollover n=109) and additional patients (nonrollover n=103). In the long-term study, 212 patients received TAKHZYRO 300 mg every 2 weeks for a mean duration of 29.6 (SD=8.2) months. Most patients (81.6%) completed the study or enrolled in commercial product. For rollover patients, the HELP study baseline attack rate (4-week run-in period) was used as the baseline. For nonrollover patients, baseline was defined as the number of investigator-confirmed attacks reported in the last 3 months. Rollover patients, regardless of randomization group in the pivotal trial, received a single dose of TAKHZYRO 300 mg at study entry and were followed until the first HAE attack occurred. After the first HAE attack, all rollover patients received open-label treatment with TAKHZYRO 300 mg every 2 weeks. Nonrollover patients received open-label treatment with TAKHZYRO 300 mg starting on Day 0 and continued to receive TAKHZYRO every 2 weeks throughout the duration of the treatment period. The long-term safety of TAKHZYRO was the primary endpoint in the study.2
The long-term safety of TAKHZYRO was the primary endpoint in the open-label extension study.2
Effective HAE prevention in the long term
Patients taking TAKHZYRO for an average of 30 months experienced HAE attack reduction vs baseline2
in Attacks
- 0.25 mean monthly attack rate (N=209; baseline: 3.05)2
- 0.05 median monthly attack rate (range: 0.0-4.7; baseline: 2.00)9
- 84% reduction in moderate or severe attacks (N=209)2
- 93% reduction in attacks requiring acute treatment (n=106)2
All data presented are for TAKHZYRO 300 mg every 2 weeks unless otherwise indicated.1
SELECT IMPORTANT SAFETY INFORMATION
Adverse Reactions: The most commonly observed adverse reactions (≥10%) associated with TAKHZYRO were injection site reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory infection; headache; rash; dizziness; diarrhea; and myalgia. Less common adverse reactions observed included elevated levels of transaminases; one patient discontinued the trial for elevated transaminases.
Freedom from HAE attacks for extended periods of time when taking TAKHZYRO for an average of 30 months2
Zero Attacks for
All data presented are for TAKHZYRO 300 mg every 2 weeks unless otherwise indicated.1
*The percentage of days with zero attacks was calculated by counting the number of days in the treatment period without an HAE attack and dividing by the number of days the patient spent in the treatment period.9
Long-term, open-label extension data were consistent with the safety profile and efficacy in the pivotal trial.1,2
Who is the right patient for TAKHZYRO?
Hear from a patient who started TAKHZYRO after learning that their frequent HAE attacks were potentially preventable.1
SEE CASE STUDY
Explore safety profile
See safety information established in the clinical trials.
SEE SAFETY PROFILE
Who is the right patient for TAKHZYRO?
Hear from a patient who started TAKHZYRO after learning that their frequent HAE attacks were potentially preventable.1
Hear More From Experts
Explore safety profile
See safety information established in the clinical trials.
SEE SAFETY PROFILEAn open-label, multicenter study in patients with HAE as young as 2 years of age1
TAKHZYRO was studied in pediatric patients 2 to <12 years of age with HAE type I or II1
- 57% female10
- 43% male10
-
2 to <12 years of age10
- 4 patients aged 2 to <6 years
- 17 patients aged 6 to <12 years
of active treatment10
with C1-INH LTP10
- 24% had a history of laryngeal attacks10
The safety and pharmacokinetics of TAKHZYRO were the co-primary endpoints in the SPRING study.10
The SPRING Study Design
*Eligible patients underwent a 4- to 12-week baseline observation period before initiating treatment with TAKHZYRO.10
†Patients aged 2 to <6 years received 150 mg every 4 weeks for the 52-week treatment period.10
‡Patients aged 6 to <12 years were to receive 150 mg every 2 weeks for 52 weeks and had an option to switch to every 4 weeks if they were attack free for 26 weeks.10
Q4W=every 4 weeks.
The co-primary endpoints of this phase 3, open-label, multicenter pediatric trial were to assess the safety and pharmacokinetics of TAKHZYRO in 21 children with HAE type I or II (2 to <12 years of age). Efficacy was a secondary endpoint of the study, specifically the normalized number of investigator-confirmed HAE attacks during treatment compared to the baseline HAE attack rate during the 4- to 12-week observation period. The treatment period was 52 weeks, divided into 26-week treatment periods A and B. In treatment period A, patients aged 2 to <6 years (n=4) and 6 to <12 years (n=17) received TAKHZYRO 150 mg every 4 weeks and 150 mg every 2 weeks, respectively. In treatment period B, patients in the 2 to <6 years age group continued receiving 150 mg every 4 weeks, while patients in the 6 to <12 years age group were permitted to switch to 150 mg every 4 weeks if they were attack free during treatment period A. Seven patients aged 6 to 12 years switched to 150 mg every 4 weeks during treatment period B, and 1 patient aged 2 to <6 years switched to 150 mg every 2 weeks during treatment period B after experiencing recurrent attacks. Patients were followed up for 2 or 4 weeks, depending on their dosing schedule.1,10
Established effectiveness and safety profile in pediatric patients 2 to <12 years of age1
Use of TAKHZYRO for patients 2 to <12 years of age was supported by extrapolation of efficacy data from the HELP study, with additional pharmacokinetic analyses showing similar drug exposures between adults and pediatric patients; and safety and pharmacodynamic data from the SPRING study.1
Lanadelumab-flyo exposures in pediatric patients 2 to <12 years of age receiving TAKHZYRO 150 mg every 2 weeks or every 4 weeks were comparable to those in adult patients receiving TAKHZYRO 300 mg every 2 weeks10
- Pharmacokinetics (Co-primary Endpoint): Patients aged 2 to <12 years taking TAKHZYRO in the 52-week open-label study experienced systemic exposure to TAKHZYRO10
Limitations
Because this was a noncontrolled, open-label study that enrolled 21 pediatric patients and lacked statistical hypothesis testing, these data have less evidentiary value than a double-blind, placebo-controlled study. Further confirmatory studies are required to draw any conclusions from these data.10
Patients aged 2 to <12 years taking TAKHZYRO in the 52-week open-label study experienced attack reduction vs baseline1,10
-
95% reduction in attacks on average vs baseline (N=21)10*
- Mean monthly attack rate at baseline (during observation period): 1.84 (N=21)10
- Mean monthly attack rate on treatment: 0.08 (N=21)10
- 76% of patients experienced freedom from attacks for the entire 52-week study (n=16)10
- 99.5% of days on average with zero attacks during the entire treatment period (n=21)10
All data presented are for the total population of pediatric patients taking TAKHZYRO 150 mg every 2 or every 4 weeks.
*Baseline was defined as the frequency of HAE attacks in pediatric patients before they started TAKHZYRO.10
SELECT IMPORTANT SAFETY INFORMATION
Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients <2 years of age have not been established.
Who is the right patient for TAKHZYRO?
Hear from a patient who started TAKHZYRO after learning that their frequent HAE attacks were potentially preventable.1
SEE CASE STUDY
Explore safety profile
See safety information established in the clinical trials.
SEE SAFETY PROFILEHR-QoL prespecified exploratory endpoint
The burden of HAE goes beyond the attack
The unpredictable nature of HAE can affect various facets of a patient’s life.11
In the HELP study, quality of life (QoL) measures were evaluated using the AE-QoL and EQ-5D-5L questionnaires12
Limitations: These results should be interpreted with caution as they are based on patient recall and are observational/descriptive in nature. These data were also from an exploratory objective and had less evidentiary value than the primary and secondary objectives. The AE-QoL was administered to 10 adolescent patients in the study, an age group for which the instrument was not validated.12
For the EQ-5D-5L questionnaire, an instrument used to measure health status on a given day, no differences were observed. The nondisease-specific EQ-5D-5L questionnaire was administered on days 0, 98, and 182.12
Significantly more patients taking TAKHZYRO vs placebo experienced improvements in AE-QoL in the 6.5-month HELP study12:
- 81% of patients receiving TAKHZYRO 300 mg Q2W (95% CI, 61-93; n=26) experienced improvement in AE-QoL total score vs 37% of patients taking placebo (P<0.05; 95% CI, 22-54; n=38)12
- Patients receiving TAKHZYRO 300 mg Q2W were 7.2 times more likely to achieve improvement in AE-QoL total score vs patients taking placebo (P<0.01)12
Definitions: The AE-QoL is a validated, angioedema-specific questionnaire in adults that was administered monthly, consisting of 4 domains (functioning, fatigue/mood, fears/shame, nutrition) and total scores. The minimal clinically important difference (MCID) is the minimum change in score that is meaningful to patients. For the AE-QoL total score, the predefined MCID is a reduction of 6 points.12-14
AE-QoL=Angioedema Quality of Life Questionnaire; EQ-5D-5L=5-level EuroQol 5-dimensional; HR-QoL=health-related quality of life; Q2W=every 2 weeks.
