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Gene therapy for hemophilia B offers long-term bleed protection with a one-time infusion

admin June 18, 2023

This is a paid public announcement from CSL Behring and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to the CSL Behring website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

The current standard of care for moderate to severe hemophilia B, factor IX prophylactic therapy, does offer bleed protection. However, it requires lifelong, routine infusions to maintain protective factor levels, and those who regularly infuse factor IX replacement products can still experience breakthrough bleeds, leading to joint damage, pain, and reduced quality of life. There is a need for a treatment option that offers consistent bleed protection with a one-time infusion that lasts years instead of weeks.

After years of scientific research and clinical studies, that option is here—HEMGENIX^® (etranacogene dezaparvovec-drlb), the first and only gene therapy for hemophilia B.*

Hemophilia B is an appropriate target for treatment with gene therapy

Hemophilia B is caused by a mutation of a single gene—the F9 gene. Approaches using gene therapy to treat inherited conditions stemming from a single genetic mutation, including hemophilia B, have predominantly focused on the delivery of a working, or functional, gene using a viral vector.

Hemophilia B is an appropriate target for treatment with gene therapy because it is caused by a mutation of a single gene, the F9 gene, which is small enough that it can be packaged into an adeno-associated viral (AAV) vector.

How HEMGENIX gene therapy for hemophilia B works

HEMGENIX uses a gene therapy approach called gene transfer. Gene transfer therapy for hemophilia B starts by developing a package of genetic instructions—the functional, or working, gene. Then AAV vectors are created, which will eventually enter targeted liver cells. The package of genetic instructions is loaded into an AAV vector shell, acting as a delivery truck. Through a single IV infusion, the delivery truck heads toward the liver with its package.

Once delivered into the liver cells, the package of instructions is unloaded, enabling the liver to start generating factor IX, with the goal of allowing a person to produce their own elevated and protective levels of factor IX. After delivering its package, the AAV vector shell is broken down and eliminated. However, the genetic instructions remain to continue producing factor IX.

Built on science you can trust

Gene therapy is built on decades of clinical research. The first patients received gene therapy in 1970, and there are more than 250 AAV-based clinical trials currently underway across a variety of conditions. So not only is gene therapy with HEMGENIX EMHa great fit for hemophilia B, it’s based on years of scientific research.

Interested in learning more about the science behind HEMGENIX, a one-time infusion that offers years of consistent bleed protection? Explore all that gene therapy might offer for people with hemophilia B today!

*HEMGENIX was studied in a clinical trial of 54 male adults with moderately severe or severe hemophilia B. All people in the trial were taking factor IX prophy to treat their hemophilia B and were observed for at least 6 months on prophy before receiving HEMGENIX.

†AAV5, adeno-associated viral vector serotype 5.

IMPORTANT SAFETY INFORMATION

What is HEMGENIX?

HEMGENIX^®, etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of adults with hemophilia B who:

Currently use Factor IX prophylaxis therapy, or
Have current or historical life-threatening bleeding, or
Have repeated, serious spontaneous bleeding episodes.

HEMGENIX is administered as a single intravenous infusion and can be administered only once.

What medical testing can I expect to be given before and after administration of HEMGENIX?

To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed.

HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids.

What were the most common side effects of HEMGENIX in clinical trials?

In clinical trials for HEMGENIX, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience.

What should I watch for during infusion with HEMGENIX?

Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest tightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve.

What should I avoid after receiving HEMGENIX?

Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX.

Please see full prescribing information [LINK TO: https://labeling.cslbehring.com/PI/US/Hemgenix/EN/Hemgenix-Prescribing-Information.pdf] for HEMGENIX.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch [LINK TO: www.fda.gov/medwatch], or call 1-800-FDA-1088.

You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958.

HEMGENIX is manufactured by uniQure Inc. and distributed by CSL Behring LLC. HEMGENIX^® is a registered trademark of CSL Behring LLC.

www.CSLBehring.com USA-HGX-0464-MAY23

Women and hemophilia: evolving knowledge and raising awareness

admin June 4, 2023

I love sharing stories from our community, and have been a voice for hemophilia patients since 1990, when we published Raising a Child with Hemophilia. It included stories from 125 families, the first ever such publication. Let’s continue that tradition! In this blog, Sanofi introduces you to a woman with hemophilia, Kyrie, who shares her unique story.

Sponsored by Sanofi

While hemophilia is more common in men, women can also experience symptoms and receive a diagnosis. Because of a traditional misconception that women are only carriers of hemophilia, they have historically not been tested and treated for the condition.¹ This is changing, thanks to emerging understanding and awareness of hemophilia in women.

Kyrie Smith lives with hemophilia and works as a Community Relations and Education (CoRe) manager at Sanofi. We sat down with her to hear about her hemophilia journey.

Please note that Kyrie’s story is hers alone. While there are common threads, everybody’s experiences with hemophilia will be different.

A legacy of advocacy

Kyrie’s family history with hemophilia goes back to her grandmother. According to Kyrie, her grandmother was one of the first women to receive access to on-demand factor treatment for bleeds as they occurred. Kyrie credit’s her grandmother’s self-advocacy with helping her get treatment at a time when it was uncommon for women to be diagnosed, let alone treated.

“The ability for my grandmother to be prescribed factor to control a bad leg bleed was quite novel at the time,“ Kyrie says. “While she is no longer with us anymore, I often find myself thinking about her strength and resilience.”

Hemophilia affects both women and men in Kyrie’s family. Since Kyrie was a carrier of hemophilia and could become symptomatic, her mother advocated for Kyrie’s factor activity levels to be checked during her brother’s annual appointments.

“I’m thankful for my mother’s persistence, as I was diagnosed so early in my childhood, when many women— including my mother—are often diagnosed later in life,” Kyrie says. “I am very proud to come from a long line of strong women who have advocated for the health of their family as well as themselves.”

Strength in sisterhood

Kyrie was first diagnosed as a symptomatic carrier of hemophilia and was prescribed a treatment to address bleeds and other symptoms as they occurred. A few years later, her diagnosis was updated to mild hemophilia.

“This change was due to the strong women and advocates in the hemophilia community that helped evolve the definition of symptomatic carrier to mild hemophilia, which is defined by factor activity levels,” Kyrie says. “I am honored to now join them in their work to increase visibility and voices of women with hemophilia.”

By working with her healthcare team, Kyrie has been able to manage her condition. That doesn’t mean, however, that the situation is without its challenges.

“From missing sports practices in high school to switching cardio workouts to avoid overworking my joints and managing pain, I’ve had to make some compromises along the way,” Kyrie says.

She’s grateful for the support and encouragement she’s received from the hemophilia community to help her get through difficult times. Kyrie started attending hemophilia camps at age 7, an experience she considers central to her continued sense of community.

“By having a mentor to look up to, or a peer to talk through an issue with, I’ve made lifelong friends from my time at hemophilia camps and other chapter or national events,” says Kyrie.

When to start asking questions

Awareness, testing, and diagnosis of hemophilia in women are increasing.¹ It can be difficult, however, to know whether the bleeding you experience is normal or abnormal. When in doubt, it’s best to speak to your doctor to discuss what’s going on.

The common signs of hemophilia in women include:²

Heavy menstrual periods, such as soaking through one or more pads or tampons every 2 hours or less³
Low in iron or have anemia
Frequent nosebleeds that last longer than 10 minutes
Bleeding from cuts lasting longer than 5 minutes
Easily bruised (raised and larger than a quarter, happening on a weekly basis)
Joint bleeds (pain, swelling, unusual sensations, warmth, loss of motion)
Family history of a bleeding disorder
Heavy bleeding from surgery

If you or someone you care about is experiencing the signs and symptoms above, consider reaching out to a doctor to explain what’s happening and get more information.

Coming full-circle

Kyrie now works as a Sanofi CoRe, which gives her the opportunity to pay forward the information and connection she has experienced from within the hemophilia community.

“Because the hemophilia community has played such a large role in my life, I want to continue giving back, being a resource for the next generation,” Kyrie says. “As a CoRe, I am able to connect with various members of the community no matter where they might be in their hemophilia journey. It could be a new parent navigating hemophilia care for their child, or it could be a young adult working to manage their hemophilia care independently.”

While everyone’s experiences with hemophilia are unique, Kyrie’s personal path gives her extra insight into what members of the community are going through.

“When I have the opportunity to connect with a young girl who is having hemophilia symptoms and needs to advocate for herself, I can really relate because I’ve been in her shoes,” Kyrie says. “The road to diagnosis and treatment can be long and confusing, but there are so many reasons to keep going and so many people to help you do just that. I hope by sharing my story, others will too, and together, we can continue empowering the hemophilia community to advocate for their care and supporting those in the earliest stages of their hemophilia journey.”

If you have a family history of hemophilia or you’re experiencing symptoms, you’re not alone. Reach out to your doctor for more information.

To learn more about women and hemophilia, including how it’s inherited, how it presents, and options for treatment, visit RedefiningHemophilia.com.

This is a paid public announcement from Sanofi and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to a Sanofi website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

“Women can have hemophilia, too.” Centers for Disease Control and Prevention, https://www.cdc.gov/ncbddd/hemophilia/features/women-and-hemophilia.html
“Women and bleeding disorders.” National Hemophilia Foundation, https://www.hemophilia.org/bleeding-disorders-a-z/overview/women-and-bleeding-disorders
Menorrhagia (heavy menstrual bleeding).” Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/menorrhagia/symptoms-causes/syc-20352829

MAT-US-2303664-v1.0-05/2023

Discover a treatment that could change how you manage your hemophilia A

admin May 28, 2023

This is a paid public announcement from Sanofi and does not constitute an endorsement of products or services. When you click on the links in this blog entry, you will be directed to a Sanofi website. LA Kelley Communications always advises you to be a savvy consumer when contacting any company; do not reveal identifying information against your will.

If your life has been touched by hemophilia A, you know it can be full of unknowns. Bleeds can be painful, happen without warning, and limit physical activity, which is why it’s critical to stay on top of them. Sanofi launched ALTUVIIIO [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl]—a hemophilia A Factor VIII replacement therapy that provides proven bleed protection.

Here are 4 reasons to consider ALTUVIIIO:

1. HIGHER FACTOR LEVELS THAT LAST LONGER
With just one weekly ALTUVIIIO infusion, factor levels remain in the near-normal to normal range (>40%) for most of the week and stay above 18%,^* on average, in adults.

*Average trough levels were 18% for adults 18 years and older, 9% for adolescents aged 12 years to under 18 years, 10% for children aged 6 years to under 12 years, and 7% for children aged 1 year to under 6 years.

^‡This is information from a study of 13 previously treated adults with severe hemophilia A that had the goal of comparing how long ALTUVIIIO, Adynovate^® [Antihemophilic Factor (Recombinant), PEGylated], and Advate^® [Antihemophilic Factor (Recombinant)] stayed in the body after 1 dose. Half-life was 43 hours for ALTUVIIIO, 15 hours for Adynovate, and 11 hours for Advate.
Adynovate and Advate are registered trademarks of Baxalta Incorporated, a Takeda company.

EHL=extended half-life; SHL=standard half-life.

ALTUVIIIO offers not only weekly prophylaxis use, but also on-demand bleed control and perioperative management. Regardless of how you use it, you can expect the same infusion process.

2. STUDIED—AND PROVEN—BLEED PROTECTION
Before we dig into the numbers, it’s helpful to know how ALTUVIIIO was studied and to understand its safety profile.

For one year, the XTEND-1 study looked at treatment in 159 adults and adolescents. Participants were divided into 2 groups. Both groups used mean and median annualized bleed rates (ABRs) to evaluate the efficacy of ALTUVIIIO. Finding people’s mean ABR was the primary goal of the study.

Safety evaluated in 159 people taking ALTUVIIIO in the XTEND-1 study showed that:

21% of people had headache (33 people)
16% of people had joint pain (26 people)
6% of people had back pain (9 people)

In 67 children taking ALTUVIIIO in the ongoing XTEND-Kids study:

1% of children had headache (1 child)

In XTEND-1 and XTEND-Kids, people taking ALTUVIIIO had:

0 inhibitors
0 serious allergic reactions

Although no inhibitors were found, and no serious allergic reactions occurred in clinical studies, inhibitors and serious allergic reactions are possible with ALTUVIIIO.

Group 1
This group consisted of 133 people aged 12 years and older who had prior prophylaxis therapy and switched to ALTUVIIIO weekly prophylaxis. This group included 1 female participant. Efficacy of prophylaxis was evaluated in 128 of these patients.

The primary outcome showed a mean of <1 (0.7) bleeds per year (the median ABR was 0).^‡

Here’s a look at how the study measured bleed rates:

Median ABR was the middle number of all ABRs, when ABRs were ordered from least to greatest
Mean ABR was the average number based on everyone’s ABRs

It’s also worth noting that 78 of the people in Group 1 participated in a separate study to measure their ABRs on their prior prophylaxis. These 78 people went from 3 bleeds to less than 1 bleed a year. That’s a 77% reduction in yearly bleeds!^‡

Group 2
People in this group (28 participants) switched to ALTUVIIIO on demand from prior on-demand therapy for 26 weeks, and then were treated with ALTUVIIIO prophylaxis for another 26 weeks.

This group also saw striking results. On average, people who switched from ALTUVIIIO on demand to ALTUVIIIO prophylaxis went from 21 bleeds to less than 1 bleed a year (mean ABR 0.7). That’s a 97% mean reduction in yearly bleeds.^‡

And over the 26 weeks on ALTUVIIIO prophylaxis, 77% of people had 0 bleeds.^‡

Both groups showed significant improvement in bleed protection with ALTUVIIIO prophylaxis.

^‡Data based on treated bleeds.

3. FEEL CONFIDENT YOUR JOINTS ARE PROTECTED

The XTEND-1 study also examined target joint bleeds. When evaluating joint results at 52 weeks in the 128 people who participated in the XTEND-1 study, 72% of people had 0 joint bleeds‡ on prophylaxis after switching to ALTUVIIIO. 100% of target joints were resolved.

Target joints:

Are 3 or more spontaneous bleeds in a major joint within a period of 6 consecutive months
Were considered resolved if 2 or fewer bleeds occurred in the target joint within 12 months

4. THE FEWEST WEEKLY INFUSIONS AMONG FACTOR VIII PROPHYLAXIS TREATMENTS

While most people with hemophilia grow accustomed to infusing, fewer infusions are generally preferred. In studies, ALTUVIIIO clearly outlasted other Factor VIII replacement therapies, meaning ALTUVIIIO takes longer to be reduced by half in the body, and therefore lasts for a longer period.

So instead of needing up to 4 infusions a week with other treatments, patients on ALTUVIIIO infused only once per week.

ALTUVIIIO offers the fewest weekly infusions among Factor VIII prophylaxis treatments.

^†This is information from a study in 13 previously treated adults with severe hemophilia A that had the goal of comparing how long ALTUVIIIO, Adynovate^® [Antihemophilic Factor (Recombinant), PEGylated], and Advate^® [Antihemophilic Factor (Recombinant)] stayed in the body after 1 dose. Half-life was 43 hours for ALTUVIIIO, 15 hours for Adynovate, and 11 hours for Advate.
^§Doses and dosing intervals may be adjusted.
Adynovate and Advate are registered trademarks of Baxalta Incorporated, a Takeda company.

Now that you’ve learned about a few of the ways ALTUVIIIO protects you from bleeds, you may be considering a conversation with your doctor about your treatment plan. Our Doctor Discussion Guide can help. It offers a list of helpful questions to help you jump-start the conversation. You can also connect with your local Sanofi Community Relations and Education (CoRe) Manager, who can share additional resources and provide education.

INDICATION
ALTUVIIIO™ [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is an injectable medicine that is used to control and reduce the number of bleeding episodes in people with hemophilia A (congenital Factor VIII deficiency).

Your healthcare provider may give you ALTUVIIIO when you have surgery.

IMPORTANT SAFETY INFORMATION

What is the most important information I need to know about ALTUVIIIO?
Do not attempt to give yourself an injection unless you have been taught how by your healthcare provider or hemophilia center. You must carefully follow your healthcare provider’s instructions regarding the dose and schedule for injecting ALTUVIIIO so that your treatment will work best for you.

Who should not use ALTUVIIIO?
You should not use ALTUVIIIO if you have had an allergic reaction to it in the past.

What should I tell my healthcare provider before using ALTUVIIIO?
Tell your healthcare provider if you have had any medical problems, take any medications, including prescription and non-prescription medicines, supplements, or herbal medicines, are breastfeeding, or are pregnant or planning to become pregnant.

What are the possible side effects of ALTUVIIIO?
You can have an allergic reaction to ALTUVIIIO. Call your healthcare provider or emergency department right away if you have any of the following symptoms: difficulty breathing, chest tightness, swelling of the face, rash, or hives.

Your body can also make antibodies called “inhibitors” against ALTUVIIIO. This can stop ALTUVIIIO from working properly. Your healthcare provider may give you blood tests to check for inhibitors.

The common side effects of ALTUVIIIO are headache, joint pain, and back pain.

These are not the only possible side effects of ALTUVIIIO. Tell your healthcare provider about any side effect that bothers you or does not go away.

Please see full Prescribing Information.

MAT-US-2209658-v1.0-05/2023

New Survey Spotlights Ongoing Concerns for People Living with Hemophilia B

admin April 30, 2023

Carefully controlled schedules. Undercurrents of uncertainty. Persistent pain. People who are living with hemophilia B, and those who love them, face a lifetime of managing the complexities of this condition.

While significant advancements have been made in the treatment of hemophilia B, there is still a desire for new treatment options to address unmet needs for people with moderate to severe forms of the condition.

In fact, a recent CSL Behring-sponsored survey on the burdens of living with hemophilia B found that even with treatment, people with hemophilia B are still experiencing spontaneous bleeds and joint pain, and would consider switching to a new therapy that may be more effective. The online survey conducted by CSL Behring in partnership with the Coalition for Hemophilia B included 110 people with the rare bleeding disorder who are on either short-term or long-term prophylactic treatment.* The survey revealed that during a six-month period, respondents reported an average of 4.2 spontaneous bleeds and 2.2 joints bleeding three or more times.

Additionally, 87% of respondents reported experiencing joint pain at least a few times a month.

“The survey really highlighted the concerns and challenges that people with hemophilia B still face,” said Kim Phelan, Chief Operating Officer of The Coalition for Hemophilia B. “Spontaneous bleeds, joint damage and joint pain are just a few of the burdens that some in the hemophilia B community must live with.

With up to 156 intravenous infusions per year, people with hemophilia B are also at risk for vein collapse.

The life-long effects of living with and managing hemophilia B however aren’t just physical. More than 40% of people living with hemophilia B experience depression, anxiety, or other psychological disorders.

As new treatments become available to potentially address the unmet needs within the hemophilia B community, discussion with healthcare professionals on treatment goals is essential. It’s time to ask, “Is there a better treatment option for me?”

*Short-term prophylaxis is prolonged treatment following a bleed until full recovery and prophylaxis prior to physical activity. Long-term prophylaxis is regular preventative injections. Of the 110 people surveyed, 29 were being treated with short-term prophylaxis only, 74 were being treated with long-term prophylaxis only, and 7 were being treated with both short-term and long-term prophylaxis.

www.CSLBehring.com USA-HGX-0330-APR23

Boost Mental Well-Being with Empowerment

admin April 24, 2022

Sponsored content by Sanoﬁ

May is Mental Health Awareness Month. Since it is not uncommon for people with hemophilia to experience higher rates of mental health issues, this is an important topic for the bleeding disorders community. If you or someone you care for has hemophilia, it can be a time to be mindful of mental health and consider taking empowering steps toward improved well-being.

Studies have shown that nearly four out of 10 adults living with hemophilia met the criteria for depression,¹ and that people with hemophilia and depression are less likely to adhere to a proper treatment regimen.² Withdrawing from friends, family, and the community can also happen over time, all of whom may help with maintaining a well-rounded and connected life.

Mental health not only aﬀects a person emotionally, but also inﬂuences physical well-being. “There
is no health without mental health,” said Debbie de la Riva, CEO of Mental Health Matters Too.
“When someone is struggling with a mental health disorder, he/she is less likely to engage in
healthy self-care behavior, such as getting enough exercise. This can have a lasting, negative
impact on their joints and increase the risk of bleeds.”

If you are struggling with your mental health, it is important to talk to someone about it and
possibly seek treatment. Recognizing and acknowledging your condition is critical to managing
mental health. Visit the National Alliance on Mental Illness to learn about the signs and symptoms
of common mental health conditions, such as depression and anxiety, and to better recognize them in
yourself or a loved one. Through honest, open conversation, you can help yourself and others by
breaking down stigmas associated with mental health.

“I encourage people to recognize what mental health conditions look like and how to have that
conversation,” de la Riva says. “It’s time we break the stigma and educate ourselves.”

Another way to potentially improve mental well-being is by taking steps toward a greater sense of

empowerment. Empowerment allows patients and caregivers to have a sense of control over mindsets
and the conﬁdence to make choices and solve challenges that arise. Some steps you can take to help
increase your sense of empowerment include:

Embracing uniqueness
What traits make you special? Think about characteristics like creativity, gratitude, and bravery.
These are strengths that can help you navigate diﬃcult situations.
Engaging in self-advocacy
Self-advocacy means understanding your needs and speaking up for yourself in order to have those
needs met.
Creating empowering partnerships
Partners in empowerment support you in your decisions. They can be friends, family, a care team,
others with hemophilia, and other people in your life who believe in you and your abilities.

Empowerment is an active process that can be nurtured, practiced, and developed over time. One way
to practice empowerment is through visualization. The activity below can be used to help you
visualize the situations, behaviors, and people who give you conﬁdence in navigating life:

On a piece of paper, write a word that describes a situation where you feel in control of your surroundings and empowered to speak about and make decisions regarding your hemophilia. Make that word so large it ﬁlls as much of the space as possible.
Fill in the space around your big word with actions you take in that situation that make you
feel conﬁdent.
Write down the names of people who support you, continuing to ﬁll in as much space as you
can. Post this somewhere you will see it often as a reminder of what makes you feel empowered.
Sanoﬁ is committed to empowering people with hemophilia. If you’d like to learn more, you can also connect with your local Sanoﬁ Community Relations and Education, or CoRe, Manager, who can provide
education and share resources for additional information.

¹https://pubmed.ncbi.nlm.nih.gov/22642565/#:~:text=Adult%20patients%20with%20haemophilia%20have,h ealth%20outcomes%20and%20treatment%20adherence
²https://www.dovepress.com/interrelationship-between-depression-anxiety-pain-and-treatment-adhere-pe er-r eviewed-fulltext-article-PPA

MAT-US-2201856-v1.0-03/2022