Caleb, age 7, living with NF1 PN. Caleb is not a Koselugo patient.
Time to response1*
(For 33 patients who responded at the DCO of June 2018)
Month
Expected adverse reactions
(DCO 2019)
What your Koselugo patients may experience during the first year of treatment
Below is an overview of the first year of tumor response and adverse reactions, based on the SPRINT Phase 2 Stratum 1 study (N=50). Individual patient results may vary, but this visual can help patients and caregivers understand the median time to response and onset of adverse reactions that were reported in the SPRINT study.
Tap or click the arrow below to scroll the entire timeline.
Earliest tumor response 1
- (3.3 months)
Median time to onset of response 1†
- (7.2 months)
42 %
(14/33)
responded within
4 cycles 2
(3.7 months)
73 %
(24/33)
responded within
8 cycles 2
(7.4 months)
97 %
(32/33)
responded within
12 cycles 2
(11 months)
0
1
2
3
4
5
6
7
8
9
10
11
12
+1 to 12
weeks
- Acneiform rash 3
- Nausea 4
- Dry mouth 4
- Diarrhea 4
- Vomiting 4
- Fatigue 4
+3
months
- Stomatitis 3
- Dry skin 4
- Increased CPK 3
+4 to 8
months
- Hair color changes 4
- LVEF reduction 3‡
- Pyrexia 4
+8 to 12
months
- Paronychia 3
+12
months
- Blurry vision 3§
Any of the efficacy results or adverse reactions may occur at any time during the course of treatment.1
Therefore, routine monitoring for adverse reactions is critical. The most common adverse reactions (≥40%) are vomiting, rash (all), abdominal pain, diarrhea, nausea, dry skin, musculoskeletal pain, fatigue, pyrexia, acneiform rash, stomatitis, headache, paronychia, and pruritus. An increased risk of bleeding may occur in patients who are coadministered vitamin K antagonists or antiplatelet antagonists with Koselugo. Monitor for bleeding in these patients.
Advise your patient or their caregiver to contact their care team about any adverse reactions experienced during treatment.
*Latest tumor response was 1.6 years (data cutoff June 2018).1
†Time to response was defined as the time from study treatment initiation until the pre-cycle volumetric MRI assessment of the first documentation of complete response or a subsequently confirmed partial response.2
‡Cardiomyopathy, defined as a decrease in
LVEF ≥10% below baseline occurred in 23% of 74 pediatric patients
receiving Koselugo in SPRINT. Four percent of patients experienced
decreased LVEF below the institutional LLN. Grade 3 decreased LVEF
occurred in one patient and resulted in dose reduction. All
patients with decreased LVEF were asymptomatic and identified
during routine echocardiography. Decreased LVEF resolved in
71% of these patients.1
§Blurred vision, photophobia, cataracts,
and ocular hypertension occurred in 15% of 74 pediatric patients
receiving Koselugo in SPRINT. Blurred vision resulted in dose
interruption in 2.7% of patients. Ocular toxicity resolved in 82%
of
11 patients.1
AE=adverse event; CPK=creatine phosphokinase; DCO=data cutoff; LLN=lower limit of normal; LVEF=left ventricular ejection fraction; MRI=magnetic resonance imaging; NF1=neurofibromatosis type 1; PN=plexiform neurofibromas.
Dosing & AE Management Guide
A guide that provides dosing information and presents how specific toxicities were managed in the SPRINT study, based on institutional policies and guidelines.
Download guide
Treatment Tracking Journal
Help your patients and their caregivers keep track of their treatment experience with this helpful guide.
Download guideHear from real caregivers of patients on Koselugo
Meet Kim and her son Quentin, a Koselugo patient for over 10 years
Kim reflects on Quentin’s journey with NF1 PN, beginning with his diagnosis at just 22 months old. Kim discusses the challenges they've faced, including multiple surgeries and tumor regrowth, and shares insights into Quentin’s experience with Koselugo.
"NF1 does not define who he is as a person."
Kim:
This is my son, Quentin.
He’s a cool kid. He’s just really cool.
Quentin and his brother are a little bit competitive. But they get along really well. They’ve got each other’s backs.
Quentin is a fighter, for sure. At a very young age, he was diagnosed with Neurofibromatosis type 1 (NF1) related plexiform neurofibromas or PN, benign tumors that can grow along nerves anywhere in the body.
NF1 is his diagnosis. But that does not define who he is as a person.
At about 17 months, he developed a cluster of, at the time, I didn’t know neurofibromas on his cheek.
So, I brought it up to his physician and eventually she recommended an MRI, and it came back that he has Neurofibromatosis (NF1).
He was diagnosed with PN at 22 months. With PN, even with debulking, the tumor can grow back. It would grow in 23% to 33% in volume every three to six months.
Quentin’s tumor got so large that I could put it in the palm of my hand.
He’s had 10 surgeries and countless complications.
Sometimes we cry together. And we have really hard conversations about where NF takes you, you know, and things that he has to deal with. That is really hard, and you compartmentalize it. You become, at that point you’re a caregiver and not a parent.
I mean even now he gets stares. You know one time somebody asked my older son if he punched him in the face.
His brother is definitely his protector, probably one of the best educators and advocates he could ever have.
When Quentin was 5, our doctor told us about a new trial for a drug called selumetinib which would later be called KOSELUGO®.
The doctors told us about possible side effects, including the most common ones such as vomiting and stomach pain.
They felt that KOSELUGO could potentially decrease the size of his tumors. He had to do the preliminary testing and all of that first, but we signed on.
Quentin was 1 of 50 patients that were on the original trial. After FDA approval, whenever there were any questions along the way, we could utilize OneSource.
Which is a free, personalized patient support program offered by Alexion. OneSource was amazing. Because as a parent you’re juggling so many things and then you add that on top of it to know that there is an advocate for you and a resource that you can go to, it’s, it’s very nice to have.
KOSELUGO’s definitely been a good fit for Quentin. He just had an MRI a month ago, and he is stable. Stable is beautiful.
He takes KOSELUGO every 12 hours, so twice a day and it’s part of life.
Quentin’s side effects with KOSELUGO have, they’ve been pretty minimal. He did have some diarrhea. He did have some issues with acne.
Of course, this has been Quentin’s experience, and others may have a different experience with KOSELUGO.
Quentin:
Since taking KOSELUGO, I’ve noticed a big difference in my tumor growth.
I feel like I can do everything almost anybody else can.
Kim:
Quentin is in a good place now, emotionally, and mentally. I feel like he is living his best life.
We still have doctor appointments, but it’s very secondary. It is a sense of relief that he’s on KOSELUGO, that we could breathe a little.
I love being a mom, it’s one of the most rewarding things I think a person could ask for. I can’t imagine not having them.
And I’m so thankful for all KOSELUGO has done for him.
Meet Natalie and her daughter Kamie, a Koselugo patient for over 1 year
Natalie discusses Kamie's NF1 PN journey, from learning how critical timely evaluation and intervention are to sharing Kamie's experience with Koselugo.
"The doctors have been pleased with her results on Koselugo. She has not had tumor growth."
Natalie:
This is my daughter, Kamie. She’s 3 years old.
She loves to tell stories. She likes to sing; She likes to dance. She is definitely very feisty.
When she turned 3, she was diagnosed with Neurofibromatosis type 1 (NF1) related Plexiform Neurofibromas (PN), which is when benign tumors grow along nerves throughout the body.
We know it’s a lifelong journey for our daughter, and so we are in it. We’re ready to move forward and keep it positive.
Right before she was turning 3, we started to potty train her.
In doing so, we noticed her peeing quite frequently, almost all the time.
I assumed maybe she had a UTI or something. Her three-year old wellness checkup was coming up. So, I figured we would talk to the doctor.
We also had noticed that one side of her buttocks was bigger than the other side. There was some discoloration on the bigger side. The doctor was concerned and so they did an ultrasound on her bladder and then we found out that there was a mass.
After an MRI, she was diagnosed with NF1 with PN.
I cried a lot when I was by myself. My husband and I understood the seriousness and had a lot of worries.
The biggest thing I learned is that this disease will impact her for the rest of her life.
That it was a genetic disorder that she was born with. Because NF1, PN, can grow rapidly in early childhood, timely evaluation and intervention are critical and can help change the disease trajectory.
I have a lot of friends with kids, and they don’t have to worry about any of this extra stuff.
How would this affect her growing up? What treatments were available.
Fortunately, our doctor told us there is a treatment called KOSELUGO® (selumetinib).
It's the first prescription medicine that is used to treat children two years of age and older with Neurofibromatosis type 1, NF1, Plexiform Neurofibromas, PN.
The doctor told us that KOSELUGO would shrink the PN.
As with any medicine, it’s possible to experience side effects with KOSELUGO. These side effects may include vomiting, stomach-area pain, nausea, and dry skin.
After discussing the side effects with our doctor, we decided to move forward with the treatment.
We also learned about OneSource; a free, personalized patient support program offered by Alexion.
I found that OneSource was valuable. It was at a time where we were not sure, you know, what the future held.
So far, her doctors have been pleased with her results on KOSELUGO. She has not had tumor growth.
The side effects Kamie has had is just the dry skin. It hasn’t been severe.
Kamie had a little bit of difficulty swallowing the pill, as expected for a three-year old. She didn’t know how to do it, but she caught on very quickly.
Kamie no longer has to fast while taking KOSELUGO.
It made nighttime so much easier because we didn’t have to make sure she finished dinner by a certain time.
Of course, this is Kamie’s experience, and may be different from others.
We’re still working on that potty training. We’ve accepted NF1 PN as part of our lives.
It definitely is comforting to know that KOSELUGO is a treatment option.
Kamie does not know any different. She feels like a normal kid.
Because of KOSELUGO, I am hopeful that Kamie can live with her NF1 PN. I am hopeful that Kamie will have a fulfilling life.
OneSource is a free, personalized patient support program offered by Alexion. Whether your patient is newly diagnosed or has had their condition for some time, our specialists are available for patients and caregivers.
Learn moreIMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Cardiomyopathy. A decrease in left
ventricular ejection fraction (LVEF) ≥10% below baseline occurred
in pediatric
patients who received Koselugo in SPRINT with some
experiencing decreased LVEF below the institutional lower limit of normal
(LLN), including one patient with Grade 3. All patients with decreased
LVEF were asymptomatic and identified during routine echocardiography.
The safety of Koselugo has not been established in patients with a history
of impaired LVEF or a baseline ejection fraction that is below the institutional
LLN. Assess ejection fraction by echocardiogram prior to initiating treatment,
every 3 months during the first year of treatment, every 6 months thereafter,
and as clinically indicated. Withhold, reduce dose, or permanently discontinue
Koselugo based on severity of adverse reaction. In patients who interrupt
Koselugo for decreased LVEF, obtain an echocardiogram or a cardiac MRI
every 3 to 6 weeks. Upon resolution of decreased LVEF, obtain an echocardiogram
or a cardiac MRI every 2 to 3 months.
Ocular Toxicity. Blurred vision,
photophobia, cataracts, and ocular hypertension
occurred. Retinal
pigment epithelial detachment (RPED) occurred in the pediatric population
during treatment with single agent Koselugo and resulted in permanent discontinuation.
Conduct ophthalmic assessments prior to initiating Koselugo, at regular
intervals during treatment, and for new or worsening visual changes. Permanently
discontinue Koselugo in patients with retinal vein occlusion (RVO). Withhold
Koselugo in patients with RPED, conduct ophthalmic assessments every 3
weeks until resolution, and resume Koselugo at a reduced dose.
Gastrointestinal Toxicity. Diarrhea
occurred, including Grade 3. Diarrhea resulting in permanent discontinuation,
dose interruption or dose reduction occurred. Advise patients to start
an anti-diarrheal agent (eg, loperamide) and to increase fluid intake immediately
after the first episode of diarrhea. Withhold, reduce dose, or permanently
discontinue Koselugo based on severity of adverse reaction.
Skin Toxicity. Rash occurred in 91% of 74 pediatric patients. The most frequent rashes included dermatitis acneiform (54%), maculopapular rash (39%), and eczema (28%). Grade 3 rash occurred, in addition to rash resulting in dose interruption or dose reduction. Monitor for severe skin rashes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.
Increased Creatine Phosphokinase (CPK). Increased CPK occurred, including Grade 3 or 4 resulting in dose reduction. Increased CPK concurrent with myalgia occurred, including one patient who permanently discontinued Koselugo for myalgia. Obtain serum CPK prior to initiating Koselugo, periodically during treatment, and as clinically indicated. If increased CPK occurs, evaluate for rhabdomyolysis or other causes. Withhold, reduce dose, or permanently discontinue Koselugo based on severity of adverse reaction.
Increased Levels of Vitamin E and Risk of Bleeding. Koselugo capsules contain
vitamin E which can inhibit platelet
aggregation and antagonize vitamin K-dependent clotting factors. Supplemental
vitamin E is not recommended if daily vitamin E intake (including the amount
of vitamin E in Koselugo and supplement) will exceed the recommended or
safe limits due to increased risk of bleeding. An increased risk of bleeding
may occur in patients who are coadministered vitamin-K antagonists or anti-platelet
antagonists with Koselugo. Monitor for bleeding in these patients and increase
international normalized ratio (INR) in patients taking a vitamin-K antagonist.
Perform anticoagulant assessments more frequently and adjust the dose of
vitamin K antagonists or anti-platelet agents as appropriate.
Embryo-Fetal Toxicity. Based on
findings
from animal studies, Koselugo can cause fetal harm when
administered during pregnancy. In animal studies, administration of selumetinib
to mice during organogenesis caused reduced fetal weight, adverse structural
defects, and effects on embryo-fetal survival at approximate exposures
>5 times the human exposure at the clinical dose of 25 mg/m2 twice daily.
Advise patients of reproductive potential of the potential risk to a fetus
and to use effective contraception during treatment with Koselugo and for
1 week after the last dose.
ADVERSE REACTIONS
Common adverse reactions ≥40% include vomiting, rash (all), abdominal pain, diarrhea, nausea, dry skin, musculoskeletal pain, fatigue, pyrexia, acneiform rash, stomatitis, headache, paronychia, and pruritus.
DRUG INTERACTIONS
Effect of Other Drugs on Koselugo
Concomitant use of Koselugo with a strong or moderate CYP3A4 inducer decreased selumetinib plasma concentrations, which may reduce Koselugo efficacy. Avoid concomitant use with Koselugo.
SPECIAL POPULATIONS
Pregnancy & Lactation. Verify the
pregnancy status of patients of reproductive potential prior to
initiating Koselugo. Due to the potential for adverse reactions in a breastfed
child, advise patients not to breastfeed during treatment with Koselugo
and for 1 week after the last dose.
INDICATION
KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca
1-800-236-9933
or at
https://us-aereporting.astrazeneca.com
or FDA at
1-800-FDA-1088 or
www.fda.gov/
medwatch.
Please see full Prescribing Information for Koselugo® (selumetinib).
References:
1. Koselugo. Package insert. AstraZeneca Pharmaceuticals LP.
2. Data on File, REF-75729, AstraZeneca Pharmaceuticals LP.
3. Data on File, REF-37157, AstraZeneca Pharmaceuticals LP.
4. Data on File, REF-37158, AstraZeneca Pharmaceuticals LP.