Moving Beyond Hesitation: Exploring an Oral Option for Managing PNH

Announcer:
Welcome to ReachMD. This medical industry feature, “Moving Beyond Hesitation: Exploring FABHALTA as an Option for Managing PNH,” is sponsored by Novartis Pharmaceuticals Corporation. This program is intended for health care professionals. Here’s your host, Steve Stone, a hematology specialist from Bronson Healthcare in Kalamazoo, Michigan.

Steve Stone:
While enjoying my morning coffee, I reflected on the incredible journey we health care professionals, or HCPs, have been on with our patients diagnosed with paroxysmal nocturnal hemoglobinuria, or PNH. It wasn’t that long ago that patients diagnosed with PNH had limited treatment options1; however, even with more treatment options available, hesitancy to start therapy still exists. 

To further explore this, I spoke with Dr Jamile Shammo, a hematologist at Northwestern Medicine in Chicago, Illinois, with over 20 years of experience. I’ve had many conversations with her in the past and was eager to hear her perspective. Thanks for tuning in!

I’m Steve Stone, and I’m happy to bring you our podcast, “Moving Beyond Hesitation: Exploring FABHALTA as an Option for Managing PNH.” 

In this episode, Dr Shammo and I will explore how we guide our adult patients with PNH and HCPs through early treatment decisions, especially when there is reluctance to start on complement inhibitors.

This podcast is sponsored by Novartis Pharmaceuticals Corporation, and the speakers have been compensated for their time.

Dr Shammo, thank you so much for meeting me here!

Dr Shammo:
Steve, wonderful to see you.

Steve Stone:
I’d like to start with the hesitation of patients on active surveillance regarding the decision to start therapy. Now, I’m not talking about a patient you or I may encounter in an emergency setting, but rather, an adult patient with PNH who is under your care but hasn’t really needed a complement inhibitor. I know I have seen patients with a hemoglobin level of 9.9 g/dL for example, and who reported that their signs and symptoms of PNH were minimally impacting their daily activities.

Dr Shammo:
And would those patients likely be on iron infusions and tolerating the treatment well?

Steve Stone:
Yes. But let’s say their absolute reticulocyte count, or ARC was 139 x 10⁹/L, and their lactate dehydrogenase, or LDH was 400 U/L, which is >1.5 x upper level of normal (ULN).² Additionally if they had a clone size of 25%, I would want to start them on a complement inhibitor because I feel they could be underreporting the impact that PNH may be having on them. But despite their understanding of the benefits of complement inhibitors, some patients may feel their PNH is not severe enough to start this treatment. For these cases, I believe there’s still an unmet need: clear, widely accepted criteria for when to move borderline patients in outpatient clinics beyond supportive iron infusions.^3,4 Dr Shammo, based on your experience, where do you think patient hesitancy to start on a complement inhibitor comes from?

Dr Shammo:
I agree that determination of whether a patient needs treatment beyond iron infusions can be tricky, and I think it relies on assessing a patient’s specific labs.

Regarding patient hesitancy, I get it, complement inhibitors can feel like a big step. Therefore, I try to get to the root cause of that hesitation, which is usually in borderline patients who have previously refused complement inhibitors because their symptoms and occasional iron infusions have allowed them to continue their daily activities with minimal impact. I think the hesitation may partially stem from the fact that once treatment is started, it is a lifelong process.^4,5

Steve Stone:
Interesting. And what else?

Dr Shammo:
I find that the less sick my patients are, the more hesitant they may be to go on intravenous, or IV, therapy. This is when I have a serious conversation with them to discuss available options. We might be able to find the appropriate fit for them per their lifestyle and other personal preferences, and an oral option might be appropriate for them. But I’ll be honest, Steve. In my experience, most patients that come into my office are ready to start treatment by the time I see them. They are at a point where they know enough about the disease and understand why treatment is important.^4,6

Steve Stone:
That’s wonderful, but if you encountered a hesitant patient, how would you guide patients toward an informed decision?

Dr Shammo:
In my clinical practice, I believe in validating my patients’ concerns, but I also try to shift their mindset from “this is scary” to “this is proactive.” It’s a way to stay ahead of the disease.

Steve Stone:
Absolutely. I think one of the biggest challenges is that patients may feel fine right up to the moment when their symptoms suddenly seem worse.⁶

Dr Shammo:
This is why I think making sure patients understand the basics of PNH is key and can be helpful with their willingness to start treatment and long-term compliance for the future. Finally, I also want to understand how the patient has been feeling and how PNH is impacting their day-to-day activities. I want them to understand how a complement inhibitor may help us manage their disease better.^4,6,7-12

Steve Stone:
Talking to my patients about the clinical data of what may be possible can be also helpful. So, in my opinion, once we talk about why they need treatment, we can then talk about how we approach it. That can be a whole visit in and of itself!

Dr Shammo:
Steve, I also want to emphasize that our current discussions with patients who are hesitant to start treatment are quite different from those we had in 2020. Our PNH tool kit today has so many more options. We have clinical data supporting the use of complement inhibitors for both complement inhibitor–naive and complement inhibitor–experienced patients.^7-12 And while the data for complement inhibitors in the naive population are, in some cases, involving single-arm studies and weren’t compared head-to-head, there still exist comprehensive data.^7-11

Steve Stone:
Thank you, Dr Shammo. I always love having these conversations with you. When we return, we will continue discussing the changing PNH landscape and how FABHALTA may be appropriate for adult patients with PNH who are hesitant to start taking a complement inhibitor. Stay tuned!

Announcer:
INDICATION
FABHALTA is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA
FABHALTA, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

• Complete or update vaccinations for encapsulated bacteria at least 2 weeks prior to the first dose of FABHALTA, unless the risks of delaying therapy with FABHALTA outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
• Patients receiving FABHALTA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
  Because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FABHALTA REMS.

CONTRAINDICATIONS

• Patients with serious hypersensitivity to FABHALTA or any of the excipients.
• For initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b.

Steve Stone:
And we’re back! Thank you for that review of the Important Safety Information. Dr Shammo, what about FABHALTA stands out to you?

Dr Shammo:
Well, first is the fact that FABHALTA is the first and only oral monotherapy for adults with PNH.^10,13 It’s one 200-mg capsule that’s taken twice daily,¹⁰ so there’s no need to schedule infusion appointments or travel to infusion centers, which can fit nicely into certain patients’ lifestyles. But I’ll admit, Steve, I was initially concerned about an oral option for such a serious disease.^4,10 It felt like relinquishing control of the disease to the patients themselves. However, my patients who are taking oral treatments, like FABHALTA, seem to be surprisingly compliant. I think being involved in the decision process helps them understand how important compliance is for their situation.^4-6,10,14

Steve Stone:
That’s great! We’ve also had success with patients tracking their oral medication for the first 3 months using calendars. The hope in doing this is to help them establish the habit.

Dr Shammo:
Clever! I also think that as more HCPs use FABHALTA in their clinics and see what it can do for their patients, the more they will embrace it as a treatment option. What also stands out is the mechanism of action of FABHALTA. FABHALTA can control both types of hemolysis comprehensively. It acts proximally in the alternative complement pathway to control both C3b-mediated extravascular hemolysis, or EVH, and terminal complement–mediated intravascular hemolysis, or IVH.¹⁰ FABHALTA has comprehensive data for both C5i-experienced and complement inhibitor–naive patients.¹⁰

Steve Stone:
I believe you’re referring to the phase 3 APPLY trial, for the C5i-experienced patients,¹⁵ correct?

For our listeners, just as a reminder, APPLY was a phase 3, randomized, open-label, active comparator–controlled trial to assess the efficacy and safety of switching to FABHALTA compared with continuing on intravenous C5i therapy for the 24-week randomized treatment period followed by a 24-week treatment extension period. The study included US-approved and non–US-approved eculizumab or ravulizumab in adult patients with PNH and residual anemia, defined as a mean hemoglobin <10 g/dL despite previous treatment with a stable regimen of C5i treatment for at least 6 months.^10,15,16 In total, 97 patients were randomized in an 8:5 ratio to either switch to FABHALTA 200 mg orally twice daily or continue their C5i regimen¹⁵; 62 were randomized to the FABHALTA arm; 35 were randomized to the comparator arm, of which 23 patients were on eculizumab, and 12 patients were on ravulizumab.¹⁵

Dr Shammo:
Yes, and the primary end points were the proportion of patients achieving a hemoglobin increase of ≥2 g/dL and the proportion of patients achieving a hemoglobin level of ≥12 g/dL, both without the need for RBC transfusions.¹⁵ What we learned is that more patients achieved hemoglobin improvements in the absence of RBC transfusions with FABHALTA vs C5is.¹⁵ The response rate for increasing hemoglobin levels at least 2 g/dL from baseline and in the absence of RBC transfusions was 82.3% in patients who switched to FABHALTA vs 0% for patients who continued on C5i therapy.¹⁰

In addition, the response rate for hemoglobin levels ≥12 g/dL in the absence of RBC transfusions (the additional end point for APPLY) was 67.7% for those who switched to FABHALTA vs 0% for patients who continued on C5is.^10,15 I like to refer to this as “normalization of hemoglobin levels” because, although normal hemoglobin levels may vary, they’re generally between 12-16 g/dL for women and 13-18 g/dL for men.^17,18

Steve Stone:
I think these are comprehensive results. And what can you tell our audience about the safety of FABHALTA in these patients?

Dr Shammo:
During the 24-week randomized treatment period of APPLY, the adverse reactions reported in >5% of adults with PNH treated with FABHALTA vs C5is were, respectively: headache in 19% vs 3% of patients, nasopharyngitis in 16% vs 17% of patients, diarrhea in 15% vs 6% of patients, abdominal pain in 15% vs 3% of patients, bacterial infection in 11% vs 11% of patients, nausea in 10% vs 3% of patients, viral infection in 10% vs 31% of patients, arthralgia in 8% vs 3% of patients, and thrombocytopenia, dizziness, systemic hypertension, and lipid disorder in 6% vs 0% of patients.¹⁰ No patients discontinued FABHALTA or C5is due to an adverse reaction during the 24-week randomized treatment period.¹⁵ Serious adverse reactions were reported in 2 out of 62 adult patients with PNH treated with FABHALTA (3%) and included pyelonephritis, urinary tract infection, and coronavirus disease 2019, or COVID-19.¹⁰

Steve Stone:
So, this study gave you the confidence that FABHALTA is effective in patients with suboptimal response to C5is?

Dr Shammo:
Exactly. And this is the scenario I see the most in my clinical practice at Northwestern Medicine.

Steve Stone:
That raises the next question: Would you consider using FABHALTA for complement inhibitor–naive patients with PNH who are reluctant to start a complement inhibitor due to minimal symptoms?

Dr Shammo:
Personally, Steve, I don’t have direct experience using FABHALTA in a scenario like that, but I would consider it if I did. To me, the APPOINT data really do indicate that FABHALTA can be an appropriate option for those patients.

APPOINT was a phase 3, open-label study with a single arm and no comparator control. It was designed to assess the efficacy and safety of FABHALTA 200 mg orally twice daily during the 24-week core treatment period in adult patients (N=40) who were complement inhibitor–naive, diagnosed with PNH, had a mean hemoglobin <10 g/dL, and had an LDH level >1.5 times the upper limit of normal.^2,10

Steve Stone:
Yes, and APPOINT shared one of the primary end points with APPLY, which was the proportion of patients achieving sustained hemoglobin increases of ≥2 g/dL from baseline without a need for RBC transfusions.¹⁵

In APPOINT, we saw that the majority of complement inhibitor–naive adults also experienced hemoglobin improvements of ≥2 g/dL from baseline in the absence of RBC transfusions. Based on central labs, the response rate was 77.5%. But in a sensitivity analysis where local labs were included when central labs weren’t available, the response rate was 87.5%.¹⁰

Dr Shammo:
Correct. We see that in APPOINT, patients with a hemoglobin below 10 g/dL and high LDH responded well to FABHALTA, with a majority of patients demonstrating a response rate (eg, control of hemolysis and hemoglobin normalization).^10,15,19 There is no doubt in my mind that these data are comprehensive. Also, during the 24-week core treatment period, there were no clinical breakthrough hemolysis events, but this is something we always need to monitor.^10,15

Steve Stone:
Agreed.

Dr Shammo:
I think it’s also important to consider the safety results for APPOINT. Adverse reactions reported in >5% of patients in the 24-week core treatment period included headache in 28% of patients; viral infection in 18% of patients; nasopharyngitis in 15% of patients; rash in 10% of patients; as well as abdominal pain, diarrhea, and lipid disorder in 8% of patients.¹⁰ Bacterial infection and nausea were each reported in 2 patients (5%), and dizziness and urticaria were each reported in 1 patient (3%).¹⁰ Serious adverse reactions were reported in 2 out of 40 patients (5%) and included COVID-19 and bacterial pneumonia.¹⁰ No patient discontinued FABHALTA due to an adverse reaction in the core treatment period of APPOINT.^10,15

In adults with PNH across the APPLY and APPOINT studies, the most common adverse reactions (≥10%) with FABHALTA were headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, viral infection, nausea, and rash.¹⁰

Steve Stone:
That’s good to know. And while we’re on the topic of safety, I’d also like to note that because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is only available through a Risk Evaluation and Mitigation Strategy (REMS) program that requires vaccinations.¹⁰

Next, we’ll hear additional Important Safety Information about serious infections caused by encapsulated bacteria, and our listeners should continue listening to this podcast in its entirety to hear the full Important Safety Information, including the Indication and Boxed WARNING, and visit www.fabhalta-hcp.com/pnh for more information.

Announcer:
WARNINGS AND PRECAUTIONS
Serious Infections Caused by Encapsulated Bacteria

• FABHALTA, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including nongroupable strains), and Haemophilus influenzae type b. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of FABHALTA is contraindicated in patients with unresolved serious infections caused by encapsulated bacteria.
• Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to the start of FABHALTA, according to the current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with FABHALTA. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent FABHALTA therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with FABHALTA, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria.
  
• Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if they occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of FABHALTA in patients who are undergoing treatment for serious infections, depending on the risks of interrupting treatment in the disease being treated.

Steve Stone:
And we’re back. Dr Shammo, what are your thoughts on FABHALTA and your experience with using it?

Dr Shammo:
Well, as I mentioned previously, I have had experience using FABHALTA in switch patients. So, I would recommend FABHALTA for appropriate switch patients, but I would like to emphasize, as I did before, that this is a shared decision made between patients and their HCPs. I think hemoglobin normalization in patients can be impactful. I have seen firsthand how my patients have got into the normal hemoglobin range^15,17,18 and how excited they felt. I think because PNH is so rare,⁴ the patients who walk into my office tend to be well educated on their disease. I also make sure to review and discuss their lab results. So, for the patients who see their hemoglobin levels improve and normalize, they understand the implications of that.

Steve Stone:
I agree. Happy to share that I also currently have a patient on FABHALTA who is doing well and no longer dealing with his injection site issues or his ongoing anemia due to EVH. His hemoglobin is normal, and he has no ongoing hemolysis. Results vary from patient to patient. What about patients who are complement inhibitor–naive? When would you consider FABHALTA being appropriate?

Dr Shammo:
I think it is important to see what the patient’s hemoglobin, LDH values, and clone size are before starting treatment.^1,20

I would also want to know whether the patient was transfusion dependent or required anticoagulation to treat prior blood clots. I think these are important factors that give an HCP an idea of the severity of the disease.^19,20

Finally, I believe FABHALTA can be an option for appropriate patients¹⁰ who recognize the importance of adherence to this oral treatment that may fit their day-to-day lifestyle and after discussing all options. Also, by prescribing FABHALTA to patients with a similar profile as those in the APPOINT clinical trial, we can ensure the appropriateness of FABHALTA for the complement inhibitor–naive individuals who may benefit from this treatment.

Steve Stone:
Thanks again, Dr Shammo, for sharing your time and wisdom with us! Any final thoughts?

Dr Shammo:
Steve, my pleasure!

I believe there’s so much more that goes into considering FABHALTA for adult patients with PNH than what was discussed today. I encourage our listeners today to dive into the clinical data supporting FABHALTA use, including breakthrough hemolysis, major adverse vascular events, and longer-term data at www.fabhalta-hcp.com/pnh.

Overall, I think we’ve come a long way and have a better grasp on how to offer patients the appropriate therapy that meets their specific needs.

Narrator:
Thank you for tuning into the “Moving Beyond Hesitation: Exploring FABHALTA as an Option for Managing PNH” podcast!

Please continue listening to hear the full Important Safety Information for FABHALTA, including the indication and Boxed WARNING. More details are available in the full Prescribing Information, including the Boxed WARNING and Medication Guide, via the link on this site or at www.fabhalta-hcp.com/pnh.

Announcer:
INDICATION
FABHALTA is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA

FABHALTA, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.
Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

• Complete or update vaccinations for encapsulated bacteria at least 2 weeks prior to the first dose of FABHALTA, unless the risks of delaying therapy with FABHALTA outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
• Patients receiving FABHALTA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
  Because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FABHALTA REMS.

CONTRAINDICATIONS

• Patients with serious hypersensitivity to FABHALTA or any of the excipients.
  
• For initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b.

WARNINGS AND PRECAUTIONS
Serious Infections Caused by Encapsulated Bacteria

• FABHALTA, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including nongroupable strains), and Haemophilus influenzae type b. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of FABHALTA is contraindicated in patients with unresolved serious infections caused by encapsulated bacteria.
• Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to the start of FABHALTA, according to the current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with FABHALTA. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent FABHALTA therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with FABHALTA, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria.
• Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if they occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of FABHALTA in patients who are undergoing treatment for serious infections, depending on the risks of interrupting treatment in the disease being treated.

FABHALTA REMS

• FABHALTA is available only through a restricted program under a REMS called FABHALTA REMS, because of the risk of serious infections caused by encapsulated bacteria.
• Under the FABHALTA REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card during treatment and for 2 weeks following last dose of FABHALTA.
• Further information is available by telephone: 1-833-993-2242 or online at www.FABHALTA-REMS.com.

Monitoring of PNH Manifestations After FABHALTA Discontinuation

• After discontinuing FABHALTA, closely monitor patients for at least 2 weeks after the last dose for signs and symptoms of hemolysis. These signs include elevated lactate dehydrogenase (LDH) levels along with sudden decrease in hemoglobin or PNH clone size, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (such as thrombosis, stroke, and myocardial infarction), dysphagia, or erectile dysfunction. If discontinuation of FABHALTA is necessary, consider alternative therapy.
• If hemolysis occurs after discontinuation of FABHALTA, consider restarting treatment with FABHALTA, if appropriate, or initiating another treatment for PNH.

Hyperlipidemia

• FABHALTA may increase total cholesterol, LDL cholesterol, and serum triglycerides.
• Of 88 FABHALTA-treated patients who had normal total cholesterol at baseline, 31 developed grade 1 hypercholesterolemia during the randomization or core treatment period and 1 patient worsened from baseline grade 1 to grade 2.
• Of 96 FABHALTA-treated patients with LDL cholesterol ≤ 130 mg/dL at baseline during the randomization or core treatment period, 14 patients developed LDL cholesterol > 130-160 mg/dL, 6 patients developed LDL cholesterol > 160-190 mg/dL and 4 patients developed LDL cholesterol > 190 mg/dL.
• Of 89 FABHALTA-treated patients with normal triglycerides during the randomization or core treatment period, 22 patients developed grade 1 elevated triglycerides. Three patients experienced an increase in triglycerides from grade 1 to grade 2.
• Of the 102 FABHALTA-treated patients in APPLY-PNH and APPOINT-PNH, 2 patients required cholesterol-lowering medications.
• Monitor serum lipid parameters periodically during treatment with FABHALTA and initiate cholesterol-lowering medications, if indicated.

ADVERSE REACTIONS

• The most common adverse reactions (≥10%) in adults with PNH receiving FABHALTA were headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, viral infection, nausea, and rash.

DRUG INTERACTIONS

• Concomitant use of CYP2C8 inducers (eg, rifampin) may decrease iptacopan exposure, which may result in loss of or reduced efficacy of FABHALTA. Monitor the clinical response and discontinue use of the CYP2C8 inducer if loss of efficacy of FABHALTA is evident.
• Concomitant use of strong CYP2C8 inhibitors (eg, gemfibrozil) may increase iptacopan exposure, which may result in increased risk for adverse reactions with FABHALTA. Coadministration with a strong CYP2C8 inhibitor is not recommended.

USE IN SPECIFIC POPULATIONS

• Because of the potential for serious adverse reactions in a breastfed child, breastfeeding should be discontinued during treatment and for 5 days after the final dose.
• FABHALTA is not recommended in patients with severe hepatic impairment (Child-Pugh class C). No dose adjustment is required for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Boxed WARNING and Medication Guide.

Announcer:
This program was sponsored by Novartis Pharmaceuticals Corporation. If you missed any part of this discussion, visit https://reachmd.com/industry-feature. This is ReachMD. Be part of the knowledge.

References:

1. Kulasekararaj AG, Kuter DJ, Griffin M, Weitz IC, Röth A. Biomarkers and laboratory assessments for monitoring the treatment of patients with paroxysmal nocturnal hemoglobinuria: differences between terminal and proximal complement inhibition. Blood Rev. 2023;59:101041. doi:10.1016/j.blre.2023.101041
2. Data on file. Study CLNP023C12301 CSR. Novartis Pharmaceuticals Corp; 2022.
3. Babushok DV. When does a PNH clone have clinical significance? Hematology Am Soc Hematol Educ Program. 2021;143-152. doi:10.1182/hematology.2021000245
4. Waheed A, Shammo J, Dingli D. Paroxysmal nocturnal hemoglobinuria: review of the patient experience and treatment landscape. Blood Rev. 2024;64:101158. doi:10.1016/j.blre.2023.101158
5. Colden MA, Kumar S, Munkhbileg B, Babushok DV. Insights Into the emergence of paroxysmal nocturnal hemoglobinuria. Front Immunol. 2022;12:830172. doi:10.3389/fimmu.2021.830172
6. Kulasekararaj AG, Brodsky RA, Nishimura J, Patriquin CJ, Schrezenmeier H. The importance of terminal complement inhibition in paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2022;13:20406207221091046. doi:10.1177/20406207221091046
7. Soliris. Prescribing information. Alexion Pharmaceuticals, Inc.
8. Ultomiris. Prescribing information. Alexion Pharmaceuticals, Inc.
9. Empaveli. Prescribing information. Apellis Pharmaceuticals, Inc.
10. Fabhalta. Prescribing information. Novartis Pharmaceuticals Corp.
11. PiaSky. Prescribing information. Genentech, Inc.
12. Voydeya. Prescribing information. Alexion Pharmaceuticals, Inc.
13. de Castro CM, Patel BJ. Iptacopan for the treatment of paroxysmal nocturnal hemoglobinuria. Expert Opin Pharmacother. 2024;25(18):2331-2339. doi:10.1080/14656566.2024.2404110
14. Oliver M, Patriquin CJ. Paroxysmal nocturnal hemoglobinuria: current management, unmet needs, and recommendations. J Blood Med. 2023;14:613-628. doi:10.2147/JBM.S431493
15. Peffault de Latour R, Röth A, Kulasekararaj AG, et al. Oral iptacopan monotherapy in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2024;390(11):994-1008. doi:10.1056/NEJMoa2308695
16. Data on file. Study CLNP023C12302 CSR. Novartis Pharmaceuticals Corp; 2022.
17. Billett HH. Hemoglobin and hematocrit. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Butterworth Publishers; 1990:718-719.
18. Cappellini MD, Motta I. Anemia in clinical practice—definition and classification: does hemoglobin change with aging? Semin Hematol. 2015;52(4):261-269. doi:10.1053/j.seminhematol.2015.07.006
19. Cançado RD, Araújo ADS, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341-348. doi:10.1016/j.htct.2020.06.006
20. Panse JP, Höchsmann B, Schubert J. Paroxysmal nocturnal hemoglobinuria, pathophysiology, diagnostics, and treatment. Transfus Med Hemother. 2024;51(5):310-320. doi:10.1159/000540474

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