Expanding Treatment Options in PNH: Expert Approaches to Personalized Care

Dr Piatek:
When treating my patients with PNH, I’ve always known you have to dig deeper and ask specific questions to uncover how they are truly doing

Years ago, when there were limited treatment options for PNH, my main priorities were keeping hemoglobin levels stable and improving LDH levels.^1,2,23 However, for some patients, despite treatment with C5 inhibitors, they still haveresidual anemia^16,24

Now with more treatment options available to me, I have the opportunity to evaluate and assessa wider variety of therapiesfor my patients

Dr Patel:
For the past decade, my training and career have largely focused on PNH management, primarily using C5 inhibitors.

Given the limited options available at the time, I, along with many other HCPs, believed we were adequately managing their condition.

Dr Piatek:
Residual anemia is one of the most common challenges I see in my patients with PNH, often impacting their everyday activities.^1,2 Some may not fully recognize their limitations because they've adapted their lives around the disease.

I’ve found it challenging to assess patients solely based on hemoglobin levels since I have some patients whose hemoglobin level is outside of the range we typically associate with distinct symptoms. So, pinpointing the cause of any remaining symptoms can be difficult.^1,14,16,24

Dr Patel:
Yes, the labs can say one thing, but the patient can say another.

One of my patients, a nurse in her 30s, was still struggling while on a previous treatment. Her infusions didn't fit her schedule, and her PNH symptoms continued to impact her day-to-day.^2,23,24

Knowing this, I wanted to aim for arefined approach while considering her daily needs. So, it’s very important to listen and really understand what the patient is going through

Dr Piatek:
That’s a great example. I have my patient who, despite being compliant with his treatment, still had some signs of ongoing hemolysis. And after hearing how PNH was affecting his day-to-day, it reminded me how important it is to look beyond each patient’s lab values.²⁴

Dr Patel:
If a patient isn't responding well to their current treatment—maybe their EVH is worsening, they need more transfusions, or PNH continues to impact their day-to-day—I typically start a conversation about exploring other therapy options.^1,2,15,23

Now, with the emergence of therapies like FABHALTA, which delivers comprehensive control of IVH and EVH, I now have another treatment option to offer to my eligible adult patients with PNH³.

Dr Piatek:
For me, the variety of therapy options highlights that managing patients with PNH is never a “one-size-fits-all” approach.

Dr Patel:
Among the options, FABHALTA is one of the treatment choices for PNH.³ Now I know we're all eager to see the data for FABHALTA, but first, let's take a moment to review the indication and Important Safety Information for FABHALTA.

Voiceover:
INDICATION
FABHALTA^® (iptacopan) 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.

Dr Patel:
FABHALTA has been studied in a total of 4 clinical trials including 3 different populations of patients with PNH.^3-6 In this video, we will only focus on the APPLY study and the APPULSE study.

Dr Piatek:
The APPLY study was a phase 3, open-label, head-to-head trial of FABHALTA vs C5 inhibitors in C5 inhibitor–experienced patients with PNH switching from eculizumab or ravulizumab.^3,8

The study evaluated the efficacy and safety of switching to FABHALTA in adults with PNH and residual anemia, defined as a mean hemoglobin less than 10 g/dL, despite previous and stable C5 inhibitor treatment with either eculizumab or ravulizumab for at least 6 months.^3,8

Patients enrolled were at least 18 years of age, had red blood cell and white blood cell clone size greater than or equal to 10%, and absolute reticulocyte count greater than or equal to 100 x 109/L.^3,8

After the screening period, 97 patients either switched to FABHALTA 200 mg twice daily or continued their existing intravenous C5 inhibitor regimen during the 24-week randomized treatment period.^3,8

The randomized treatment period was followed by a 24-week treatment extension period where patients on FABHALTA continued treatment and patients on C5 inhibitors switched to FABHALTA.³ In APPLY, FABHALTA was assessed against C5 inhibitors, eculizumab and ravulizumab. I find this direct comparison can give clinicians the evidence they need to confidently incorporate FABHALTA into their PNH treatment plans.³

Actually, the APPLY study was the first study in PNH to evaluate sustained hemoglobin increase of greater than or equal to 2 g/dL as a primary end point instead of hemoglobin stabilization.^3,18,21,22

The primary end points in the randomized period of APPLY were the proportion of patients achieving a hemoglobin increase of greater than or equal to 2 g/dL and the proportion of patients achieving a hemoglobin level of greater than or equal to 12 g/dL, both without the need for red blood cell transfusions.³

Additional end points included.^3,25 Red blood cell transfusion avoidance, change from baseline in hemoglobin levels, FACIT-Fatigue scores, absolute reticulocyte count, and LDH levels; occurrence of major adverse vascular events; clinical breakthrough hemolysis; and safety.

I’ve noticed there are studies on using proximal inhibitors in complement inhibitor–naive and C5 inhibitor–experienced patients with significant EVH, but what about another patient population, those who have a hemoglobin level greater than or equal to 10 g/dL taking eculizumab or ravulizumab?^3,18

That's why I believe the APPULSE study is valuable, as it helps us learn more about switching patients who have been on a stable C5 inhibitor regimen of either eculizumab or ravulizumab.^3,4

Dr Patel:
Agreed. The APPULSE study not onlycaptures a distinct patient group with PNH, but it can broaden our understanding of the role of FABHALTA in PNH treatment across different types of patients with PNH.^3,4I believe the APPULSE study is one of the reminders of Novartis' dedication to understanding what FABHALTA may offer to the PNH community.⁴

The APPULSE study explored adults with PNH and a hemoglobin level greater than or equal to 10 g/dL over a period of 6 months before the screening visit who switched to FABHALTA from a stable C5 inhibitor regimen of eculizumab or ravulizumab for at least 6 months.⁴ APPULSE was a phase 3b multicenter, single-arm, open-label study that evaluated the efficacy and safety of FABHALTA in adults with PNH who switched from C5 inhibitors (eculizumab or ravulizumab).⁴

Patients enrolled were at least 18 years of age, had a PNH white blood cell clone size greater than or equal to 10%, were required to be on a stable regimen with C5 inhibitors (eculizumab or ravulizumab) for at least 6 months prior to screening with a mean hemoglobin level of greater than or equal to 10 g/dL, had no red blood cell transfusions in this period, and had absolute reticulocyte count greater than or equal to 100 x 109/L.⁴

Following an 8-week screening to confirm eligibility, including transfusion history, 52 patients switched to FABHALTA 200 mg twice daily during the 24-week treatment period.^4,11

The primary end point was the adjusted mean change from baseline in hemoglobin levels after 24 weeks of treatment with FABHALTA following the switch from a C5 inhibitor.

Additional end points included.⁴ Proportion of patients achieving hemoglobin level of greater than or equal to 12 g/dL without the need for red blood cell transfusions, red blood cell transfusion avoidance, FACIT-Fatigue scores, absolute reticulocyte count, and LDH levels; occurrence of major adverse vascular events; clinical breakthrough hemolysis; and safety.

Dr Piatek:
It's key to remember that the APPLY study is the pivotal trial that led to the FDA approval of FABHALTA for treating adults with PNH.

The APPULSE study is an additional study that provides further evidence for the clinical profile of FABHALTA and its role in the treatment landscape for PNH.^3,4,8,12,13

Dr Patel:
Agreed. When I review data from both APPLY and APPULSE studies, I keep in mind that the comparator group in APPLY and all patients in APPULSE were on a stable C5 inhibitor treatment with either eculizumab or ravulizumab for at least 6 months.^3,4

Dr Piatek:
Definitely. In APPLY, the mean therapy time on prior C5 inhibitors was 3.8 years in the FABHALTA treatment arm and 4.2 years in the C5 inhibitor treatment arm. Both treatment arms had the same mean hemoglobin level of 8.9 g/dL at baseline.^3,8

Additionally, 56.5% of patients in the FABHALTA treatment arm and 60% of those in the C5 inhibitor treatment arm received 1 or more red blood cell transfusions in the 6 months prior to randomization.³

Baseline characteristics, such as mean absolute reticulocyte count, indicated that some patients enrolled in the APPULSE study may have been experiencing ongoing signs and symptoms of PNH.^2,4,14,26

In APPULSE, the mean time on prior C5 inhibitors was 3.5 years and the mean hemoglobin level was 11.87 g/dL at baseline.⁴ The mean LDH value was 226.8 U/L and mean absolute reticulocyte count was 154.84 x 109/L for patients entering APPULSE.⁴

Dr Patel:
The APPULSE baseline characteristics are consistent with my expectations for this patient group.

Dr Piatek:
Because absolute reticulocyte count is a marker of both EVH and IVH, the mean absolute reticulocyte count seen in patients in both studies suggests possible hemolysis was still occurring. In my personal experience, this is something I would look for when assessing a patient’s therapy.^4,8,14,26

IMPORTANT SAFETY INFORMATION (continued)

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.

Dr Patel:
Understanding the impact of FABHALTA on hemoglobin levels is essential for me since hemoglobin management is a key focus in my practice for C5 inhibitor–experienced patients with PNH.³

I see hemoglobin improvement as a key indicator of disease control, which ultimately translates to improved PNH symptom management for patients.^14,15 That's why I think a hemoglobin increase of 2 g/dL or more is important.

In my practice, my aim isn't to achieve a “perfect” hemoglobin number, but rather to see meaningful improvement that's reflected in the patient’s symptomatology.^14,15 It's about improving the patient as a whole, not just hitting a target

Dr Piatek:
That’s true. I think hemoglobin normalization is a growing topic in PNH treatment. While normal hemoglobin levels vary, generally 12 to 16 g/dL for women and 13 to 18 g/dL for men, aiming for at least 12 g/dL seems reasonable given gender differences.^16,17

Dr Patel:
Given that FABHALTA can offer comprehensive hemolysis control of EVH and IVH, I would expect to see a change in hemoglobin levels, although the magnitude of the change remains uncertain.³

Dr Piatek:
This was seen in the APPLY study, where FABHALTA demonstrated superior hemoglobin improvements in the absence of red blood cell transfusions over C5 inhibitors during the 24-week randomized treatment period.³ 82.3% of patients on FABHALTA achieved a hemoglobin increase of greater than or equal to 2 g/dL from baseline in the absence of red blood cell transfusions compared with 0% in patients on C5 inhibitors.³

Hemoglobin levels of 12 g/dL or higher without red blood cell transfusions after 24 weeks were achieved in 67.7% of patients on FABHALTA compared with 0% of patients on C5 inhibitors.³

Dr Patel:
I agree. In my experience, FABHALTA has shown hemoglobin increases across different types of patients with PNH.^3,12 To me, the hemoglobin improvements from APPLY are clinically meaningful for my practice and help support the results seen in APPULSE.

Dr Piatek:
Definitely, since patients with low hemoglobin may need regular blood transfusions.¹⁴

Dr Patel:
Any hemoglobin improvement is a positive step toward achieving transfusion avoidance in our patients. It’s great to know that we have data showing hemoglobin changes in patients taking FABHALTA.¹⁴

Dr Piatek:
You make a great point. In fact, the APPLY study showed that almost all patients taking FABHALTA remained free from red blood cell transfusions through the 24-week randomized treatment period.³

Assessed between Weeks 2 and 24, the transfusion avoidance response rate was 95.2% for patients on FABHALTA compared with 45.7% for patients on C5 inhibitors.³ That is a difference of 49.5%.³

Dr Patel:
Change in hemoglobin levels was seen in the APPULSE study, as patients experienced an adjusted mean change from baseline of plus 2.07 g/dL after switching from a stable C5 inhibitor regimen of eculizumab or ravulizumab.¹²

Although we cannot make any formal conclusions from the data, I believe these data are a valuable addition to our toolkit for informed treatment discussions with patients. Regardless of what was anticipated, these data can facilitate deeper shared decision-making.

Additionally, in APPULSE, all patients receiving FABHALTA remained transfusion-free through the 24-week treatment period after switching from eculizumab or ravulizumab.^4,12 It's encouraging to see that patients in APPULSE were 100% transfusion avoidant with FABHALTA, as transfusions can present their own set of complications.¹²

Dr Piatek:
With all the data and its alignment with what I’ve seen in my practice, I feel confident saying that FABHALTA is an option for appropriate C5 inhibitor–experienced adult patients with PNH.

Ultimately, as health care professionals, we want to ensure that any PNH therapy we choose continues to address key measures of the disease like hemoglobin levels and the need for red blood cell transfusions.¹⁴

Dr Patel:
I think FABHALTA, as an oral monotherapy, has the potential to be an attractive alternative for some patients on a C5 inhibitor, regardless of their hemoglobin levels.^3,27

Dr Piatek:
That’s true, but it’s important to remember that compliance is a key factor. When talking to my patients about FABHALTA, I ask them to honestly consider whether they can manage a twice-daily oral medication.^3,28 As long as my patients understand the importance of adherence, I'm committed to equipping them with the tools they need to prioritize staying on their PNH medication.

Dr Patel:
While patients taking FABHALTA experienced a hemoglobin increase in both studies,it's crucial to remember that safety should remain a key consideration when choosing a PNH therapy.^3,12

Dr Piatek:
Absolutely. I believe close monitoring is crucial in patients receiving therapy, not only to assess treatment response, but to ensure patient safety.¹⁴

In APPLY, the adverse reactions reported in greater than 5% of adults with PNH treated with FABHALTA vs C5 inhibitors 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.³

In APPLY, it is important to note that serious adverse reactions of pyelonephritis, urinary tract infection, and COVID-19 were reported in 2 patients taking FABHALTA.³ Rash was reported in 2 patients, or 3%, on FABHALTA.³

Of the 37 FABHALTA-treated patients who had normal platelet counts at baseline, 43% experienced any-grade thrombocytopenia during the randomized treatment period.³

Three FABHALTA-treated patients experienced decreased platelets that worsened to greater than or equal to grade 3 from baseline, including 1 patient with normal platelets that worsened to grade 4, 1 patient with grade 1 that worsened to grade 4, and 1 patient with grade 3 that worsened to grade 43.

It’s important to note that no patient discontinued FABHALTA or C5 inhibitors due to an adverse reaction during the 24-week randomized treatment period of APPLY. One patient discontinued FABHALTA due to pregnancy.⁸

Dr Patel:
It's important to acknowledge that the APPULSE study data are for observation only, and no formal conclusions can be made.
In APPULSE, adverse reactions reported in greater than 5% of adults taking FABHALTA included headache in 17.3% of patients, nasopharyngitis in 17.3% of patients, viral infection in 13.5% of patients, diarrhea in 11.5% of patients, nausea in 11.5% of patients, bacterial infection in 9.6% of patients, lipid disorder in 7.7% of patients, and thrombocytopenia in 5.8% of patients during the 24-week treatment period.^4,11

To me, in addition to regular safety assessments like lab monitoring and symptom evaluation, vigilant observation for serious adverse events is essential for optimizing a therapy's benefit-risk profile.

As a reminder, the APPULSE study data are for observation only.So, no formal conclusions can be made. During the 24-week treatment period, a serious adverse reaction of bacterial pneumonia was reported in 1 patient.^4,11 One patient discontinued FABHALTA treatment due to an adverse reaction of intermittent heart palpitations.^4,11

Dr Piatek:
Other outcomes to monitor for in patients with PNH on complement-inhibitor therapy include breakthrough hemolysis, or BTH, and major adverse vascular events, or MAVEs, which were measured in both APPLY and APPULSE studies.^4,8

It’s important to note that both BTH and major adverse vascular events data in the APPLY study are descriptive in nature, presented for observation only. No formal conclusions or comparisons between the 2 treatment arms can be made. Additionally, for BTH data, the planned power for the hypothesis testing was low.

During the 24-week randomized treatment period in APPLY, the annualized rate of clinical BTH was 0.07 for patients treated with FABHALTA and 0.67 for patients treated with C5 inhibitors.⁸

Additionally, there was no statistically significant difference in the annualized rates of major adverse vascular events between FABHALTA and C5 inhibitors during the APPLY 24-week randomized treatment period.⁸

In APPLY, 1 patient experienced transient ischemic attack in the FABHALTA treatment arm, which was deemed unrelated to treatment by the investigator, and 0 out of 35 patients experienced a major adverse vascular event in the C5 inhibitor treatment arm.⁸

Dr Patel:
How interesting! To help prevent breakthrough hemolysis in my practice, a key part of my strategy involves educating patients to recognize worsening symptoms and empowering them to immediately inform me of any potential infectious complications.^29,30

In APPULSE, the data are for observation only. No formal conclusions can be made. However, it’s worth noting that during the 24-week treatment period, no clinical breakthrough hemolysis or major adverse vascular events were observed in patients on FABHALTA.⁴

Dr Piatek:
Breakthrough hemolysis is a serious concern, so I focus on preparing my patients to be active partners in their care by educating them about potential triggers like surgery or infection that can increase their risk of breakthrough hemolysis.^29,30

I prioritize monitoring monitoring my patients closely for major adverse vascular events.

Dr Patel:
I agree. Overall, the results from APPULSE provide additional information regarding the safety profile of FABHALTA.^4,11

As a reminder, the most common adverse reactions of 10% or greater in adults with PNH receiving FABHALTA were headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, viral infection, nausea, and rash.³

Lastly, it’s important to note that because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is only available through a restricted program under a REMS called FABHALTA REMS.³

So, even after my patient and I have determined that FABHALTA is the right choice, I still need to fulfill the requirements of the FABHALTA REMS to start them on their FABHALTA journey.³

The next step is to vaccinate my patients at least 2 weeks before starting treatment and updating as required by the ACIP guidelines. Vaccination against encapsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae, is required.³

If urgent FABHALTA therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.³

The last step is choosing between 2 specialty pharmacies certified under the REMS program to dispense FABHALTA medication.³

Dr Piatek:
Thanks for sharing your insights, Dr Patel. Surely, we can agree that APPLY and APPULSE provides further data supporting the use of FABHALTA in the treatment of patients with PNH switching from eculizumab or ravulizumab.^3,4

These data are so important to include in our shared decision-making discussions with our patients.

Dr Patel:
I've truly enjoyed ourconversation. With the addition of the data from APPULSE, the evidence supporting the use of FABHALTA across a broader spectrum of patients with PNH continues to grow.^3,4

FABHALTA is the first and only oral monotherapy that iscapable of increasing hemoglobin levels with comprehensive hemolysis control of IVH and EVH.^3,18-22That’s potentially practice-changing!

Dr Piatek:
Absolutely. Thank you so much. Continue watching for the full indication and Important Safety Information

Voiceover:
INDICATION
FABHALTA^® (iptacopan) is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

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 APPOINTPNH, 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.

References:

1. Cañçado 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
2. Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: current treatments and unmet needs. J Manag Care Spec Pharm. 2020;26(12-b suppl):S14-S20. doi:10.18553/jmcp.2020.26.12-b.s14
3. Fabhalta (iptacopan) [prescribing information]. Novartis Pharmaceuticals Corp.
4. Novartis Pharmaceuticals Corp. Study CLNP023C12303 CSR. Data on file; 2024.
5. Novartis Pharmaceuticals Corp. Study CLNP023C12001B supporting analyses using 2-year efficacy data for US medical deck. Data on file; 2025.
6. Novartis Pharmaceuticals Corp. Study CLNP023C12001B supporting analyses using 2-year safety data for US medical deck. Data on file; 2025.
7. Novartis. Novartis receives FDA approval for FABHALTA® (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH. Published December 6, 2023. Accessed June 30, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh
8. Novartis Pharmaceuticals Corp. Study CLNP023C12302 CSR. Data on file; 2022.
9. Novartis Pharmaceuticals Corp. Phase III APPLY-PNH and APPOINT-PNH trials. Data on file; 2023.
10. Novartis Pharmaceuticals Corp. Study CLNP023C12301 and Study CLNP023C12302 supporting analyses for USPI clinical efficacy section. Data on file; 2023.
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