ADYNOVATE® [Antihemophilic Factor (Recombinant), PEGylated] Indications and Limitations of use. ADYNOVATE is a human antihemophilic factor indicated in children and adults with hemophilia A, congenital factor VIII deficiency for on-demand treatment and control of bleeding episodes, perioperative management, routine prophylaxis to reduce the frequency of bleeding episodes. ADYNOVATE is not indicated for the treatment of von Willebrand disease.
Detailed Important Risk Information.
Contraindications: Prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE [Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE, for example Tris, mannitol, trehalose, glutathione, and/or polysorbate 80.
Hello, my name is Dr. Ayesha Zia, and today I’m here to talk to you about patients with hemophilia A. It’s important to remember that every patient is different, but today I’d like to consider a particular group of patients: patients who are looking to stay the course.
By that, I mean patients who are on a prophylactic regimen that is currently working for them. These patients are comfortable with their current level of bleed control, able to adhere to their current regimen, and reluctant to make a switch in their treatment.
In my practice, some of these patients who want to “stay the course” are treated with ADYNOVATE.
- Proven bleed protection
- And a simple, twice-weekly dosing schedule given on the same two days every week
For these reasons, continuing treatment with ADYNOVATE is a consideration, especially for my patients who are responding well and looking to "stay the course."
Let’s review the clinical data and real-world experience supporting the use of ADYNOVATE for prophylaxis.
A clinical study was performed to assess the efficacy, PK, and safety of ADYNOVATE twice-weekly prophylaxis compared with on-demand treatment.
137 previously treated male patients aged 12 years and older with severe hemophilia A underwent 6 months of either prophylactic treatment or on-demand treatment with ADYNOVATE.
In this clinical study, ADYNOVATE demonstrated the ability to help patients prevent bleeding episodes using a prophylaxis regimen, with a low median overall annualized bleeding rate, or ABR, less than 2 and a median joint and spontaneous ABR of 0.
In comparison, patients treated with the on-demand regimen had a median overall ABR of 41.5, a spontaneous median ABR of 21.6, and a median Annualized Joint Bleeding Rate of 38.1.
Additionally, in the same study, 40% of patients experienced zero bleeding episodes with ADYNOVATE prophylaxis. 57% of the patients in the study experienced zero joint and spontaneous bleeds.
When I consider patients looking to stay the course, I appreciate this clinical bleed prevention data.
Before we move on to the dosing schedule, let’s continue to review some important safety information for ADYNOVATE.
Warnings and Precautions
Hypersensitivity reactions, including anaphylaxis, have been reported with ADYNOVATE. Hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, pruritus, and nausea and vomiting. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.
In addition to providing bleed protection, ADYNOVATE also offers a simple, twice-weekly dosing schedule.
ADYNOVATE can be administered on the same 2 days each week.
For my patients looking to "stay the course," the simple, twice weekly dosing schedule, on the same two days each week, can be personalized to work with their lifestyle and needs.
So far, we’ve considered the clinical data of ADYNOVATE, but what might use look like in the real world?
Let’s take a look at a study that assessed ADYNOVATE prophylaxis in the real world.
A real-world study of prophylaxis with ADYNOVATE was conducted in 56 patients with hemophilia A who transitioned from prophylaxis with any recombinant factor product to ADYNOVATE prophylaxis.
This study included an assessment of real-life ABR and adherence among other endpoints.
Because this was a real-world study, it is important to note that there are some limitations. Patients were not randomized, observers were not blinded, and some subgroups were small in sample size. In addition, bleeding rates were patient-reported.
It’s also important to note that since these data are from a retrospective, observational chart review, they have less evidentiary value than data from prospective, controlled studies. Further confirmatory studies are required to draw any conclusions from these data.
In the retrospective, observational real-world study, the median ABR was 0.8 for the overall population, 0.8 for patients who received a prior SHL recombinant factor VIII product, and 2.4 for patients who received an EHL recombinant factor VIII product.
For patients 12 years and over, the median ABR was 0.8 and the mean ABR was 1.7.
During the study, 39% of patients experienced zero bleeding episodes.
This real-world experience with ADYNOVATE supports the proven bleed protection seen in the clinical study.
In addition, adherence to an ADYNOVATE regimen was reported in 56 patients.
In this study, 80% of patients reported good to complete adherence, which was defined as 80%-100% of prescribed doses taken. 13% of patients indicated moderate adherence, defined as 50%-79% of prescribed doses taken, and 5% of patients indicated poor adherence, defined as <50% of prescribed doses taken. One patient did not specify adherence.
Before we wrap up, let’s review some additional important safety information for ADYNOVATE.
Warnings and Precautions
Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.
A final important note with regards to ADYNOVATE safety information:
The most common adverse reactions (≥1% of subjects) reported in the clinical studies were headache, diarrhea, rash, nausea, dizziness, and urticaria.
To summarize, in this video we have considered a particular subset of patients: those comfortable with their current treatment regimen and looking to stay the course.
We have discussed some of the attributes of ADYNOVATE, including proven bleed protection, the simple, twice weekly dosing schedule, and important safety information, that may support the use of ADYNOVATE in this patient population.
Thank you for taking the time to consider ADYNOVATE for patients looking to "stay the course".
For more information on ADYNOVATE and the full prescribing information, please visit ADYNOVATEpro.com.