The words “recombinant therapy” and “von Willebrand disease (VWD)” have never occupied the same space. But now they can. In December 2015, the US Food and Drug Administration (FDA) approved Baxalta’s debut of Vonvendi®, the first recombinant von Willebrand factor (VWF) product for patients with VWD. The month before that, the FDA approved two other drugs that may be prescribed for those with bleeding disorders: Baxalta’s Adynovate® for hemophilia A and Gilead’s Genvoya® for patients with HIV-1.
Recombinant products for hemophilia A and hemophilia B were developed in the 1990s. The FDA approved the first recombinant FVIII product in 1992 and its counterpart for FIX in 1997. The advantage of recombinant products is that because they are not derived from human plasma, the risk of transferring viral diseases that are blood-borne is drastically reduced.
Prior to Vonvendi’s approval, patients with VWD had basically two treatment choices: a nasal spray or a plasma-derived factor product combining VWF and factor VIII (FVIII). Now they will have the option of treating with this VWF only product when necessary. Vonvendi is approved for on-demand treatment and control of bleeding episodes in adults 18 and older.
In the phase III clinical trial of Vonvendi, 81.8% of bleeds were resolved with one infusion. The therapy’s mean half-life was 21.9 hours. There were no serious adverse effects, but 2% of the subjects experienced itching. None of the participants developed an inhibitor. Baxalta expects Vonvendi to be available in the US later in 2016.
If the name Adynovate sounds familiar, that’s because it’s Baxalta’s recombinant factor product Advate® with a bonus—pegylation. Through pegylation technology, factor protein molecules remain in the circulation longer, providing extended protection from bleeds. Baxalta claims that Adynovate stays in the body 40%–50% longer than Advate. The goal of extended half-life products is to decrease the number of times patients infuse, while providing the same or better protection from bleeds. In its dosing information, Baxalta states that Adynovate is for twice-weekly treatment for patients with hemophilia A (factor VIII deficiency) who are 12 years and older.
The phase 3 clinical trial was conducted in 20 countries. The 137 patients 12–65 years old were placed in one of two arms: twice-weekly prophylaxis or on-demand, treating bleeds as they occurred. The prophylaxis group experienced 95% fewer bleeds; 38% of subjects had no bleeds. Further, 96% of bleeds resolved with one or two doses of Adynovate. Adverse effects occurred in 1% of the study participants, primarily headache and nausea.
Baxalta is conducting ongoing studies on patients with severe hemophilia A who are under 12 and were previously treated with other products, and also on adults undergoing surgery. A new study in 2016 will include treatment-naïve patients with severe hemophilia A.
To block HIV from replicating in the human body, drug manufacturers combine drugs that target it at different places during its life cycle. That’s the strategy behind Genvoya’s four-drug combination tablet. It contains the HIV inhibitors elvitegravir, emtricitabine and tenofovir alafenamide (TAF), and cobicistat, which boosts the drug levels in the bloodstream.
Genvoya has the same components as Stribild®, Gilead’s first quad therapy (approved by the FDA in 2012). However, it contains TAF, a different form of tenofovir than the tenofovir disoproxil fumarate (TDF) found in Stribild. TAF is less toxic to the kidneys and doesn’t decrease bone density to the degree TDF does. In addition, the dosage is reduced 1/10, so there is less TAF in the blood, but higher activity within the cells themselves.
Four clinical trials evaluated the safety and efficacy of Genvoya. “Results showed Genvoya was effective in reducing viral loads and comparable to the other treatment regimens,” the FDA said in a November 2015 press release.
The new HIV-1 drug is approved for patients 12 and up who’ve never been on antiretroviral therapy (ART), and for adults who have. Treatment-experienced patients must have their viral load suppressed to a level of < 50 copies of RNA/mL on a stable ART regimen for 6 months.
Still, Genvoya is not for all people. Patients with kidney damage are not good candidates for the drug. Further, the drug can cause bone density loss and redistribution of body fat, can interact with several other drugs and can trigger immune system responses.
Genvoya comes with a black box warning, the FDA’s highest alert. The label cautions that lactic acidosis, a dangerous buildup of lactic acid in the blood, and severe hepatomegaly with steatosis, enlarged liver with fatty liver, can occur and have caused deaths. Obesity and certain HIV therapies are believed to be factors, according to Gilead. The label also states Genvoya is not indicated for patients with hepatitis B virus infection.
Check with your doctor to see if you’re a candidate for any of these newly approved drugs.