Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Phenylketonuria.
Treatment: Palynzig.
The insurer denied Palynzig.
The denial is overturned.

The patient is a woman. She has classical PKU (phenylketonuria). She is on a phenylalanine and natural protein restricted diet. She takes phenylade 60, but she still has blood phenylalanine levels that are on average above 10 mg (milligrams) percent/600 micromolar. She does not respond to Kuvan. Her provider has requested Palynziq injectable therapy for control of her PKU (phenylketonuria).

Yes, the treatment with Palynzig is medically necessary.
This classical PKU (phenylketonuria) patient is on a protein restricted diet and is receiving a specialized low phenylalanine PKU (phenylketonuria) formula but still has blood phenylalanine levels above 10 mg percent/600 micromolar. Her geneticist has qualified in the Palynziq REMS (risk evaluation and mitigation strategy) program, and therefore has the competencies to prescribe Palynziq for treatment of PKU (phenylketonuria) and to monitor her during the 9 to 12 week treatment initiation phase of this therapy.

Treatment of this woman's classical PKU (phenylketonuria) with Palynziq is medically necessary and clinically appropriate. This treatment is consistent with the currently recognized standard of practice in treatment of Classical PKU (phenylketonuria) and is highly effective in controlling blood phenylalanine levels in individuals with this metabolic disease. No other available drug or medication is capable of providing the PKU (phenylketonuria) control that is available with this injectable drug. Use of this FDA (United States Food and Drug Administration)-approved drug in this patient meets the current standard of care in medical genetics, biochemical genetics, and is approved by the FDA (United States Food and Drug Administration) for this indication, namely treatment of classical PKU (phenylketonuria).

According to Levy et al (2018), "Phenylketonuria (PKU) is a genetic inborn error in metabolism that impacts many people globally, with profound individual and societal consequences when left untreated. The journey of phenylalanine ammonia lyase (PAL) from plant enzyme to enzyme substitution therapy for PKU [phenylketonuria]) is a fascinating story that illustrates the importance of collaboration between basic scientists and industry in the drug development process. The story begins with the curiosity of plant physiologists about the origin of lignin, a polymer involved in maintaining the rigidity of plants. They learned that the critical element in this synthesis was an intermediary enzyme that deaminates phenylalanine to cinnamic acid and ammonia (later called phenylalanine ammonia lyase or PAL). Recognition of this ability to metabolize phenylalanine led to subsequent consideration of PAL [phenylalanine ammonia lyase] as a treatment for PKU [phenylketonuria]. This was initially attempted as enteral therapy with extracted enzyme, but that showed only minimal efficacy. Crucially, further development of PAL [phenylalanine ammonia lyase] as a therapy for PKU [phenylketonuria] required quantities of enzyme that could only be obtained after successfully cloning the gene, expressing the enzyme in vitro and modifying the protein via PEGylation [attachment of polyethylene glycol] to enable parenteral administration of this non-mammalian enzyme. Ultimately, PEGylated [attached polyethylene glycol] PAL [phenylalanine ammonia lyase] was developed as an enzyme substitution therapy for PKU [phenylketonuria] now approved under the name 'Palynziq.' The multidisciplinary academic-industrial partnership engaged throughout this process has been key to the successful pursuit of this therapeutic possibility and serves as a model for the development of future innovative therapies.'

In addition, the FDA (United States Food and Drug Administration) package insert states, "Palynziq is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L [liter] on existing management." Use of this injectable drug to treat this woman's PKU (phenylketonuria), whose initial blood phenylalanine levels before treatment were 1500, well above six hundred, meets the above FDA (United States Food and Drug Administration)-approved criteria.