By Holly Giles | Deputy Editor
Hutchinson-Gilford progeria syndrome, shortened to progeria, is a condition of rapid ageing which affects 1 in every 4 million babies born worldwide. It is a rare genetic condition that causes the child’s body to age rapidly, meaning most patients do not live beyond 15.
The condition is caused by a mutation in a single gene which interferes with the protein behind making laminin A. This holds the nuclei of cells in place. The mutation means the protein has an extra piece attached (called progeria) which gets stuck in cell membranes, causing the cells to prematurely age. This leads to bone loss, hardening of the arteries, stiffening of connective tissues and eventually fatal heart attacks and strokes as a result of these changes. People naturally produce more progeria as they age but children with the condition produce far too much of it.
There is currently no cure for progeria but treatments include supportive care and therapies towards the complications associated with the condition. However, this could soon change as the FDA approved the first drug for progeria treatment in November 2020, called Zokinvy.
In a clinical trial with 62 children the drug was shown to increase life span by 3 months during the first 3 years of treatment. These children were then followed and on average showed that their lifespan was lengthened by 2.5 years over the 11 years of treatment. Zokinvy works to block some of the progeria being produced so less of it accumulates in affected children. This reduces the pace of premature ageing. The drug is unable to fully block production but does reduce levels.
The Direction of the Office of Rare Disease, Pediatrics, Urologic and reproductive Medication, Hylton V. Joffe, explained the significance of the approval from the FDA:
“Hutchinson-Gilford progeria syndrome and progeroid laminopathies are rare genetic diseases that cause premature aging and death and have a debilitating effect on people’s lives… With [the] approval, Zokinvy is the first FDA-approved medication for these devastating diseases. The FDA will continue to work with stakeholders to advance the development of additional new, effective and safe therapies for these patients”
This sentiment was added to by David Cory, President and Chief Executive of Eiger, who explained:
“The FDA approval of Zokinvy is the result of a pioneering partnership between Eiger BioPharmaceuticals and PRF to bring the first approved therapy to children, young adults and families living with this devastating disease. We are very proud that the first drug approval at Eiger confers a survival benefit to patients with one of the most ultra-rare and, ultimately fatal, pediatric diseases”.
Alongside the approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher to Eiger (the developers) to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases. The company has recently said they plan to sell the voucher, which is estimated at $100 million, and to share the proceeds with the Progeria Research Foundation, who helped in the development of the drug.
Monica Kelinman, a pediatric critical care doctor at Boston Children’s Hospital involved in the clinical trials, reminded readers that whilst this is promising it is not a final result. She said: “This is not a cure. We’ve hopefully extended the lifespan that [the children] have by slowing the pace of the disease” but, she explained, this does not extend it to normal.
Now that it has been approved, the focus has moved to testing other drugs in combination with Zokinvy as a means to improve the efficacy of the treatment and reduce the side effects to allow higher doses to be used. Currently, the amount that patients can receive is limited by the drug’s side effects, which include vomiting, diarrhea and fatigue. This future research could lengthen the lives of children with progeria further and help them to eventually live a normal life.
Overall, the approval of Zokinvy marks a key landmark in progeria care as clinicians will now have a treatment which can give children an extra 2.5 years of life; this will make a huge difference to patients and their families. It also offers hope that in the future this figure will increase so patients can one day expect a normal lifespan.