Gilbert Dryden probably only has enough medication to get him through the end of October, his mother, Madison, figures.<\/p>\n\n\n\n
Seven-month-old Gilbert has a rare genetic condition called Barth syndrome, one that can have dire consequences, like heart failure, extreme muscle weakness and a dramatically reduced life expectancy.<\/p>\n\n\n\n
Children who die early often don\u2019t see their fifth birthday. Two infant deaths were reported within the past week, according to the Barth Syndrome Foundation.<\/p>\n\n\n\n
What\u2019s been keeping Gilbert alive and functioning relatively well, according to his family, is an experimental drug called elamipretide, made by Stealth BioTherapeutics. Small studies have suggested<\/a> it\u2019s safe and effective in treating the ultra-rare illness. Just 150 people in the U.S. have the condition.<\/p>\n\n\n\n \u201cOur kids are dying. We have seen that this drug works,\u201d said Kate McCurdy, a co-founder of the Barth Syndrome Foundation. \u201cThis drug totally saves the lives of babies.\u201d<\/p>\n\n\n\n After a more than decade-long process to bring the drug to market, the treatment\u2019s approval has repeatedly hit roadblocks with the Food and Drug Administration.<\/p>\n\n\n\n One setback occurred in the spring, when an FDA inspection found problems at a Stealth manufacturing facility. The problems weren\u2019t made public, but apparently weren\u2019t egregious enough to warrant regulatory action. The company said the issues have been resolved.<\/p>\n\n\n\n In late May, after an advisory panel voted earlier (in October 2024) to recommend the therapy, the FDA declined to approve it. The agency didn\u2019t reveal why.<\/p>\n\n\n\n An ultra-rare disease like Barth syndrome with an ultra-small population of patients who can be tested for clinical efficacy faces barriers for FDA drug approval. There aren\u2019t enough patients to do robust, randomized clinical trials, McCurdy said.<\/p>\n\n\n\n \u201cIt is virtually impossible to conduct trials that yield data that are conclusive beyond a reasonable doubt. Statistically, you just can\u2019t do that,\u201d she said.<\/p>\n\n\n\n Weeks later and following a meeting between Needham, Massachusetts-based Stealth and the FDA in late June, the real bombshell came: The company said the agency informed Stealth on Aug. 4 that it would need to resubmit a new drug application \u2014 for the third time.<\/p>\n\n\n\n It could use a special pathway called \u201caccelerated approval\u201d in that submission, but the manufacturing issue would extend the timeline to review elamipretide for at least another six months, according to the company.<\/p>\n\n\n\n Stealth said that no additional clinical data or safety data was requested. But without any course correction in the process, the private company could run out of money.<\/p>\n\n\n\n The delay is devastating to families like the Drydens.<\/p>\n\n\n\n \u201cWhen we heard this news, we immediately went to the fridge to count how many vials we have left, because that\u2019s how long we have this medication. That\u2019s the only guarantee we have right now that Gilbert is not going to die,\u201d said Madison Dryden, 35, of Aurora, Colorado. \u201cIt\u2019s the highest level of desperation.\u201d<\/p>\n\n\n\n On Monday, Stealth announced that it did submit its third application for approval of elamipretide \u2014 asking for an accelerated pathway under a significantly tighter timeline than what the agency initially recommended.<\/p>\n\n\n\n What is Barth syndrome?<\/strong><\/strong><\/p>\n\n\n\n Madison Dryden and her husband, Andrew, weren\u2019t sure what was wrong with Gilbert in the hours and days after his Christmas Eve birth in 2024.<\/p>\n\n\n\n \u201cHis heart function was so low. He was so sick, his body and his feet were purple, his hands were purple,\u201d Dryden said. \u201cHe couldn\u2019t eat.\u201d<\/p>\n\n\n\n Gilbert was admitted to the neonatal intensive care unit and received lifesaving care as doctors urgently tried to figure out a diagnosis.<\/p>\n\n\n\n Within a matter of days, Dryden said, Gilbert was airlifted to Children\u2019s Hospital Colorado with a heart that was struggling to adequately pump blood. The underlying cause was soon revealed: Barth syndrome.<\/p>\n\n\n\n The disease impairs cells\u2019 mitochondria, which are kind of like tiny batteries that generate energy for cells to function correctly.<\/p>\n\n\n\n The chromosomal disorder almost exclusively affects boys. Roughly 85% of early deaths occur before age 5. Those who survive longer are usually given heart medications and may need a heart transplant.<\/p>\n\n\n\n Kids with Barth syndrome often rely on drugs like beta blockers and ACE inhibitors to keep their hearts functioning as well as possible.<\/p>\n\n\n\n Gilbert was fortunate, at least initially. He found a lifeline through access to the treatment from Stealth. Elamipretide, a daily injection, works by helping to repair the damaged mitochondria.<\/p>\n\n\n\n In clinical trials, patients showed a 45% improvement in muscle strength and a 40% improvement in heart function, according to the drugmaker. Most participants have safely remained on the drug for over eight years.<\/p>\n\n\n\n In October 2024, an advisory committee to the FDA voted 10-6 in support<\/a> of the therapy, paving the way for the agency to clear the first drug to treat Barth syndrome. The FDA isn\u2019t required to follow the advisory committee\u2019s guidance, but it almost always does<\/a>.<\/p>\n\n\n\n A spokesman for the Department of Health and Human Services, which oversees the FDA, wrote in an email that the \u201cFDA did carefully consider the advice of the advisory committee members, including their rationale for their vote. While there is often a high rate of agreement between FDA and advisory committee recommendations,\u201d the spokesman said, \u201cthere is not always concordance.\u201d<\/p>\n\n\n\n \u2018Compelling medical need\u2019 for approval<\/strong><\/strong><\/p>\n\n\n\n After the advisory committee\u2019s recommendation, the FDA\u2019s rejection was unexpected.<\/p>\n\n\n\n \u201cIt is a small sample size,\u201d said a former FDA official who was involved in the drug approval process. The person asked not to be identified in order to speak freely.<\/p>\n\n\n\n But the former official was quick to point out that given the advisory committee recommendation for approval, the \u201cincredibly compelling medical need\u201d of those living with Barth syndrome and the small sample of individuals who seemed to have benefited from the treatment, it certainly appeared that elamipretide was going to make it across the finish line.<\/p>\n\n\n\n A lack of continuity in leadership, however, may have added to the already difficult challenge of guiding the treatment through the final hurdles, the former official said.<\/p>\n\n\n\n The FDA has seen many top officials leave the agency<\/a> in recent months.<\/p>\n\n\n\n \u201cThose who have taken over are not as familiar, or perhaps it\u2019d be more appropriate to say they\u2019re inexperienced with how one does drug approvals, how one drives things forward, and they\u2019re also somewhat fearful of the current environment,\u201d the former official said. \u201cAnd I think that\u2019s led to an adverse outcome for some of these rare disease products.\u201d<\/p>\n\n\n\n The HHS spokesperson didn\u2019t immediately respond to a request Monday for comment about the agency\u2019s rejection of the drug or leadership issues.<\/p>\n\n\n\n