George Lee

The @FDA has put rare disease patients at the center of its public agenda this week. Senior leadership appeared at National Organization for Rare Disorders summit & yesterday the agency held a major public meeting on rare diseases. I welcome that commitment. With the November 22 decision date for deramiocel approaching, I want to see it reach the families living with Duchenne muscular dystrophy. I believe FDA should approve deramiocel for an appropriately defined indication focused on preserving upper limb function, with honest labeling, appropriate safety precautions, & continued study. I want to explain why this matters so much to me. To be transparent, I worked full time at @Capricor Therapeutics $CAPR FOR 2 years (2015-2017 - that's how long this process takes) & helped initiate its muscular dystrophy program. I began cell therapy research as a teenager & have spent decades working on cell biology, regenerative medicine, & therapeutic development for pediatric rare diseases. Over the years I have stayed in touch with patients (some nearly every day), parents, and advocates connected to this program. I have heard their hopes, their frustrations, and their concerns about what another delay could mean. Those conversations stay with you. For a boy or young man with Duchenne who has already lost the ability to walk, preserving arm and hand function can mean continuing to feed himself, lift a drink, drive a power wheelchair, or bring a hand to his face. These abilities shape how much of his day he can manage independently and how often he must ask someone else for help. A change that looks modest on a clinical scale can matter enormously when it affects something a person does every day. Patients and families have essential expertise in explaining its value. FDA heard those priorities at the advisory committee meeting. Their testimony should help shape how the agency evaluates clinical meaning, acceptable risk, and the consequences of waiting. There is a scientific basis for taking deramiocel seriously. The program includes two randomized, blinded, placebo-controlled trials. The published HOPE-2 and HOPE-3 studies reported benefits in upper limb function. In the newer extension findings, patients initially assigned to placebo showed slower decline after switching to deramiocel. Noting that the extension was open label and lacked a concurrent placebo group, I nevertheless find the pattern across these studies compelling enough to support a serious case for approval. FDA’s July review raised some scientific questions, and the additional data and analyses in the amended application should be evaluated directly against those concerns. The amended application now focuses on upper limb function. That claim deserves a careful assessment of the evidence supporting it. Uncertainty about cardiac benefit remains, and the label should accurately reflect what has been established. This is where senior FDA leadership can make its commitment to rare disease patients consequential. Ensure that the full amended evidence receives a rigorous review informed by Duchenne specialists, treating physicians, and the people living with this disease. Resolve the remaining issues as directly and promptly as possible. Evaluate the treatment against a clearly defined indication and the applicable approval standard. The agency’s new rare disease initiative recognizes that evidence must be evaluated in the context of the disease, the patient population, and what can realistically be studied. I agree. That principle should inform applications already under review as well as future development programs. Families waiting today should have the benefit of that thinking. As a physician, I also want the consequences of delay included in the assessment. Another study may answer an important question. It also takes time (many many years) from patients living with progressive disease. A decision to wait carries consequences for the person who needs help eating next year when he could feed himself this year. That possibility deserves serious consideration alongside potential uncertainties of treatment. Approval would allow eligible patients, their families, and their physicians to discuss whether deramiocel makes sense for them. They could weigh the potential benefit, the infusion burden, the known risks, and whatever uncertainty might remain. An accurate label and a careful medical discussion would help them make that choice. FDA has an essential responsibility to establish that a treatment meets the standard for approval. Patients and physicians then have their own responsibilities in deciding whether to use it. I want a regulatory system that performs its role rigorously and gives those decisions room to happen when the evidence supports them. Putting American patients first requires that entire process to work. To Acting Commissioner @FDA_KyleD, CBER Director Karim Mikhail, and the deramiocel review team: please use the remaining review period to pursue a scientifically defensible approval for the indication the evidence supports. I believe the published findings and additional follow-up warrant that effort. I believe preserving upper limb function deserves substantial weight. And I believe the families who have participated in these studies and spoken so openly about their lives deserve a decision that fully accounts for what they stand to gain and what continued waiting may cost them. I want the boys and young men whose families I have heard from over these years to have the opportunity to discuss this treatment with their physicians while they still have function to preserve. FDA’s renewed commitment to rare disease patients gives me hope that this can happen. I am asking its leadership to do everything the science and the law allow to make it possible. Image: From @CDCgov DMD Resources page