FDA Lifts Holds on Trials

The FDA has lifted holds on two sets of clinical trials, one for an experimental treatment of several cancers and the other a gene therapy targeting Duchenne’s muscular dystrophy.

Epizyme announced last week that the agency is allowing six U.S. trials for its drug tazemetostat to resume after stopping them in April because a child in one of them developed secondary T-cell lymphoma. The child stopped taking tazemetostat and underwent treatment for the new cancer.

The FDA OK’d restarting the trial after Epizyme turned over all efficacy and safety trial data and convened a panel of experts to validate the drug’s safety.

Tazemetostat – which was granted orphan status in June 2017 – is being tested to treat several cancers, including non-Hodgins lymphoma.

Sarepta Therapeutics last week announced the FDA had also greenlighted its request to continue a clinical trial on an early-stage gene therapy program for Duchenne’s, which it paused in July after finding trace amounts of DNA in the treatment. The company said it never gave the compromised therapy to any patients in the Columbus, Ohio-based trial but switched suppliers just in case.

Duchenne’s is a rare disorder that mostly afflicts boys. The rapid decline in muscle strength and mass usually means victims don’t survive to adulthood.

The hope is that Sarepta’s gene therapy will boost the amount of microdystrophin to stem muscle loss. Microdystrophin is a smaller version of the protein dystrophin missing in Duchenne’s sufferers.

The company says it hopes to re-open clinical trials by the end of the year.

FDA: $18M for Rare Disease Trials

The FDA is doling out more than $18 million in grants to support clinical trials for rare diseases, the agency has announced.

The grants will roll out over the next four years and be given to 12 principal investigators, a mix of major academic institutions and private companies. The money comes from the FDA’s Orphan Products Clinical Trials Grants Program.

Here’s the list of grant recipients:

• Leonide Saad of Alkeus Pharmaceuticals in Cambridge, Mass., $1.75 million over four years for a Phase II study of experimental drug ALK-001 to treat Stargardt disease, which causes macular degeneration in children and adolescents;
• Keith Lindor of Arizona State University-Tempe, $2 million over four years for a Phase II trial of oral vancomycin for the treatment of primary sclerosing cholangitis, a potentially fatal liver disease;
• Shlomo Melmed of Cedars-Sinai Medical Center in Los Angeles, $2 million over four years for a Phase II trial of selicilib to treat Cushing disease, a non-cancerous tumor that affects the pituitary gland;
• Yvonne Saenger of New York City’s Columbia University, $750,000 over the next three years for a Phase I trial of talimogene laherparepvec to treat advanced pancreatic cancer;
• Eric Sorcher of Emory University in Atlanta, $1.5 million over three years for a Phase I/II study of Ad/PNP fludarabine to treat head and neck squamous cell carcinoma;
• John Maslowski of Fibrocell Technologies in Exton, Pa., $1.5 million over four years for a Phase I/II study of gene-modified fibroblasts to treat dystrophic epidermolysis bullosa, a genetic disorder that leaves the skin fragile and easily blistered;
• Amy Dezern of Johns Hopkins University, $750,000 over three years for a Phase I/II study of T cell treatments of myelodysplastic syndrome, a group of blood disorders;
• Yang Liu, of Oncolmmune in Rockville, Md., $2 million over four years for an experimental drug called CD24Fc to prevent graft versus host disease, a potentially fatal side effect of stem cell transplants;
• Zachary Rome of Patagonia Pharmaceuticals in Woodcliff Lake, N.J., $1.5 million over three year for a Phase II study of isotretinoin for treatment of congenital ichthyosis, a skin disorder that affects newborns;
• Stephanie Seminara of the General Hospital Corp. in Boston, $1.4 million over four years for a Phase II study of kisspeptin for dopamine agonist intolerant hyperprolactinemia, a disorder that causes the body to over-produce the hormone prolactin, which stimulates breast milk production;
• Kyriakie Sarafoglou of the University of Minnesota, $1.4 million over three years to study a hydrocortisone pump to treat congenital adrenal hyperplasia, an adrenal gland disorder; and
• Matthew Laughon of the University of North Carolina, $2 million over four years for a Phase II study of sildenfill to prevent bronchopulmonary dysplasia, which afflicts the lungs of newborns.

Heart Clamp Scores Big in Trials

A small clip attached to a heart valve significantly helped heart failure patients in clinical trials, researchers report.

Abbott’s MitralClip, fastened to the “leaflets” of the heart’s mitral valve, is designed to help prevent mitral regurgitation, which occurs when the mitral valve doesn’t completely close allowing blood to flow backward into the heart, forcing it to work harder to pump blood.

Mitral regurgitation is the most common heart valve disease, affecting nearly one in 10 older Americans that — left untreated — kills nearly 57 percent of its sufferers within a year.

Researchers enrolled 614 heart failure patients at 78 trial sites in the U.S. and Canada to see if the MitralClip could help improve or slow symptoms. All took their regular heart meds and 302 also received MitralClips.

The findings, published in the New England Journal of Medicine: There were 47 percent fewer hospitalizations and 38 percent fewer deaths among the MitralClip patients during the two-year study.

Patients who received the clip also reported “significant” improvements in their quality of life and daily activity, the research team reported.

People who suffer from severe heart failure are often too sick to undergo open heart surgery and have their mitral valves replaced.

The clamp, which first obtained FDA premarket approval in 2013, is threaded through a blood vessel in the groin.

Lead researcher Gregg W. Stone, a cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said the surgery offers heart failure patients “substantially more hope.”

UK Allows E-Consent in Trials

Regulators in the UK and Northern Ireland will allow researchers to collect electronic signatures for informed consent in clinical trials, officials announced last week.

Health agencies in England, Scotland and North Ireland say most trials can get by with “simple” electronic signatures — a stylus or finger-drawn signature, a tick box and consent declaration, a unique representation of characters or a finger-print scan.

Higher risk trials, including Phase I healthy volunteer studies, can also use simple signatures but it’s recommended they stick with finger- or stylus-drawn signatures so they can be compared with previous patient signatures in audits.

Remote clinical trials, however, may need to use “advanced” or “qualified” e-signatures, regulators said.

Advanced signatures are more akin to passwords. They’re uniquely linked to the signer, can identify him or her and are tied to data within the signature that can detect any variations or changes. Qualified signatures are uniquely linked to the signer and are created by a special, certified electronic device.

Read the E-signature statement here: www.fdanews.com/09-25-18-UKEconsent.pdf.

Getting Closer to a TB Vaccine

An experimental tuberculosis vaccine protected participants in a large clinical trial 54 percent better than those who took a placebo, GlaxoSmithKline reported last week.

The drugmaker recruited nearly 3,600 patients in Kenya, South Africa and Zambia who tested positive for latent TB but weren’t yet symptomatic.

About half were given the experimental vaccine M72/AS01 and the rest received a placebo during trials held between August, 2014 and November 2015.

Nearly three years later, 10 people in the vaccine group and 22 who received the placebo developed full-blown TB, researchers reported.

The World Health Organization estimates close to a quarter of the world’s population is infected with tuberculosis. Only a handful of people who carry the germs — between 5 percent and 15 percent — will develop TB but it remains the world’s leading cause of infectious death and there are more than 10.4 million new cases each year.

ACRP: Sites Rate Sponsors, CROs

Clinical site employees say they have better relationships with drug sponsors than with CROs, a new survey finds.

The Association of Clinical Research Professionals and the Avoca Group surveyed 281 site staffers online between January and March 2018 to gauge their satisfaction with sponsor/CRO colleagues and protocol designs – and how likely they were to recommend a sponsor or CRO to others.

Sponsors scored higher overall on questions relating to their protocol knowledge, responsiveness to questions or concerns, communication style, clarity of instructions and the ability to manage time efficiently.

Staffers ranked “communication style” as the most important factor in their attitude toward clinical relationships.

Sites also seemed to have more confidence in sponsors’ ability to execute trials, rating them above CROs on questions such as reliability of clinical supplies, initiation or training, support for patient recruitment and retention and setting realistic goals.

Link to the survey here: https://www.acrpnet.org/resources/white-paper-site-perspectives-on-becoming-a-sponsor-or-cro-of-choice.