May 22, 2023

The need-to-know this morning

Ironwood Pharmaceuticals announced an agreement to acquire VectivBio, developer of treatments for rare gastrointestinal diseases, for $1 billion. The deal values Vectiv at $17 per share, or an 43% premium over Friday's closing price. Ironwood markets Linzess, a treatment for irritable bowel syndrome and chronic constipation. The acquisition of VectivBio bolsters its GI-focused portfolio with the addition of apraglutide, an experimental medicine for short bowel syndrome, currently in a late-stage clinical trial.
Novartis purchased an experimental gene therapy for cystinosis, a rare, inherited disease, from AvroBio for $88 million.
Rain Oncology said its lead cancer drug failed to achieve the primary goal in a Phase 3 study for the treatment of dedifferentiated liposarcoma, a rare type of tumor that develops in fatty tissue.

heart disease

An antibody drug for ATTR-CM shows early promise

An experimental antibody drug has the potential to reverse disease progression in a heart condition called ATTR-CM, a small Phase 1 study published in NEJM shows. The medicine, developed by Neuroimmune and licensed by Alexion, the rare disease unit of AstraZeneca, seemed to reduce harmful protein buildup in the heart. The results were strong enough that the company plans on advancing the drug straight to Phase 3 study.

ATTR-CM, or transthyretin amyloid cardiomyopathy, is thought to affect some 400,000 people around the world. Patients' livers produce unstable proteins that misfold and clump into amyloid deposits in the heart, slowly impeding its function. The disease can either be caused by a genetic mutation or by aging, and without treatment, most patients die within five years of diagnosis. Two Pfizer pills are already approved for the disease, and another mRNA-targeting drug from Alnylam is being reviewed by regulators.

regulation

Advisers vote down Intercept's NASH drug

An FDA advisory panel voted against approving an experimental drug for the liver disease NASH made by Intercept Pharmaceuticals. Most committee members had serious concerns about fatal liver damage linked to the drug, as well as uncertainty over whether the drug was effective enough to improve patient lives. The panel also recommended rejecting Intercept's application for accelerated approval, waiting instead for more data on how the drug affects patient health in the long term.

"For this drug, we have clear evidence of safety risk — including very serious safety concerns with [liver injury] — but we have only evidence for potential efficacy," said James Floyd, an epidemiologist at the University of Washington. "It's impossible in my mind to ensure a good risk-benefit profile based on this surrogate endpoint data."

gene therapy

First-ever topical gene therapy wins approval

The FDA has approved a gene therapy made by Krystal Biotech to treat dystrophic epidermolysis bullosa, an inherited disease that causes extreme skin fragility. The topical treatment, called Vyjuvek, works by delivering a healthy copy of a collagen-producing gene that helps skin to heal. Unlike other approved gene therapies, Vyjuvek can be applied repeatedly if new wounds form or don't completely heal. Krystal Biotech said the treatment would cost $24,250 per vial — leading to an annual cost of $631,000, or $485,000 after government discounts.

A Phase 3 trial showed that 67% of wounds treated weekly with the gene therapy closed at six months, compared to 22% in patients given a placebo. The treated wounds also seemed to stay healed longer, and patients receiving the treatment reported improvements in their pain levels.

epigenetics

Proof-of-concept for CRISPRing the epigenome

Epigenome editing, a CRISPR technique that changes the chemical coding that controls the activity of genes but doesn't change the underlying DNA itself, has demonstrated some efficacy in monkey models. When the tool was used to dampen the PCSK9 gene that's associated with high cholesterol, LDL levels dropped more than 50%, a scientist at Tune Therapeutics said during the American Society of Gene and Cell Therapy conference last week. This preclinical work suggests that efforts to alter epigenetic could actually work.

"This Tune data looks beautiful," one longtime gene-editing researcher who was not involved in the study told STAT. "It does really look like they were able to silence that gene in a very long-term way and they were able to see clinical benefits from that."

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