The world’s first report from a clinical trial of genome editing inside the human body contains good news for
At a meeting of neurologists Saturday morning, researchers said that the first patients to get Intellia’s gene-editing treatment showed improvements in their inherited liver disorder that are as good, or better, than what’s achievable with the best drugs. There were no apparent safety problems.
Intellia stock (ticker: NTLA) has risen over 60% this year, to a Friday close of $88.83, as excitement built over the company’s pipeline of treatments that apply the gene-editing technology known as Crispr-Cas9, whose discovery won a Nobel Prize last year for
Intellia’s experimental treatment repairs an errant gene that causes transthyretin amyloidosis, or ATTR: a buildup of a misfolded protein in the nerves and heart that is often fatal. The interim data on the first six patients in the Phase 1 trial showed that a single dose of the treatment reduced blood levels of the harmful ATTR protein by an average of 87%, with one patient seeing a 96% drop after the first month. Higher doses were planned for some future trial participants, so the low-dose performance is probably better than what Intellia bulls expected.
“This is going to be exciting news for the doctors and exciting news for the patients,” Intellia chief executive
told Barron’s. “The efficacy and safety profile are extremely promising.”
The encouraging data is also good news for Intellia’s partner in developing the treatment,
(REGN), which will split profits if the treatment reaches market. But if their single-dose treatment proves out, it could be less welcome news for
(ALNY), two companies with fast-growing new drugs for treating ATTR amyloidosis.
Pfizer’s Vyndaqel and Vyndamax don’t stop patients’ livers from producing the misfolded ATTR proteins, but the drugs render the proteins less harmful. Infusions of Alnylam’s Onpattro or Vutrisiran are regarded as state-of-the-art because they can block production of most of the harmful proteins and reduce blood levels by 80% or more.
So an 80% reduction in ATTR proteins was the bogey for Intellia’s single-dose treatment, in the minds of analysts like RBC Capital Markets analyst Luca Issi. Saturday’s readout handily cleared that hurdle.
“The average [effect] is already beyond what you see with other treatment modalities,” said CEO Leonard. “We have one patient with over 96% reduction from baseline. That’s doesn’t happen with the other drugs.”
The treatment’s safety, so far, will allow the investigators to try higher doses of the Crispr therapy in the Phase 1 study. Leonard hopes that higher doses could achieve even better “knockdown” of ATTR protein levels. As blood clearance approaches 100%, the benefits increase logarithmically, he says, raising the possibility that the treatment won’t just halt the damage done by ATTR amyloidosis, but reverse it. There are an estimated 50,000 people worldwide born with ATTR, and between 200,000 and 500,000 who develop it later in life as a result of cumulative mutations.
Saturday morning’s data came out at the annual meeting of the Peripheral Nerve Society, in a presentation by the coordinator of the Phase 1 trial, Julian Gillmore, a professor at the U.K.’s Royal Free Hospital. A published report also appeared in The New England Journal of Medicine.
Intellia was one of three companies formed to exploit Crispr-Cas9 gene-editing, all within months of the Charpentier-Doudna discovery.
(EDIT) are also sponsoring clinical trials of treatments that aim to modify flawed genes by using the ability of Crispr-Cas9 molecules to home in on a specific sequence of DNA and snip it. Editas actually launched the first clinical trial of in-body Crispr editing, but is targeting a rare eye disorder in its first clinical trial and won’t report its data until later this year. Crispr Therapeutics has treated more patients in its clinical trials than both Intellia and Editas, but those therapies—for cancer and sickle-cell disease—are performed outside the body: A patient’s cells are harvested, edited in a lab, ex-vivo, and then reinfused.
The technologies used for Intellia’s in-vivo treatment for ATTR amyloidosis could be adapted for in-vivo editing of other genomic disorders, and the company has other clinical trials in preparation. Intellia also has worked on ex-vivo applications of Crispr, and on Tuesday, the company announced that it would contribute one of those projects to a new company bankrolled with $250 million from
While all these genetic medicine stocks are generously valued—despite little in the way of revenue and start-up losses—Intellia has trailed the market capitalizations enjoyed by the likes of Crispr Therapeutics or Alnylam.
That may be about to change.
Write to Bill Alpert at [email protected]