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An experimental hemophilia drug developed by Alnylam Pharmaceuticals continues to staunch bleeding in patients followed for almost one year in an ongoing, mid-stage clinical trial, the company reported Monday.

The promising results could intensify an already heated competition to develop novel treatments for the inherited bleeding disorder. The Alnylam drug, developed in partnership with Sanofi, uses a technology called RNAi to shut down dysfunctional genes. It’s a promising approach that’s attracted billions in research dollars, but hasn’t yet been used in an actual drug approved for sale.


The company says the new data support its recent decision to advance its RNAi hemophilia drug —  known as fitusiran —  into phase 3 clinical trials. If it succeeds, the drug could potentially compete against an expected blockbuster hemophilia drug from Roche.

In the current study, 33 patients have been injected once a month with fitusiran. The results so far: 48 percent have not bled after a median observation period of 11 months, according to data reported Monday at the International Society of Thrombosis and Haemostasis Congress in Berlin. Some patients in the study have been followed for up to 20 months.

Before starting the study, patients were reporting a median of 20 bleeding events per year. That number was reduced to 1 following the fitusiran injections.


The patients have two types of the disease, hemophilia A and B. Fourteen of the patients have inhibitors —  immune system antibodies that interfere with clotting factors commonly used to treat hemophilia. Patients with inhibitors are the hardest to treat effectively.

For this group, the median annualized bleed rate fell from 38 to zero, although the median observation period was shorter at six months.

Sixty-four percent of the inhibitor patients have not bled since starting treatment with fitusiran.

“These are really encouraging numbers,” said Alnylam Chief Medical Officer Pushkal Garg, in a phone interview from Berlin on Sunday. “To show annual bleed rates of one and zero is remarkable, particularly for a treatment that is administered once per month with a subcutaneous, low-volume injection.”

One third of the fitusiran-treated patients in the study reported elevated liver enzymes, a possible signal of liver toxicity, though all these patients also had hepatitis C, Alnylam said. One patient with increased liver enzymes stopped participating in the study; the rest had no symptoms and their liver enzyme issues were resolved.

There were no blood clots reported by patients in the fitusiran study. That could help the drug stand apart from Roche’s hemophilia drug emicizumab, which had a handful of serious blood clots reported in its phase 3 studies.

“Net, net, in our view, though of small numbers and exploratory in nature, the data give us more confidence in the [fitusiran] program on the efficacy side,” said J.P. Morgan biotech analyst Anupam Rama. He added that “safety remains a key question.”

Roche intends to submit emicizumab for approval this year to treat hemophilia A patients with inhibitors to standard therapy. Sixty-three percent of patients receiving emicizumab reported zero treated bleeds compared with 6 percent of patients treated with bypassing agents, according to phase 3 study results previously announced. (Those results were also presented Monday at the Berlin meeting and published in the New England Journal of Medicine.)

Some analysts have projected emicizumab’s peak sales could hit $2 billion per year for patients with inhibitors, although that figure is hotly debated given the drug’s blood clotting safety issue. This leaves a potential opening for fitusiran, though its phase 3 trial won’t report data until 2019.

The Roche drug may eventually have other competition, too. Biomarin Pharmaceuticals, Spark Therapeutics, and Uniqure are all developing gene therapies to treat — and potentially cure — hemophilia.

Hemophilia drug franchises from Shire and Novo Nordisk are at risk of losing billions of dollars in sales if these new hemophilia drugs are approved. Though there are just 20,000 patients with hemophilia in the U.S., it’s a highly lucrative market.

On Sunday, Shire took the unusual step of fighting back with a preliminary injunction from a German court against Roche. Shire accused Roche of disseminating “inaccurate and misleading” information about the safety and serious adverse events that occurred in the phase 3 clinical trial of emicizumab, according to Reuters. In a statement, Roche said it stood behind the emicizumab data.

Alnylam, which is based in Cambridge, Mass., develops drugs that work through a process called RNA interference, or RNAi. All of its drugs, including fitusiran, are snippets of genetic code known as RNA that turn off genes producing disease-causing proteins. Fitusiran blocks the production of antithrombin, a protein made in the liver that prevents blood from clotting. Monthly injections of fitusiran reduce antithrombin in patients and increase corresponding levels of thrombin, another protein that promotes blood clotting.

Last October, Alnylam shares fell sharply after another of its RNAi drugs caused more deaths than a placebo in a phase 3 study. Work on that drug was halted.

But Alnylam shares have recovered this year, up 125 percent to date, on renewed investor optimism for its late-stage drug pipeline, including another RNAi drug, patisiran, targeting a rare nerve disease.

Alnylam shares fell 8 percent to $77.27 after the fitusarin data were presented, which J.P. Morgan’s Rama attributed largely to a “sell on the news” reaction given a recent run-up in the stock’s value.

Alnylam carries an almost $8 billion market valuation. It doesn’t yet have a drug on the market, which means investors are giving the company a lot of credit already for its late-stage RNAi pipeline, including fitusiran.

  • This is exciting news. I was a research nurse who worked on co-infected hemophilia patients in the early 90’s. No Pharma would help them and even the early HCV treatments were decided by pharma to be a waste of money. After THOUSANDS died from HIV infected blood while the physicians knew that blood was tainted w HIV this group should receive this medication FREE. And the insurance and biotech companies will likely get greedy and the patient suffers. Welcome to medicine in the USA.

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