Experimental gene-silencing drug from Alnylam and Sanofi shows strong results in hemophilia

Alnylam CEO John Maraganore aims to compete with what is expected to be a blockbuster hemophilia drug from Roche.


n 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 fitusarin 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 Pushtal 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.

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.

At Friday’s $84.08 close, 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 fitusarin.


Apple supplier statistics suggest very strong holiday season sales

Apple’s market figures have always been that little bit harder to predict and accurately source. A lot of this has to do with Cupertino’s typical discreteness when it comes to revealing sales figures. It also doesn’t help that so many analysts and third parties take interest in the matter and publish their own reports.

However, a typically accurate way to approach things is to examine Apple’s vast supplier chain that is often a lot more willing to share information. In the latest such development, Dialog Semiconductor has reported notable positive earnings. RBC Capital Markets analyst Amit Daryanani dug into this a little further. According to him Dialog has raised its past quarter earnings expectations by 13% from $290 million to $320 million, now up to $345 million. Apparently Apple typically accounts to 75 to 80 percent of the company’s revenue and Cupertino tends to build iPhones 60 days out.

Putting two and two together, it becomes quite clear that Apple is preparing from strong sales in the last quarter of 2016. There are a few other observations to back this prediction up as well. First of all, Daryanani points out better than expected preliminary carrier data points. TheiPhone 7 and iPhone 7 Plus duo are proving quite popular.

Furthermore, a recent RBC survey among prospective buyers has noted a shifting tendency towards higher priced products. This includes 46% interest in the bigger 5.5-inch handset, up from 38% last year. Also, as far as storage options go, users seem to be more inclined to go for a 128GB model, rather than the now base 32GB one. Naturally, Apple makes more on those. Last, but not least, people seem to be warming up to other company products, like the Apple Watch with 17% interest, compared to 13% last year and Apple Pay – up from 16% to 24%. Plus, we can’t fail to account for the whole overheating/battery fiasco Samsung has been going through with the Galaxy Note7. It is sure to excerpt some influence on sales as well.

Taking everything into account, Daryanani now estimates a $125 target for Apple stock in Q4. As for revenue, he has raised his Q3 prediction to $47.3 billion from a total of 44.2 million iPhone unit sales. For the upcoming Q4, the numbers are $78.7 billion and 79 million handsets shipped.


users giving BlackBerry Priv a strong thumbs down, says AT&T exec

BlackBerry’s debut Android-powered cellphone Priv has were given a massive thumbs down from clients, at-least in step with AT&T. An unnamed, highdegree govt with the carrier bluntly told Cnet that thedevice “is truly struggling.”

The executive referred to that the handset frequently stuck the flamboyant of BlackBerry loyalistshandiest, and over-and-above that, majority of individuals who simply went beforehand and purchasedthe telephone discovered it hard to make a switch from the Canadian organisation‘s OS to Google’s OS.

we’ve seen greater returns than we would like,” the govt said.

according to the numbers discovered by way of BlackBerry, a complete of 600,000 Priv units have beensold in Q1 this year, properly below the 850,000 forecasted through analysts. Many believed that at $700the cellphone changed into overpriced, something which even CEO John Chen admitted in an interview.

shifting its consciousness a chunk, the organisation has already said that it now plans to launch twomid-range devices this 12 months – one with a Priv-like physical keyboard, at the same time as the alternative could be an all-touchscreen telephone.