Bringing FDA-approved NGS tests to the masses

Published in Drug Discovery News

SAN DIEGO—Expanding applications of its recently FDA-approved MiSeqDx in-vitrodiagnostic next-generation sequencing (NGS) system, Illumina has agreed to help develop a multigene, NGS-based test to identify prospective patients for Vectibix (panitumumab), an anti-EGFR monoclonal antibody drug developed by Amgen, a drug company based in Thousand Oaks, Calif.

 

“This collaboration is consistent with our strategy to bring the power of NGS to clinical diagnostics,” said Nick Naclerio, senior vice president of corporate and venture development and general manager of Illumina's Enterprise Informatics business. “With three FDA-cleared NGS products in our portfolio, we intend to complement internal development programs by taking products developed with external partners through the FDA submission process. Amgen is a key partner given their leadership in therapeutic development and strong track record in commercializing novel products.”

 

“NGS provides an advantage over traditional technologies that typically detect only one or a few variants,” added Dr. Rick Klausner, chief medical officer and acting general manager of Illumina’s oncology business. “Multigene NGS panels provide a more complete genetic picture of each patient's tumor, which can better inform critical treatment decisions. We see the development of multigene diagnostic tests as a natural evolution to improve cancer care and outcomes.”

 

Vectibix has regulatory clearance in the United States and the European Union for targeting metastatic colorectal cancer that has not responded to chemotherapy.

 

At present, Illumina has just three tests available for the MiSeqDx instrument, which uses the sequencing-by-synthesis method of assaying. There is a universal kit allowing researchers to make their own tests, and two tests for assaying genes connected with cystic fibrosis. MiSeqDx’s November 2013 FDA approval makes it the first NGS platform with that imprimatur. To build on that achievement, market analysts report that the company has eagerly sought partnerships like the new one with Amgen.

 

Using the Illumina platform, the test to be developed could solve a key problem Amgen has with Vectibix: the drug is aimed at less-aggressive forms of the cancer and is restricted for patients who have, or do not know whether they have, KRAS mutations, which are associated with more aggressive cancers and lower survivability. But there is not yet an FDA-approved test to determine KRAS mutation status for potential Vectibix patients.

 

According to a report on GenomeWeb.com, Amgen is also working with Dutch-headquartered QIAGEN to develop a polymerase chain reaction kit to detect KRAS mutations that might affect Vectibix’s usefulness. The financial details of that deal are not being made public.

 

The Illumina test would not only use NGS technology, but would also detect RAS oncogene mutations beyond just those in KRAS.

 

“We believe the NGS platform offers great market potential,” reads a report from Zacks Investment Research, which also says the analysis firm is “optimistic about management’s expansion strategy,” which involves working with diagnostic and therapeutic developers and providers. In January alone, the company announced agreements with both Quest Diagnostics and LabCorp, with Illumina providing equipment and supplies for its partners to develop new lab tests.

 

Under the terms of the Vectibix deal, Illumina will develop the test, which will be validated by Amgen. Then both companies will work to get FDA and European approval, before Illumina commercializes the test.

Absorbing more ‘bad’ cholesterol

Published in Drug Discovery News

THOUSAND OAKS, Calif.—Completing a key step toward filing for regulatory approval of a broadly applicable cholesterol-reducing drug, Amgen has announced promising results from its fifth Phase 3 trial—the RUTHERFORD-2 trial—of evolocumab, a fully human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood.

 

LDL-C is a major risk factor for cardiovascular disease, and more than 71 million Americans have high LDL-C, according to the U.S. Centers for Disease Control and Prevention. Patients who have both high cholesterol and high cardiovascular risk are key target markets for evolocumab.

 

While the trial’s full results will be announced in Washington, D.C., at the American College of Cardiology’s 63rd Annual Scientific Session in late March, Amgen has said that the drug successfully combined with statins and other lipid-lowering drugs to reduce LDL-C, also called “bad” cholesterol, for patients with heterozygous familial hypercholesterolemia.

 

Previous trials have found evolocumab useful for patients with high cholesterol who were not previously getting anti-lipid treatment, as well as those already on statin drugs, and those who cannot tolerate statins, the most common type of anti-cholesterol drug.

 

While statins inhibit an enzyme that controls production of cholesterol in the liver, evolocumab binds to PCSK9, blocking it from binding to LDL receptors on the surface of the liver, according to the company’s description of the drug. That frees up more LDL receptors to remove LDL-C from the blood.

 

According to the company, a total of 13 trials are slated, including testing varying methods of injecting the drug and different frequencies of administration. About 30,000 patients will be involved, including those with cardiovascular disease, hyperlipidemia, coronary atherosclerosis and familial hypercholesterolemia (whether heterozygous or homozygous).

 

Those latter conditions, which are genetic, cause high levels of LDL-C starting at birth, and place patients at high risk for cardiovascular problems early in life. Heterozygous familial hypercholesterolemia affects about one in every 300 to 500 people worldwide, according toWorld Health Organization data.

 

The results so far will be shared with regulators, in hopes of securing approvals in 2014, the company said in a statement to DDNews. The exact timeline depends on results of ongoing trials.

 

Since Jan. 23, Amgen has touted positive top-line results for evolocumab from the Phase 3 GAUSS-2 trial in statin-intolerant patients with high cholesterol, the Phase 3 LAPLACE-2 trial in combination with statins in patients with high cholesterol and the Phase 3 RUTHERFORD-2 trial in patients with heterozygous familial hypercholesterolemia.

 

Of the most recently announced top-line results, Dr. Sean E. Harper, executive vice president of research and development at Amgen, said, “Data from the RUTHERFORD-2 study suggest that evolocumab, when used as an add-on therapy to existing lipid-lowering medications, may offer a new treatment option for patients with heterozygous familial hypercholesterolemia. The RUTHERFORD-2 study is the fifth pivotal LDL-C lowering study in our Phase 3 program. The robust data from these five studies will form the basis of our global filing plan, and we look forward to discussions with regulatory agencies.”

Press Releases: Beyond politics

Published in the Portland Phoenix

Today’s US media environment might well seem extremely gay-friendly. American mainstream media consumers saw a fair amount of coverage of anti-gay discrimination in Russia in the lead-up to, and during, the Winter Olympics in that country (read more on this topic on page 10); there was relatively little outcry when President Barack Obama selected several gay former Olympians to represent the United States in the audience. Johnny Weir both dressed and behaved flamboyantly on NBC’s nightly figure-skating broadcasts. Heck, even marriage equality gets little more than ho-hum headlines these days as this vital civil-rights issue continues its progress around the country.

But there is still much more to be done, and last weekend, a one-day conference at Colby College in Waterville sought to explore what, and how.

Called “Queering the Media,” the event, put together by members of Colby’s all-inclusive LBGTQ-plus-allies support group The Bridge, appeared to be less about news-media coverage and more about modern culture, as described by organizers Andy Kang and Sonja Hagemeier.

The intent was that “‘queering’ would be a relatively broad and very widely interpreted term,” Kang says. Looking at “how the media portrays or represents, or tries to represent, or fails to represent, people who don’t fit into mainstream culture” is important, he says, because it can help remind consumers of that information that other viewpoints and experiences exist.

This is important in Maine particularly, says Hagemeier, because “a lot of people think of Maine as really isolating, especially for queer people.” She spoke in almost mystical tones about Portland, a place she has heard is “very very queer friendly,” while observing that it is only slowly that “people are getting used to the idea” in other parts of Maine.

Their conversations at the conference, including presentations by students and current and former Colby faculty, as well as noted queer scholar Jack Halberstam, covered athletic environments, video games, and churches’ roles in social-justice efforts. That’s certainly a departure from most coverage of LGBTQ issues in Maine’s mainstream media. In those outlets, Kang says, queerness is not treated culturally. Instead, “all these topics seem much more politically charged.”

That’s a lesson many Maine journalists could take to heart regarding not only gay culture but other aspects of Maine’s shifting demographics. Somali immigrants, for example, are interesting at times other than just when they’re running for political office or being attacked by anti-immigration activists. The same goes for people of other cultures and backgrounds.

>> Farewell This will be my last Press Releases column; managing editor Deirdre Fulton will take over starting next month. I’ll leave you with a few goals to hold the Maine media to in the coming year:

1) Ask candidates for electoral office (at all levels) hard questions about specific issues, rather than allowing the candidates themselves to set the discussion agenda — thereby neatly avoiding any controversial issues or having to actually take positions on important questions of the day.

2) Allow politicians to change their minds. But don’t let them pretend they didn’t, nor that their new position is functionally the same as the old one. People grow, learn, and change. Expecting people to hold the exact same positions and beliefs forever in effect demands that people remain as misguided and unenlightened tomorrow as they were yesterday. But, when public figures change their minds, they should be able to, and asked to, explain why and how that happened.

3) Lastly — and this is to everyone, whether you work in the media or not — remember that government works for us. We own the desks and filing cabinets in City Hall and the State House, and the documents stored in them. We own the computers and the servers in government offices, and the information stored on them. If a government official wishes to keep something secret, she must prove that she is legally allowed to do so. The burden is not on us as the public to force openness on government, but on government — and its (our) workers — to lay themselves and their records open in exchange for the privilege of serving with the public trust.

Never Again Dept.: Learning from FairPoint's disasters

Published in the Portland Phoenix

Two bills before the Maine legislature seek to pry lessons from the hard time FairPoint has had taking over the former Verizon landline operations in Maine since 2009. Both step up government oversight, in hopes of preventing future debacles.

The first, LD 1761, could in fact be called the “FairPoint: Never Again” bill. It reads like an admission that the Public Utilities Commission’s process around the FairPoint-Verizon takeover was a disaster.

It would require state regulators to review all mergers and sales of companies earning more than $50 million a year not just to the standard of “doing no harm” to Maine consumers (incidentally, a standard current PUC chairman Tom Welch admits the FairPoint deal did not meet — a pity he wasn’t on the PUC when the deal was being considered) but rather such a deal must offer a “net benefit” to Mainers.

It would also specifically require regulators to consider any proposed deal’s impact not just on consumers and ratepayers, but also on workers at the company involved, as well as the state’s overall economic-development goals.

The move specifically anticipates the possibility that FairPoint might be looking for a buyer. “The hedge funds that own FairPoint are looking for an exit strategy,” says Matt Schlobohm, executive director of the Maine AFL-CIO. Unions are key proponents of this bill because of its enhanced consideration of the labor force in deals involving utility companies, which are often unionized, as FairPoint is.

If FairPoint does plan to sell — and there is a handful of potential buyers, mainly regional landline companies — “we’re not well prepared to get a good outcome” for Maine, Schlobohm says.

He fears a repeat of the FairPoint deal, in which regulators approved a deal that was questionable at best (see “A Bad Idea Triumphs,” by Jeff Inglis, February 29, 2008), with certain conditions imposed, but then over time waived many of those conditions one by one (such as benchmarks for rolling out higher-speed Internet service to more customers in Maine). 

“Why would the state not want to have more leverage” when dealing with big companies that have outsize impacts on Maine, both as utilities providers and major employers, Schlobohm asks.

The second bill is even more directly aimed at FairPoint itself. This one, LD 1479, could be called the “Oh No You Don’t, FairPoint” bill. It secures legislative oversight, review, and approval of any PUC ruling in response to FairPoint’s recent request for $67 million in support from Maine telecom consumers to subsidize its service to rural Mainers with no other options for phone connectivity. That amount would be paid by raising the Maine Universal Service Fund surcharge on all telecommunications bills (including Mainers who do not use FairPoint’s services) by as much as $5 per line per month. (See “FairPoint Wants Bigger Subsidies, From All Mainers,” by Jeff Inglis, January 3.)

And it comes at a time when FairPoint’s stock price is recovering — largely because of the prospect it may resume issuing dividends. Investors are certainly clamoring for that to happen; dividends were curtailed in the original deal by order of state regulators, and ultimately done away with because the company couldn’t afford them.

“There’s a pattern here,” says Schlobohm. “The company seeks resources . . . they figure out where to get them . . . they’re sent very quickly to Wall Street.”

While he admits this may not be the case now, he observes that “there’s not much trust built” between FairPoint and Mainers.

The union does support the idea of having phone service available to every Maine home, but is not sure that FairPoint’s request is the best or most efficient way to achieve that.

The online chef: Hungry for restaurant-quality scallops at home, one writer turns to YouTube

Published in the Portland Phoenix

A couple years back, I decided I wanted a new challenge in the kitchen. I love eating scallops at restaurants, and wanted to learn to make them myself. It turns out that home-cooked scallops are crazy-easy, super-delicious, and far cheaper than if you get them when you’re dining out.

But they’re intimidating: How do you get that crispy crust without burning the delicate mollusks? And how do you get them done just medium-rare in the middle, so they’re moist and flavorful, not rubbery and bland?

Recalling a previous year’s cooking lesson from Gordon Ramsay (he taught me how to cook delicious, tender scrambled eggs), I went to the same place I’d found Gordon: YouTube.

It’s truly surprising how much teaching is available on YouTube — and cooking lessons are no exception. I searched for scallops and came up right away with a 2008 video made by Bill King, who was then the executive chef at McCormick and Schmick’s seafood restaurants. (Searching for clams, mussels, oysters, or any other shellfish is similarly rewarding.)

King had a mouthwatering recipe for pan-seared scallops with sweet Thai chili and udon noodles. The video’s production value wasn’t that great, but I wasn’t there for a visual spectacle. The images and audio were clear, the instructions simple and basic, and the demonstration smooth.

I watched it, took notes, and watched it again. Then I went out and bought the ingredients: sweet Thai chili sauce, sesame oil, fresh sea scallops, and a couple packages of precooked udon noodles. (You can also get uncooked ones and make them yourself, just like pasta. I went for the easier option.)

It didn’t cost much; in fact, the scallops, which are so often expensive in restaurants, were under $7 for a solid handful that would serve two. (King’s example included three large scallops; I sometimes opt for four if they’re smaller.) The udon-noodle packets were a dollar apiece. The bottles of chili sauce and the oil were a few dollars each, but they’d keep and be available when I made more scallops later. Sure, it was more expensive than a couple of hamburgers, but not far off the price of steak, and much cheaper than lobster for two (even at today’s sea-bottom prices).

All that remained was to emulate a chef with formal training and decades of experience, in my own kitchen.

It didn’t quite work out the first time. Heeding King’s suggestion to have a very hot skillet, I ended up giving everything a nice layer of carbon. But I was learning, and I could see where I had gone wrong by comparing what happened in my pan with what happened in the video. I knew where I’d gone astray; in fact, I had indeed feared I was burning the noodles and the scallops while they were cooking. I hadn’t jumped in to lower the heat or stop the cooking earlier because I was on my first trial run and taking the directions very seriously.

I would not make that mistake again. It turns out — shocker! — that getting the cooking temperature right is crucial to preparing seafood properly (and, yes, other food too). My pan had been too hot, and I had left the noodles and scallops in the too-hot pan for a bit too long.

Still, I enjoyed the flavors, and was able to craft a plan for improving my performance next time.

And that’s perhaps the crucial rule of taking cooking lessons from YouTube: Test it out before you’re on the spot. If you’re cooking for a family gathering, or even just a hot date, don’t have that be the first time you’re trying to follow a video. Do it a couple times, even several, until you get it right.

Sure enough, a few days later, I was back at the seafood counter, buying more scallops, and then into the Asian section to grab some udon.

That time, I got the noodles right, but undercooked the scallops — I was too afraid of burning them and took them off the heat early. But I rescued them by returning them to the heat. (The removal-and-return to the pan meant the golden-brown crust wasn’t perfect, but I was making progress.)

It took a few more times — and a bad experiment cooking on a different stove at a friend’s house — before I felt confident in being able to make this dish reliably. And even now, I occasionally let them cook too long or too short, and have to make do with a substandard dish.

But it’s in my own home, with friends and family, and vastly cheaper than dining out. So I eat with relish! 

Make them yourselfHere’s the recipe; watch the video at: tinyurl.com/learntocookscallops.

Ingredients

>>Three to four sea scallops per person
>>One packet of pre-cooked udon noodles per person
>>Thai sweet chili sauce
>>Sesame oil

Procedure

>>Pat the scallops dry with a paper towel and then put them in a bowl with a small amount of Thai chili sauce atop each scallop, and a thimble-full or two of sesame oil apiece. Gently mix them with tongs or a spoon, to coat evenly. Set aside.
>>Heat a skillet on medium heat (ignore the video’s recommendation to have it very hot!), and lighly coat the pan with vegetable oil.
>>Put the udon noodle cakes in — only as many as will fit comfortably. Don’t pack them too close together. Now, don’t move them.
>>Cook them for 3-5 minutes, until you can see a golden-brown crust forming on the underside. You can peek carefully if you want to, or just flip them over and cook on the other side as well.
>>While they’re cooking on the second side, put a dab of the chili sauce on top, as well as a drop or two of sesame oil.
>>When they’re cooked through (they become more translucent and flexible), remove them from the heat and set them aside.
>>Wipe the pan with a dry paper towel, just to remove any debris or residue from the noodles.
>>Now return the pan to the heat (still medium) and put the scallops in.
>>Here’s the trick to getting the right crust on the scallops: Don’t touch them once they’re in the pan. Let them sit right where they are, sizzling, for about 2 minutes. (Three minutes if they’re much thicker than an inch.)
>>Then flip them over, revealing the very nice crust, and cook them for another two minutes on the other side.
>>Remove from the pan, and serve immediately.