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Posts Tagged → Contrave

Takeda Keeps On Truckin’ With Obesity Drug Research

This year’s additions to the pile of setbacks in the obesity drug arena are enough to make anybody wonder whether big pharma companies will continue to invest in the field (was it already two years ago that Pfizer exited obesity research entirely?!). But news today of a pact between Takeda and Sanford-Burnham Medical Research Institute suggests the Japanese drug maker is in it for the long haul.

Takeda’s agreement with Florida Hospital and Sanford-Burnham Medical Research Institute creates a partnership to evaluate potential new obesity drug targets.

Today’s deal is the latest in a string of obesity-related investments for Takeda. Haystack readers may recall that Takeda is Orexigen’s partner for the development of Contrave, the weight-loss drug that is awaiting a decision from FDA in the wake of a thumbs-up from the agency’s advisory panel. The company also has a stake in peptides from Amylin Pharmaceuticals as potential obesity treatments, and it is conducting clinical development in Japan for Alizyme’s lipase blocker cetilistat, a next-generation pill to Xenical (orlistat), the drug sold over-the-counter as alli.

Takeda’s interest in obesity makes sense given its strong history with type 2 diabetes drugs, a class with close ties to the obesity area. A quick look at Takeda’s pipeline is a whirlwind tour of diabetes drug targets, like glucokinase activators and dipeptidyl peptidase-4 inhibitors. The company has also discovered a protein, TGR5, that could be a target for drugs that mimic gastric bypass surgery‘s ability to control diabetes. And they are behind Actos, the well-known diabetes medication which shares its mechanism of action with Avandia. Unlike Avandia, Actos remains on the market, although FDA is currently investigating its safety.

Will Takeda’s strategy pay off? Time will tell- beginning with FDA’s official decision on Contrave by the end of January.

Good News for Contrave, Qnexa Could Be Next

Apparently, third time’s a charm in the obesity drug world. Yesterday afternoon, an FDA advisory panel recommended approving Contrave, an obesity pill being developed by Orexigen Therapeutics and Takeda. The positive vote came just months after two other obesity drugs, Vivus’ Qnexa and Arena Pharmaceutical’s Lorqess, were rejected.

There are plenty of caveats to the good news. First, FDA doesn’t always follow the advice of its advisory committees, although most analysts seem confident Contrave will make it onto the market. But Orexigen and Takeda will likely need to conduct a large, post-approval study to track cardiovascular issues, the details of which would be hammered out with FDA.

Second, excitement over the next pill for obesity should be tempered with the reality that Contrave has shown only minimal weight loss. Contrave is a combination of two already-approved drugs, the antidepressant buproprion and the addiction treatment naltrexone.

All that said, Orexigen stands to collect more money from Takeda if Contrave makes it to the finish line. Takeda paid just $50 million upfront to license the obesity drug, and will take on the lion’s share of the costs of a post-approval study.

The thumbs up for Contrave could also be good news for Vivus’ Qnexa, also a combination of two existing drugs (phentermine and topiramate). In July, an FDA advisory committee, concerned about the lack of long-term safety data for the drug, voted against its approval. FDA backed up that decision in October, issuing a complete response letter (its version of a rejection) citing birth defect worries and cardiovascular risks.

But yesterday’s panel was mainly focused on the cardiovascular risks associated with Contrave, and Qnexa is a cleaner drug on that front. One panel member, University of California, Davis, neurologist Michael Ragowski, even said he’d rather prescribe Qnexa versus Contrave. Vivus plans to submit a formal response to the CRL later this month, and FDA would provide its feedback in January. If all goes well, Vivus could gain approval for Qnexa in the second half of 2011, analysts say. Investors seemed optimistic on its chances, as Vivus’ stock is up over 20% in pre-market trading.

Orexigen is holding a conference call at 4:15pm this afternoon, to discuss the panel. If anything interesting comes out of it, we’ll be sure to update readers!

Orexigen And Takeda’s Contrave To Face FDA’s Panel Tuesday

Image: C&EN

Today FDA released its briefing documents for Orexigen and Takeda’s experimental obesity drug Contrave. And they’ve got more than one news outlet wondering whether the third time will be the charm in the obesity drug race. On Tuesday, FDA’s outside advisers will meet to review the potential drug and make recommendations on whether to approve it. You can read our ongoing coverage of Contrave as well as Arena’s Lorqess and Vivus’s Qnexa, the other two obesity drug candidates FDA reviewed, here.

At first glance, the documents don’t contain any big surprises in terms of safety or efficacy. And Orexigen’s had time to learn from what happened at the Lorqess and Qnexa panel meetings.

That said, Adam Feuerstein makes an interesting comparison- to Meridia, Abbott Labs’ diet pill that was pulled from the market this fall because of its cardiovascular risks. We’ve known that Contrave can raise blood pressure, but the memory of Meridia may influence some of FDA’s outside experts.

Contrave’s cardiovascular risk profile somewhat resembles Abbott Lab’s Meridia, which was recently pulled off the market after a September advisory panel meeting. Eight of the 10 experts who will be reviewing Contrave Tuesday voted to recommend Meridia’s withdrawal from the market due to the drug’s cardiovascular risks. These eight experts are the people Orexigen needs to be most worried about Tuesday.

An analyst at Rodman & Renshaw in New York had similar concerns in an interview with Bloomberg.

“They may have to do a thorough cardiovascular study before approval,” said Elemer Piros, an analyst at Rodman & Renshaw in New York, in a telephone interview today. “The clear precedent is Meridia. It’s so fresh in our minds that I don’t think the FDA wants to embark on a public experiment in an uncontrolled setting without this information.”

So if more studies will be needed, it’s a good sign that Leerink Swann analysts Joshua Schimmer and Steve Yoo are impressed with Orexigen’s long-term safety strategy, according to a note sent to investors.

While no FDA panel is without risk and the track record of obesity drugs at the Endocrine Division is unquestionably poor, we have been impressed with OREX’s strategic approach to tackling Contrave’s safety-issues head on and its rational explanation for a post-approval study commitment.

That’s important because at least some of what sank Vivus’s Qnexa at its FDA advisory panel evaluation was a desire for more long-term data.

But at the end of the day, panelists who voted ‘no’ felt like more long-term safety data was in order. From Feuerstein’s liveblog:
one of the “no” votes says obesity is a chronic disease, so tell me what happens to patients as they stay on the medication for years.

Like Qnexa, Contrave is a combination of two drugs that are already FDA-approved. But it remains to be seen whether Orexigen has learned enough from Vivus’s experience to put together a convincing case for the FDA panel.

Options abound for following Tuesday’s meeting. Lisa LaMotta, now at Elsevier Business Intelligence, will be covering the panel live. Follow her @BioWriterChik. Feuerstein will as well, @adamfeuerstein. And FDA will webcast the panel here.

FDA Rejects Vivus’s Obesity Drug Qnexa

As was widely expected, the Food and Drug Administration has rejected Vivus’s experimental weight-loss drug Qnexa, making it the second obesity drug in a week to be turned away by the agency. On Saturday, Arena Pharmaceuticals said it had received a complete response letter (CRL) for  its obesity drug Lorqess (lorcaserin), based largely on worries that the drug caused tumors in rats.

The biggest concerns in Vivus’ CRL were around birth defects and cardiovascular risk. Vivus had already submitted a plan to keep tabs on pregnancy and birth defects after the drug was approved, and the agency seems to want to continue evolving that monitoring strategy. FDA also wants data showing that the drug’s propensity to raise heart rate does not lead to an increased risk of cardiovascular events. If eventually approved, FDA said Qnexa would be considered a controlled substance along the lines of Xanax and Valium.

The good news  is that Vivus says it doesn’t believe it needs to generate any new clinical data to fulfill FDA’s requests. Further, the agency didn’t ask any questions about the drug’s ability to induce weight loss. In a conference call with investors this morning, Vivus CEO Leland Wilson said it would take the company about six weeks to prepare its response to the CRL, and depending on how FDA classifies the application, the drug could be reviewed two-to-six months after the submission. Shares of Vivus were up over 30% in pre-market trading.

As a reminder, Qnexa is the only drug in the three-way obesity race to lack a partner. Arena has licensed Lorqess to Esai, and Takeda has bought into Orexigen’s Contrave.

Qnexa is a combination of two drugs that are already FDA-approved: it’s a combination of topiramate, an antiseizure medication that enhances feelings of fullness, and phentermine, the “Phen” part of Fen-Phen, which was not linked to heart valve defects.

When FDA posted briefing documents in advance of the Qnexa panel meeting, we learned that the agency had no problem with Qnexa’s ability to help patients lose weight. But the committee had safety concerns in five areas: effects on pregnant women, cardiovascular risks, psychiatric events, cognitive events, and metabolic acidosis. Last July, an FDA panel thought that Vivus needed more long-term safety data on Qnexa and voted not to recommend the drug for approval. (Seven panel members voted for approval but nine recommended against approval.)

Arena’s Weight-Loss Pill Lorqess (lorcaserin): Waiting For FDA

Tomorrow is the deadline for the Food and Drug Administration to make a decision about whether or not to approve Arena Pharmaceuticals’ experimental obesity drug Lorqess (lorcaserin). In advance of the decision I’ve recapped some Lorqess news and information from the last several months. We will update you when FDA’s decision comes in.

Of the three potential new diet pills racing to reach the market, Lorqess (lorcaserin) is the only one where the active ingredient is a completely new molecule. Its competition, Vivus’s Qnexa and Orexigen’s Contrave, are both combinations of drug molecules that have already been FDA-approved for other conditions.

Lorqess targets an appetite-suppressing serotonin receptor located in the brain. It’s the same receptor that was targeted by fenfluramine, an ingredient in the infamous Fen-Phen obesity drug combo. Fenfluramine was associated with heart valve damage and a fatal lung disorder- it was pulled from the market in 1997.

Lorcaserin is different from fenfluramine- it is more selective for the specific subtype of serotonin receptor found in the brain and avoids the one that’s found in the heart. Arena’s idea behind Lorqess was that a more selective drug might have the weight-loss benefits with fewer side effects. Arena has had to pay special attention to safety throughout lorcaserin’s development and they haven’t run into heart valve trouble.

In July, Arena landed a partner for marketing Lorqess- Japan’s Eisai.

But last month, when an FDA panel met to discuss Lorqess, the outcome was disappointing for Eisai and Arena. Background materials for the panel session raised questions about malignant tumors that occurred in rats given high doses of lorcaserin. And the panel itself recommended that FDA not approve Lorqess by a 9 to 5 vote. The panel decided not enough data was available to assuage concerns about safety, and was also concerned about how the drug would work in a wider population than was tested during clinical trials. In the aftermath of the panel recommendation, analysts suggested a number of pieces of data that Arena could provide to improve its overall package of information about Lorqess, and thus the drug’s chances. But many of the suggestions, which included a detailed study of the mechanism behind the rat tumors, and a Phase II proof of concept trial of lorcaserin and phentermine in diabetics, take years, not months.

Today’s FDA decision is sure to set the tone for the next couple of months, since Lorqess is the first of the three big contenders to be judged. FDA could decide to ask for more data on Lorqess, or make a decision outright. Stay tuned.

Orexigen Partners With Takeda for Potential Obesity Drug Contrave

This morning Orexigen Therapeutics became the second of the three leaders in the obesity drug race to partner with a larger company. They’ve successfully courted Takeda, which now gets exclusive marketing rights to obesity drug Contrave in the U.S., Canada, and Mexico, if the drug gets regulatory approval. Orexigen’s shares soared on the news, first released in the pre-dawn hours this morning.

In the deal, Orexigen gets $50 million upfront from Takeda and could nab up to $1 billion more, depending on whether Contrave meets certain regulatory and sales milestones. Further details about the agreement are available on an Orexigen press release.

Contrave refresher: Contrave is a combination of two drugs already on the market: naltrexone, which is typically used to manage alcohol or opioid dependence, and the antidepressant bupropion. Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.

In July we covered the first partnership deal in the obesity drug race, that of Eisai and Arena Pharmaceuticals, which is developing the obesity drug candidate lorcaserin. It’s worth stepping back to compare and contrast the deals. Continue reading →

Orexigen’s Obesity Drug Candidate Contrave Gets 12/7 FDA Review Date

Mark December 7, 2010 on your obesity drug watch calendar. Orexigen Therapeutics has just announced that on that date, an advisory committee at FDA is tentatively set to review the company’s new drug application for its obesity drug candidate, Contrave.

Symbolically, I can imagine folks might’ve preferred a different date. December 7, is, after all, best remembered as a day that will live in infamy.

But the December date is good for Orexigen in other ways. It’s much later than July 15, when FDA is set to evaluate Vivus’s experimental obesity drug Qnexa. We’ve already written about Orexigen’s opportunities to learn from its competitors.

Here’s more of what we’ve written before about Contrave.

Contrave, like Qnexa, is a combination of two drugs already on the market, bupropion and naltrexone. As we explained in 2009, Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.

Orexigen Gets Review Date For Obesity Drug Candidate Contrave

We now have the final FDA review deadline date for all three of the biggest contestants in the obesity drug race. Today Orexigen Therapeutics announced that FDA has assigned a January 31, 2011 Prescription Drug User Fee Act (PDUFA) date for the firm’s obesity drug candidate, Contrave. This is right about when people expected the date would be, given that Orexigen filed for the drug’s approval back in April. The PDUFA date is the goal date for FDA to finish reviewing the company’s new-drug application. This is when folks will be watching for approval decisions.

Orexigen’s two biggest competitors are Arena’s lorcaserin and Vivus’s Qnexa. Both of the other drugs’ FDA review deadlines are in October of this year. But as we’ve written before, if you’re first to the finish line, you don’t have the opportunity to learn from what came before.

This is the part where I say “let’s not get carried away, here”:
Anywhere from zero to all three of these experimental drugs could be approved by FDA. It’s all about the balance between efficacy and safety.

And none of the three companies developing the drug candidates has found a bigger company to partner with them on the project. Though the big companies might be waiting for a bit more clarity on the drugs’ approvability, as Leerink Swann analyst Steve Yoo said in a note to investors last March.

More reading on Orexigen here.

Orexigen, Contrave, And Obesity Firsts

As I follow the race to bring a new drug for obesity to market, I have to wonder- is being first necessarily best? Biopharmaceutical company Orexigen doesn’t seem to think so. Yesterday the firm laid all its cards on FDA’s table as it filed for approval of its experimental diet medication, Contrave. Assuming FDA accepts the application, that means we should be hearing whether the agency gives Contrave the thumbs up by about January 31, 2011.

That’s a few months later than Vivus’s Qnexa and Arena Pharmaceuticals’ lorcaserin, two other drug candidates for obesity.

Contrave, like Qnexa, is a combination of two drugs already on the market, bupropion and naltrexone. As we explained in 2009, Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.

The whole race reminds me a little bit of grad school. I used to work in an organic chemistry group that specialized in total synthesis. While it’s true that I learned the value of being first to finish a molecule during those years, I also gained an appreciation for the fine syntheses that, though not first to the finish line, had learned something from others’ work and had a twist that made them valuable. Maybe learning from the earlier two horses in this race as they navigate FDA is part of Orexigen’s strategy.

Vivus Gets Obesity Drug Review Date

Obesity drug watchers, mark your calendars. In recent weeks, companies with experimental weight loss drugs in late-stage clinical trials have announced some important dates in the Food and Drug Administration’s evaluation process.

Save the dates:
July 15- Vivus Inc. has announced that an advisory committee at FDA is tentatively set to review the firm’s new-drug application for obesity drug candidate, Qnexa, at a meeting on this date.

October 22- Arena Pharmaceuticals has announced that this is the Prescription Drug User Fee Act (PDUFA) date for the firm’s experimental lorcaserin obesity medication. The PDUFA date is the goal date for FDA to finish reviewing the company’s new-drug application. This is when folks will be watching for approval decisions.

October 28- This is the PDUFA date for Qnexa.

A third company, Orexigen Therapeutics, has its Contrave obesity drug candidate in late-stage clinical trials, but has yet to file a new-drug application with FDA. The three companies are the furthest along in the race to bring new obesity drugs to market.

As we reported nearly a year ago, chemically speaking, only lorcaserin is actually new. The compound is more selective version of fenfluramine, better known as the “Fen” portion of the infamous blockbuster weight-loss drug combo Fen-Phen, which was pulled from the market. Lorcaserin is designed to avoid one of the serotonin receptors fenfluramine targeted- an activity that Arena believes was responsible for the heart valve defects Fen-Phen users experienced.

Qnexa contains drugs that are already FDA approved: it’s a low-dose combination of topiramate, an antiseizure medication that enhances feelings of fullness, and phentermine, the “Phen” part of Fen-Phen, which was not linked to heart valve defects.

The Fen-Phen craze teaches us that there could be millions of prescriptions for an FDA-approved weight-loss drug. Not all of them will be written for patients who are obese. Expect FDA to weigh drugs’ efficacy and safety very carefully.