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Posts Tagged → Arena Pharmaceuticals

Contrave Rejection and Obesity Drugs’ Future

Today’s a somber day for anyone looking to develop a weight-loss medication. Orexigen’s potential obesity drug Contrave has failed to win FDA approval, just as Arena’s Lorqess and Vivus’s Qnexa before it. In other words, none of the big contenders in the diet drug race we’ve been covering for nearly a year has panned out.

Contrave came into FDA decision-day with a a glimmer of hope behind it. Last December, an FDA panel voted in favor of approving Contrave, though they recommended that Orexigen conduct a clinical trial after approval to track the drug’s cardiovascular risk. In contrast, Lorqess and Qnexa hadn’t gotten a thumbs-up from the panel.

But the agency turned out to be more conservative than its advisory panel. In a so-called Complete Response Letter, FDA told Orexigen it needed to conduct that cardiovascular clinical trial BEFORE Contrave could be approved, not after approval. Orexigen’s stock fell over 70% on the news this morning. “Such a study would be huge, expensive, and would take years, and the request probably means that Contrave will never hit the market,” writes Forbes’s Matthew Herper.

So where do we go from here? I hesitate to say that the obesity drug field is dead. We’ll certainly continue to see scholarly papers about promising new obesity drug targets. But on the clinical side, the focus is going to have to shift away from weight loss to treating the conditions that tend to go hand-in-hand with obesity, like diabetes. That’s what could help tip the safety-efficacy balance in a way that leads to new drug candidates being approved by FDA. This is not a new idea- for instance, C&EN contributing editor Aaron Rowe has covered companies’ efforts to mimic bariatric surgery‘s beneficial effects on diabetes with a pill.

Pfizer is in Rowe’s story with a potential diabetes drug in clinical trials. The molecule targets an enzyme that reassembles triglycerides. One of its entries at clinicaltrials.gov says it all: “It is anticipated that PF 04620110 will have anti diabetic effects through inhibition of intestinal triglyceride absorption and potentially weight loss.” Pfizer exited obesity drug research in 2008. But it didn’t abandon efforts to treat some of the conditions that make obesity unhealthy. If targeting a certain enzyme happens to help with both diabetes symptoms and weight loss, so much the better. But weight loss isn’t the top priority.

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.

Abbott Takes Diet Drug Meridia (Sibutramine) Off The Market

A diet pill bit the dust today- the Food and Drug Administration has asked Abbott Laboratories to take its drug Meridia off the market in the U.S. Meridia, or sibutramine, was approved by FDA in 1997, but the company voluntarily pulled Meridia after FDA’s request, and is also halting sales of the drug in Canada and Australia. FDA’s request was based mostly on a large study from last fall called the SCOUT trial. The trial suggested that patients on Meridia had more cardiovascular events, such as heart attacks and strokes, compared to patients taking a placebo.

“Meridia’s continued availability is not justified when you compare the very modest weight loss that people achieve on this drug to their risk of heart attack or stroke,” said John Jenkins, M.D., director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research (CDER), in an FDA press release. Continue reading →

FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)

Yesterday brought yet another disappointment to the obesity drug development field- an FDA panel recommended rejecting Arena and Eisai’s potential diet pill lorcaserin (Lorqess) by a vote of 9 to 5.

The message from the panelists was that not enough data was available to assuage concerns about safety, as well as concerns about how the drug would work in a wider population.

This marks the second thumbs-down for a prospective obesity drug this year. Vivus’s drug candidate Qnexa received a ‘no’ vote from the panel in July.

Going into the yesterday’s panel, the mood wasn’t exactly sunny. As I wrote yesterday, the FDA briefing documents for lorcaserin contained an unexpected safety surprise. Continue reading →

Waiting For Arena, Thoughts On Meridia

Today the second of three potential drugs in the weight-loss race is in the hot seat- Arena Pharmaceuticals’ lorcaserin, which we recently learned will be called Lorqess, if approved. An FDA panel is meeting to decide whether it will recommend the drug for approval. I’m following two liveblogs of the panel, from Lisa LaMotta of Minyanville and Adam Feuerstein of TheStreet.com, and will post my thoughts on the aftermath tomorrow.

Obesity drug watchers are looking for clues about today’s panel based on one that happened yesterday- that was when Abbott Laboratories’ obesity drug Meridia, on the market since 1997, came under FDA’s microscope. Continue reading →

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 →

Eisai Will Sell Arena’s Obesity Drug Lorcaserin, Pending FDA Approval

Arena Pharmaceuticals has landed a partner for marketing its weight loss drug, lorcaserin- Japan’s Eisai. This makes Arena the first of the three big contenders in the obesity drug race to nab a partner.

In the deal, announced in the wee hours of this morning, Arena gets $50 million upfront from Eisai, and stands to make more in milestone payments upon delivering the product for launch time, if lorcaserin gets approved by the FDA. Still more additional payments, which could total up to $1.16 billion, will be tiered based on how well lorcaserin sells. Eisai gets exclusive U.S. rights to market the drug. Arena’s stock jumped this morning on the news.

You can get the specifics on the deal from Arena’s press release.

OK. You know it’s news when the company provides snazzy photos with the press release.

Arena said last month it planned to go it alone with lorcaserin if it couldn’t find a partner. But at the time, Leerink Swann analyst Steve Y. Yoo said in a report to investors that “the best source of funding, in our view, would be an upfront payment by a partner for lorcaserin.”

Well, now Arena’s got that cash. What does it mean for the obesity drug race as a whole?
Around the interwebs a few folks are wondering whether the terms of the deal still signal some caution on the part of Eisai.

My two cents are that in the obesity area, safety may reassure potential partners more than efficacy does.

As we wrote back in 2009, lorcaserin disappointed investors as early Phase III trial results came to light, because the compound met some but not all of FDA’s numerical weight-loss benchmarks.

But lorcaserin’s safety profile is very good. Perhaps it’s because Arena had the most to prove. Lorcaserin targets the same serotonin receptor as 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.

But lorcaserin is different from fenfluramine- it is more selective for one specific subtype of serotonin receptor and avoids the one that’s found in the heart. Arena has had to pay special attention to safety throughout lorcaserin’s development and they haven’t run into heart valve trouble.

Given the history of failures in the weight-loss drug field (Fen-Phen, rimonabant, etc), and given that a weight loss drug will be taken by many people who are otherwise healthy and may not even be clinically obese, it could be that safety will turn out to be king.