BioSpace’s Favorite FDA Tricks Or Treats

October 24, 2014

By Riley McDermid, BioSpace.com Breaking News Sr. Editor

Feeling spooky yet? In the third of our four Halloween-themed features this month, BioSpace took a lighthearted look at both the ghoul and the fairy godmother of the biotech industry: The U.S. Food and Drug Administration. Nothing can make industry executives feel more frightened—or enlightened—than a solid decision from these regulators! We’ve compiled some of our favorite tricks and treats dispensed by the FDA lately.

FDA Tricks

The criteria for making it onto our Tricks List was fairly simple: If a drug has been denied more than once, it’s already in the running. Three times, however, it’s pretty clear it is dead in the water—and all the trials and clinical results go down with it. Below are four of the most notorious denials in recent memory.

1. Vascepa from Amarin

 

The third time was no charm for Amarin's fish-oil pill Vascepa, after the FDA finally put the kibosh on the prescription drug in September. The company finally gave up after the Office of New Drugs (OND) within the FDA denied Amarin's appeal of FDA's rescission of agreement.

News of the denial sent shares of Irish-based Amarin plummeting 23 percent. Amarin has admitted in the past that it will be an uphill battle to gain SPA agreement reinstatement, but issued a statement saying continuing evaluation of the drug is in the interest of public health. The company continues to wait on a verdict from the FDA on the pending ANCHOR supplemental new drug application (sNDA). Vascepa remains FDA approved and marketed for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia.

2. Flibanserin from Sprout Pharmaceuticals
The “female Viagra” pill flibanserin from Sprout Pharmaceuticals found no joy with the FDA, despite a lot of media hype about its potential market share and a vigorous publicity campaign. With the proposed trade name of Girosa, Sprout attempted to take the pill through the FDA approval process three times—and was shot down each time. Still, the company has said it will continue to fight to win federal approval for the drug which it says treats a specific type of female sexual dysfunction known as hypoactive sexual desire disorder, or HSDD.

Boehringer Ingelheim Pharmaceuticals was initially backing the “little pink pill” but bowed out in the fall of 2010 after negative feedback from an FDA advisory panel. Sprout, a spinoff from Slate Pharmaceuticals, then snapped up the rights to flibanserin and has been attempting to meet the FDA’s demand for more extensive clinical testing of the drug.

3. AVEED from Endo Health Solutions Inc.

 

 

Injectable testosterone drug AVEED could not catch a break from regulators at the FDA for the first three times it attempted approval, though it did win the gold star the fourth time around. For years Endo Health Solutions brought Aveed before the FDA’s overseers and each time the answer was the same: Endo's proposed plan for managing the risks associated with the drug was insufficient.

AVEED, which is made of testosterone and castor oil, is designed to boost testosterone in patients with low levels of the hormone. It significantly expands treatment options for men with low testosterone, which can affect bone growth, muscle function and bulk. However, the type of oil used had the FDA concerned that it might eventually cause blood clots of clogged vessels in the lungs.

The Food and Drug Administration has for the third time refused approval to Endo Health Solutions' injectable testosterone drug AVEED, pressing for a still better plan to manage the risks associated with the drug. However, after providing the FDA a comprehensive medication guide and a risk mitigation strategy, the regulator finally signed off on AVEED last spring—letting Endo breathe a long-awaited sigh of relief that all those clinical trials weren’t for naught.

4. Rextoro from Clarus Therapeutics
The rejection of Clarus Therapeutics’ oral testosterone drug Rextoro in September was a double whammy for the company: Not only did it mean the firm would likely miss out on the booming “low-T” market, it also likely torpedoed its hopes for an initial public offering later this year.

The FDA's urologic and drug safety committees voted 18-3 with one abstention to deny Clarus’s application, issuing a scathing rebuke to the company for not allaying fears that the testosterone therapy can lead to elevated risks of heart attack and other cardiovascular events. It added that Clarus had provided incomplete data from the drug's two Phase III trials—a tricky subject these days, as low testosterone drugs have been under fire for a potentially increased risk for cardiac trouble and the ability to be prescribed for any off-label complaint.

For now, Clarus will need to get its ducks in a row on Rextoro and likely sit on the sidelines of the most vibrant biotech IPO market since the early 1990s. Because the drug is the firm’s biggest catnip for investors, its denial and a failed $86 million IPO earlier this year mean it could be a rough few financial quarters for the Clarus.

FDA Treats

Similarly, getting onto our FDA Treats roster was an easy task: If a drug showed significant benefit across all patient sectors for a chronic public health problem, it was pretty much a shoo-in. Since we don’t engage in price war debates here at BioSpace, we have included some of the pricier drugs approved in 2014, but their contribution to the wellbeing of mankind makes them stars—and the FDA star-makers.

1. Harvoni from Gilead Sciences

 

 

The FDA took a huge leap towards curing hepatitis C when it approved the first once-a-day pill, Harvoni, on Oct. 10. Manufactured by Gilead Sciences . Harvoni is a cocktail of ledipasvir and sofosbuvir (known under the brand name Sovaldi). It has now been cleared for use in the main subtype of hepatitis, called genotype 1, which accounts for more than two-thirds of the nation’s cases.

Gilead has had high hopes for Harvoni, after clinical trials found that over 90 percent of the patients treated with the drug had no detectable virus in their blood three months after treatment was ended. In medical parlance, that is effectively a cure.

Harvoni combines the NS5A inhibitor ledipasvir with the nucleotide analog polymerase inhibitor sofosbuvir, approved under the tradename Sovaldi in December 2013. Harvoni’s efficacy has been established in patients with chronic hepatitis C virus (HCV) genotype 1 infection, with a treatment duration of eight, 12 or 24 weeks depending on prior treatment history, cirrhosis status and baseline viral load. Eight weeks of treatment with Harvoni can be considered for treatment-naïve patients without cirrhosis who have baseline HCV viral load below 6 million IU/mL.

2. Farxiga from AstraZeneca and Bristol-Myers Squibb
The U.S. agency started the year off with a bang on Jan. 8 when it approved AstraZeneca and Bristol-Myers Squibb Company's Farxiga (dapaglifozin) to improve glycemic control in adults with type 2 diabetes. The drug, along with diet and exercise, was evaluated in 16 clinical trials of more than 9,400 patients with type 2 diabetes—and Farxiga was linked to improvements in HbA1c levels across the board.

Perhaps most importantly, the GLT2 inhibitor is exciting as a possible next-generation treatment because it focuses on restoring kidney function, as opposed to the liver and pancreas. In addition, it has the upside of goosing weight loss, something competitors like Januvia have not been able to crack. The FDA had previously had an advisory panel reject the drug because of concerns of it might be linked to elevated bladder and breast cancers. The drugmakers obviously allayed those fears successfully and Forxiga is now green-lit for market.

3. Imbruvica from Johnson & Johnson

 

 

Johnson & Johnson won the prize for fastest approval in this article, after its cancer drug Imbruvica received accelerate approval in February. Imbruvica is designed to treat chronic lymphocytic leukemia (CLL), the most common form of adult leukemia, and its success rate had the FDA rushing to push it out to critically ill patients and their clinicians. At only the midway point of its first study, Imbruvica was already showing a positive response rate of 71 percent, a number that evolved into progression-free survival of 75 percent after 26 months.

Those metrics were so impressive that Wall Street analysts quickly projected Imbruvica could eventually capture $7 billion in market share as it treats the type of non-Hodgkin lymphoma. CLL is a rare blood and bone marrow disease that boosts an increase in white blood cells called B lymphocytes, or B cells, which tips the disease into progression. Imbruvica combats the disease by blocking enzymes that help cancer cells grow and divide—and with a success rate like that, approval was a no-brainer for the FDA

4. Afrezza from MannKind Corp.

 

 

For once, the third time really was the charm for California biotech company MannKind's new inhalable insulin device Afrezza when the FDA gave it the go ahead on June 27. The ultrarapid insulin is delivered via Afrezza in powder form as a pre-meal insulin for adults suffering from type 1 or type 2 diabetes. It had been rejected by the FDA twice before because the regulator was not convinced clinical study data showed conclusive safety and effectiveness, but MannKind eventually assuaged those worries.

Now the therapy, which focuses on leveling out post-meal blood sugar spikes, is getting ready to be rolled out to wider market as a supplement to existing insulin treatments. Delivered via an inhaler dubbed the Dreamboat, Afrezza peaks within 12 to 15 minutes compared to other methods that take 20 minutes to start working then don’t peak for at least two hours. Even more appealing? The fact that Afrezza is out of the system in an hour, as opposed to a five hour lag time with other therapies. That lung-to-bloodstream rapidity has had MannKind laughing all the way to the bank since June.

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