2014 Pipeline Report: The Sprint to Value - Pharmaceutical Executive


2014 Pipeline Report: The Sprint to Value

Pharmaceutical Executive

Obesity and Diabetes: Two Birds One Stone

There's still a lot to be said for the American Dream (assuming it hasn't succumbed to heart failure), but the American Diet is not worthy of admiration. "Other countries are starting to live like us...and die like us," said Dean Ornish, president of the Preventative Medicine Research institute, during the Cleveland Clinic's recent conference on obesity and diabetes. "Weight loss can reverse heart disease, prostate cancer, Type 2 diabetes" and other conditions, he said.

FDA has already approved two new obesity drugs—Arena/Eisai's Belviq, and Vivus's Qsymia—the first FDA approvals for the condition in over 15 years, but given the size and extent of the health problem, not to mention the cost, better treatments and devices are needed. Future therapies will attempt to target the "microbiome" or gut flora, to change the way that food is synthesized in the gastrointestinal tract. Anthony Viscogliosi, principal at Viscogliosi Brothers, a New York-based VC/private equity firm, said he wants to invest in "meds that inhibit fat syntheses...that can change the microbiome to turn sugar and fat into water."

Next-gen probiotics and nutraceuticals could potentially impact the microbiome—scientists have developed a trimethylamine N-oxide (TMAO) assay that detects TMAO—a microbial byproduct of intestinal bacteria—in the blood, that is associated with a 2.5-fold increase in stroke and heart attack. But the microbial genome, or microbiome, contains about 3.3 million genes. Compared with what we still don't know about the human genome, and its 23,000 genes, an active therapy for a specific microbiome target probably won't emerge in the next couple of years. However, Steve Nissen, the Cleveland Clinic's department chair of cardiovascular medicine, told conference-goers that the TMAO biomarket "could take off in 2014...and drugs will follow."

In the shorter term, Orexigen Therapeutics may be the most promising and lucrative late-stage oral medication for the treatment of obesity. In January, FDA asked for additional cardiovascular outcomes data and proposed a resubmission procedure for Orexigen's Contrave, a naltrexone/bupropion combination pill, and the company expects to resubmit to FDA by the end of this year. Orexigen appears to have faired better in Europe; EMA has accepted its submission under the centralized procedure, and Orexigen expects approval in the second half of 2014. Despite a similar efficacy in comparison with Belviq and Qsymia, naltrexone/bupropion is still getting blockbuster nods. Thompson Reuters projects roughly $1.1 billion by 2019, and Credit Suisse corroborates that approximation, putting 2020 sales at $1.1 billion. Credit Suisse predicts very similar sales for both Belviq and Qysimia, which suggests the level of need in the market, or opportunities for the products to differentiate from one another, or both.

Novo Nordisk is preparing to file a 3-mg version of its GLP-1 liraglutide (aka Victoza) for an obesity indication in the United States, and has entered Phase III trials in over 20 countries for that indication. In the United States, Novo will file by the end of this year, and expects to get an approval in 2014. The company may try to best the new raft of obesity treatments by maximizing the label; in June, Novo completed a Phase III trial studying obese patients with sleep apnea. Clinical studies indicate that liraglutide at 3 mg could bring down body weight by an average of eight percent, a slight improvement on Belviq and Qysmia, but liraglutide is an injectable, not a pill, and it's expected to be costly. Gideon Heap, an analyst with Decision Resources, says he likes liraglutide in obesity for the following reasons: "In theory, [liraglutide] will avoid any of the CNS side effects that trouble a lot of physicians in obesity, and Novo also has some good trial designs going," says Heap. "They are developing it with a Phase II trial that attempts to show prevention of the onset of Type 2 diabetes. If that gets a positive outcome, I think it would represent a strong bargaining chip for getting better reimbursement [over Belviq and Qsymia]." Credit Suisse forecasts have liraglutide's obesity indication adding another $500 million a year to the increasingly lucrative Victoza franchise, by 2019. Decision Resources predicts roughly $800 million by 2019, with a launch late next year.

Device Alert
Since 1997, there have been 10 new classes of diabetes drugs, and yet, many patients still aren't able to keep their glycemic levels under control. Takeda hopes to bring an 11th class of drug to market with its TAK-875 compound, a GPR40 agonist. Currently in Phase III testing, TAK-875 is going head-to-head against Januvia, and could potentially launch in 2015 or 2016, according to Heap. TAK-875 "is causing a bit of excitement because it's showing good efficacy while maintaining a high level of safety, of a kind you would see with the DPP4 inhibitors," says Heap. "It's as efficacious as sulfonylurea, but in Phase II showed low rates of hypoglycemia, and crucially, it doesn't appear to induce any kind of weight gain."

Al Mann hopes to bring a new drug delivery device to market; this time he's more hopeful than ever. In September, Mann personally assured Pharm Exec that Afrezza, a product that needs little introduction, will receive its long-awaited FDA approval in April—if it isn't approved somewhere else first. Analysts seem to agree that MannKind's inhalable insulin will indeed get approved, but a lingering question remains: will patients want to use it? "There aren't a lot of patients out there demanding an inhalable insulin," says Heap. "Possibly, the developers of these [inhalation] devices are a bit carried away with how important they think that is." After completing two 24-week Phase III trials with its next-gen Dreamboat inhaler device, MannKind resubmitted with FDA in October. Thomson Reuters is predicting over $2 billion in sales, but Kiran Meekings, a consultant at the Thomson Reuters Life Sciences team, isn't so sure. She worries about the potential for adverse pulmonary effects over the long term. MannKind's clinical work has attempted to mitigate concerns about lung function associated with chronic use of an inhaled insulin, and Mann says Afrezza "is not in the lungs very long, we go quickly through the membrane into the blood, with no accumulation." Meekings says MannKind's pulmonary safety study results "weren't necessarily cause for concern...but it's something that needs to be monitored."

Finally, Eli Lilly and Boehringer Ingelheim are attempting to bring a biosimilar insulin—the oldest biologic drug—to market. The European Medicines Agency (EMA) accepted the companies' long-acting insulin glargine biosimilar submission in July, and the product is in Phase III in the United States. Insulin glargine, also known as Lantus, is Sanofi's top seller, with over $6 billion in sales last year. Credit Suisse is bullish on the biosimilar version, with predicted sales topping $1.2 billion by 2019, not bad for a copycat. Thomson Reuters is more conservative, with a forecast of $415 million in annual sales for the biosimilar by 2019. Sanofi, for its part, is rushing forward on U300, a reformulated insulin glargine; the company said during a 3Q conference call that it would file in the United States and Europe during the first half of 2014. That product's new attributes, according to Sanofi, are fewer incidences of hypoglycemia, and a smaller volume of subcutaneous injection compared with Lantus. Incidentally, Lantus loses patent protection in 2015. Novo Nordisk, the biggest seller of insulins worldwide, hopes to wrest back marketshare from Sanofi, but probably won't get Tresiba approved in the United States before 2016, at the earliest. Thomson Reuters estimates the new and improved version of Lantus will earn $1.1 billion by 2019, a fraction of Lantus's current annual sales.


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