A hormone treatment based on technology used in Pfizer (PFE) Inc.’s failed inhalable insulin shows promise in fighting the leading cause of maternal mortality.
Six years after Pfizer pulled Exubera from the market at a cost of more than $2.8 billion, scientists at Melbourne’s Monash University are revisiting the inhalable technology to deliver a life-saving medicine to stop post-delivery hemorrhage.
The Bill & Melinda Gates Foundation is backing the effort to produce a better way to give oxytocin, a brain chemical that helps the uterus contract after birth and is sometimes referred to as the “love hormone” because of its role in orgasm and bonding. The project is one of several testing inhalations to deliver medicines, salvaging the know-how of a product that was taken off the market after just 14 months of lackluster sales.
“Exubera was the first generation,” said John Patton, one of the original inventors of Pfizer’s inhaled insulin technology system. “When you’re first, you take a lot of bullets. With the developments in the industry, it’s just a matter of time before we will be inhaling lots of medicine.”
The lead scientist for the Monash project, Michelle McIntosh, says her group plans to start testing a dry-powdered form of oxytocin by early 2014. Patton’s company Dance Biopharm Inc., is working on an inhaled insulin, as is Mannkind Corp. (MNKD), the biotech company founded by billionaire investor Alfred Mann.
Inhalations may not only avoid unpleasant injections. In the case of oxytocin, the need for refrigerated storage and sterile needles has limited the hormone’s use in Africa, where post-partum hemorrhage, the primary cause of almost a quarter of maternal deaths globally, is most frequent. Inhalers get around that problem.
“The injection works extremely well,” said McIntosh, the Monash scientist, in a telephone interview. “But in some parts of the world, the injection just isn’t always available.”
The Monash Institute of Pharmaceutical Sciences got more than $1 million from the Gates Foundation to develop a method for delivering oxytocin via a disposable inhaler that requires no specific training or refrigeration. Fewer than half of births in Africa are attended by someone skilled in midwifery, according to the World Health Organization.
Oxytocin is an essential medicine that countries should stockpile, says the WHO, which recommends the hormone be offered to all women during childbirth to prevent hemorrhage, or the loss of more than a pint of blood. The highest prevalence is in Africa, where about 10.5 percent of women encounter excessive bleeding after childbirth, according to the Geneva-based agency.
Used preventively, oxytocin can cut the rate of post-delivery bleeding complications by half by causing muscles in the uterus to contract, closing off damaged blood vessels. McIntosh’s group plans to start testing their product in 18 healthy volunteers in Australia by early next year, she said.
Doctors already use inhaled products to address respiratory conditions such as asthma and influenza. The delivery system also has potential to help with weight loss and pain, according to Dance Biopharm’s Patton.
The challenge for scientists is to come up with a dry-powdered formulation of liquid drugs that can be absorbed into the bloodstream via the tiny blood vessels in the lungs without losing potency.
“The door is open -- it’s the engineering that needs to be done to get these aerosols in,” Patton said. His former company, Nektar Therapeutics (NKTR) Inc., worked with Pfizer on Exubera until 2007. The 66-year-old scientist is now chief executive officer of Dance Biopharm in San Francisco.
In the case of insulin, the hormone diabetics need to prevent sugar from pooling in their blood, the goal for a company like Valencia, California-based Mannkind is to make the inhaled drug better than the shot.
Mannkind, which has seen its stock price more than double this year, is slated to report results of late-stage tests in August involving Afrezza, an insulin taken at mealtime from a whistle-sized inhaler. Mannkind rose 2.3 percent to $5.31, the highest since Feb. 8, 2011, in Nasdaq trading today.
The product has the potential to “revolutionize the treatment of diabetes” because the inhaled hormone acts faster to control blood-sugar levels, Chief Financial Officer Matthew Pfeffer said in a telephone interview.
Pfizer’s Exubera, by contrast, “was relatively crude by today’s standards,” he said. “From the perspective of a diabetic, the only thing it offered was a way to avoid injection.”
The science may be especially useful for drugs based on short chains of amino acids, known as peptides, which help regulate bodily functions such as metabolism. Peptides are denatured by gastric enzymes, making them difficult to administer in pill form, according to Patton.
“The deep lung is the one place that can get these things into the body without using a needle,” he said.
That advantage is what first persuaded Pfizer in 1995 to partner with Patton’s company on Exubera. But patients were dissuaded from switching over because the product was bulky -- about the size of a hairspray can -- cost more, and worked no better than its injected predecessor.
Pfizer is no longer developing inhaled insulin. The company “will continue to evaluate inhaled approaches in inflammatory conditions affecting the lungs,” Trupti Wagh, a Singapore-based spokeswoman, said in an e-mail. At the time, Eli Lilly & Co. (LLY) and Novo Nordisk A/S (NOVOB) also dropped experimental inhaled insulins.
“When Exubera was pulled, it was a huge hit to the whole inhaled-drug industry,” Patton said. “Today, with developments from groups such as Mannkind and the Australian oxytocin research team, it’s all coming back.”
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