industry dogged by safety concerns, a private US company is betting on a new
approach to deliver just such a pill that could end up being the first
billion-dollar diet drug.
Initial trials show that Zafgen Inc., run by a
former Novartis AG executive, might have an edge over its competitors,
especially since its experimental drug has so far not demonstrated any major
safety concerns. Or, as one doctor and obesity patient advocate put it:
"Maybe it's too good to be true." The drug works by targeting the body,
not the mind.
Unlike rival therapies that suppress appetite,
Zafgen's drug, beloranib, is designed to make the body produce less fat and
burn off the excess as fuel. "This is in contrast with other agents that
really only affect hunger, and don't actually restore balance of the fat,"
Zafgen Chief Executive Thomas Hughes told Reuters. Even if all goes well, the
drug is years away from hitting the market. But the company that develops a
potent diet pill without major safety concerns could end up with a "blockbuster" – the industry term for a drug with annual sales of $1 billion.
Obesity in US
More than a
third of Americans are obese, a condition that can lead to heart disease and
diabetes, and a 2012 report by lobby group Trust for America's Health said
obesity cost the US healthcare system up to $210 billion (R2 100 billion) a year. After their
treatments won approval mid-2012, Arena Pharmaceuticals Inc. and Vivus Inc have
been slugging it out to conquer the weight-loss market.
though, have fallen far short of expectations. Some analysts blame marketing
strategies. Others say doctors are yet to be convinced that the safety issues
that led to the withdrawal of earlier diet drugs have been entirely
overcome. "A lot of the obesity drugs historically focus on working signals
in a little area on the hypothalamus," said Kevin Starr, a partner at
Third Rock Ventures, an investor in Zafgen. "That is very close to the
happy signals and sad signals."
and depression are all co-regulated by that same area of hypothalamus,"
said Starr, whose firm specialises in investing in innovative healthcare
companies. These side-effects have resulted in a number of treatments being
withdrawn from the market, including the notorious "fen-phen"
combination, pulled in 1997, and Sanofi's Acomplia, which went off the market
in 2008. Vivus's Qsymia and Arena's Belviq have serious side effects, ranging
from depression and anxiety to heart risks and potential harm to foetuses. And
while both involve signalling the brain, the exact way they work is unknown – a
big concern to those worried about safety.
drugmaker Novo Nordisk's liraglutide, expected to be launched in the US by the
end of 2014, has been associated with higher risks of thyroid cancer and
pancreatitis. In contrast, beloranib appeared safer in a mid-stage trial, with
no serious adverse events reported.
The most common side effects were nausea,
vomiting and sleep disturbance. Beloranib works by blocking an enzyme
known as methionine aminopeptidase 2, or MetAP2, which plays a key role in the
production and use of fatty acids.
Higher fat burn
production of less fat, studies show the drug also leads to a higher rate of
fat burn and improves some key conditions related to heart safety, including
reducing bad cholesterol and lowering inflammatory actions in the
body." Beloranib sounds interesting. Maybe it's too good to be
true," said Jeffry Gerber, a Littleton, Colorado physician who is a member
of patient advocacy group Obesity Action Coalition.
Preliminary data from a
mid-stage study testing beloranib showed the highest dose of the drug caused an
average weight loss of about 22 pounds (10 kg) after 12 weeks of treatment. In
comparison, patients taking the highest dose of Vivus's Qsymia in two separate
late-stage trials lost about 30 pounds and 37 pounds on average after 56 weeks
of treatment. Belviq patients, who completed 52 weeks of treatment, lost an
average of about 17 pounds.
just completed treating patients in the study and expects to report the results
in the next few months. Gerber said for promising drugs in early stages of
development, his main concern is long-term safety – which is the biggest issue
that the US Food and Drug Administration has with Qsymia and Belviq.
were tested and approved to be used along with diet and exercise, while
Zafgen's drug was tested in patients who continued their normal food and
exercise habits. Vivus and Arena declined to comment on Zafgen's drug or the
way it works.
not just about 'x' percent weight loss, it's making a change in the fundamental
underlying metabolic disease, that will probably go on to reduce the cost of
the healthcare system and save lives of these patients," Third Rock's
Starr said. The main challenge for Zafgen is to keep replicating the strong
early results in larger studies, Piper Jaffray analyst Charles Duncan said. He
estimated that it could be mid-2018 to mid-2019 before beloranib gets to
Competing with surgical procedures
wants its drug to compete with weight-loss surgery. "Our aspiration for the
drug is to provide the type of weight loss that one sees in surgical procedures – laproscopic banding, potentially even bypass – although that is a very high
hurdle," CEO Hughes said.
trials, the two FDA-approved lap-bands, made by Allergan Inc. and Johnson &
Johnson unit Ethicon Endo-Surgery Inc., helped patients lose between 40% and 65%
of their excess weight after one year. After three months of treatment,
beloranib led to a 20%-30% reduction in excess body weight, Hughes said.
are about more than halfway to reaching the levels of weight loss seen in
bariatric surgery in 12 weeks," he said. Hughes, 54, joined Zafgen in 2008
after leading the development of Novartis's successful type 2 diabetes drug
vildagliptin, known as Galvus. Zafgen licensed beloranib from South Korean
antibiotic maker Chong Kun Dang Pharmaceutical Corp.
worldwide development and marketing rights to the drug, excluding Korea. Zafgen,
based in Cambridge, Massachusetts, is funded by three venture capital firms –
Third Rock, Atlas Venture and Alta Partners. It has raised about $68 million
since it was founded in 2005.
listing in the next six to 12 months is not out of the question, Hughes said,
adding that Zafgen would also consider investment and takeover offers from
strategic partners. "There has been a bit of an exodus from the obesity
space [by Big Pharma]," Hughes said. "So it shouldn't surprise
anybody to know that we have been a subject of interest as partners."