Wire: Bloomberg News (BN) Date: Jun 28 2017 6:01:01
Life After Opioids: Drugmakers Scramble to Concoct Alternatives
By Caroline Chen
(Bloomberg) -- In the wake of mounting overdoses and deaths
from the opioid-addiction crisis sweeping across the U.S.,
drugmakers are racing to come up with safer painkillers.
Companies are highly motivated to create alternatives to
the $4 billion opioid market. The federal government is cracking
down on lax prescriptions that contribute to many thousands of
deaths a year and has started to block the sale of medications
it considers unsafe.
Drugs such as morphine, fentanyl, and oxycodone are such
powerful analgesics because they so effectively block pain
signals by acting directly on the brain. Since they work at such
a fundamental level, these medications would be perfect
painkillers were it not for their tendency to cause addiction.
“In medical school, we used to play this game: If you could
only take five drugs to a desert island, what would they be?
Everyone would say morphine because it’s such a terrific drug
for pain,” said Morgan Sheng, vice president of neuroscience and
molecular biology at Roche Holding AG’s Genentech unit.
Drugmakers are tackling the challenge from all angles,
working to create an arsenal of medications tailor-made for
different forms of pain. These new drugs are drawing from the
known pain-modifying attributes of chili peppers and cannabis,
as well as human genetic mutations that alter how people
experience pain to concoct new treatments for the nation’s 100
million chronic sufferers. One of the more far-out medications
in development is derived from a deadly toxin found in cone
snails.
Many of these new innovations are intended to treat
osteoarthritis pain, a huge market as the baby-boomer generation
ages. Centrexion Therapeutics Corp. is developing an injection
using synthetic capsaicin, the active ingredient in chili
peppers. A mid-stage trial showed a single injection in
patients’ knees brought significant relief for as long as six
months.
Read more: How the opioid crisis unfolded -- a QuickTake
Explainer
Capsaicin reduces the hyper-sensitive nerve endings in the
knee, "like a hair cut," said Centrexion Chief Medical Officer
Randall Stevens. The nerves will eventually grow back, requiring
repeated treatment. The drug has the added benefit of not
affecting nerves that sense touch and pressure, so the joint
will retain some normal sensation, minus the most active pain
sensors, said Chief Executive Officer Jeffrey Kindler.
Other new arthritis meds are nerve-growth-factor
inhibitors, which block pain signals in nerve cells beyond the
brain, such as in skin and muscle. This drug class was dogged by
concerns that it worked so well, patients overused the affected
joint. That led the U.S. Food and Drug Administration to issue
temporary suspensions of some early trials. Pfizer Inc. and Eli
Lilly & Co., which co-developed one of these drugs, have
adjusted doses and now have the leading treatment, called
tanezumab, which received fast-track review from the FDA on June
13.
Taking another tack, Genentech is developing an oral drug
based on extremely rare genetic mutations that prevent people
from feeling pain. Studying them helped scientists discover a
pathway in the body called the Nav 1.7 sodium ion channel that’s
implicated in pain. By modulating the pathway, Genentech hopes
its pill can tamp down suffering.
Cannabinoid Receptors
It’s still early days. The drug, called GDC-0310, just
completed a Phase 1 safety trial. Genentech’s Sheng said he’s
hopeful it will have few serious side effects since humans with
the mutated gene are otherwise normal, save for a loss of the
sense of smell. Sheng said it should be effective against
musculoskeletal pain, such as in the lower back. Amgen Inc. is
also in the early stages of developing a Nav 1.7 blocking drug.
Other pre-clinical treatments include Cara Therapeutics
Inc. and Centrexion experimental drugs that target the
cannabinoid receptors, mimicking the analgesic effect of
marijuana. Meanwhile, scientists at Hunter College in New York
are working to make an intravenous painkiller based on a toxin
found in cone snails.
Opioids probably won’t ever be shelved for good -- they’re
just too potent. So a handful of companies are working on
versions that are safer and less addictive. Nektar Therapeutics
has created an opioid that’s designed to cross the blood-brain
barrier very slowly, which results in a lowered euphoric effect.
Because of its slower entry into the brain, however, the drug
won’t be able to help with cases of acute pain. Nektar is
developing it for patients with chronic lower backaches.
Trevena Inc., meanwhile, is working on a safer opioid for
hospital use that doesn’t slow patients’ breathing like many
current opioids do. Said CEO Maxine Gowen: "We’re all longing
for the day when a non-addictive pain therapy with no side
effects comes along, but until we find that perfect drug,
opioids will continue to have a place."
