Pharmaceutical companies developing non-opioid pain medications

The pharmaceutical
industry is looking to bring more non-opioid pain medications
into market.
Shayanne Gal/Business
Insider

• With the opioid crisis in full force and doctors
  feeling pressure to cut back on the number of opioid
  painkillers they prescribe,
  chronic-pain patients aren’t left with many alternatives
  that are as effective or accessible.
• So the pharmaceutical industry is looking to bring more
  non-opioid pain medications into market, with 17 drugs in
  late-stage clinical development and 40 drugs in early-stage
  development.
• One of the new types of drugs is used to block the
  nerve-growth factor, which can reduce pain in patients with
  osteoarthritis, chronic back pain, and cancer pain. The two
  newsworthy drugs in this category are tanezumab and
  fasinumab.
• Centrexion, a capsaicin-derived drug, has also received
  buzz for its pain-reducing properties.

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Debbie Page, 66, has suffered from chronic pain for half of her
life after a back injury left her with the inability to stand for
more than a few minutes at a time.

“After an hour I can’t think or see,” she said. “The pain takes
over and it’s torture.”

Page, a part-time occupational therapist in Boston, said
oxycodone saved her life.

“I was at a point where I was seriously considering suicide or
moving to Mexico. In trying everything, the only thing that ever
has worked is opioids — ever,” she said. “They’re just magic.”

For many patients like Page, opioids are the only way they’re
able to manage chronic pain and lead full lives. Traditional
nonaddictive medicine such as a class of drugs known as
nonaspirin nonsteroidal anti-inflammatory drugs, or NSAIDs, does
not work for everyone.

But with the opioid crisis in full force, doctors are feeling
pressure to cut back on the number of opioid painkillers they
prescribe, even among patients using them responsibly. This means
the more than 100 million Americans suffering from chronic pain
aren’t left with many options that are as effective or
accessible.

Shayanne Gal/Business Insider

For patients looking for alternatives to opioids, it can be hard
to get them paid for by insurance companies. Treatments such as

radio-frequency ablation, which uses radio-frequency waves to
disrupts the ability of nerves to send pain, steroid injections
and
nerve-blockers, which are locally injected temporary
anesthetics, are often labeled as “experimental” and
“investigational” by insurance companies, effectively
making them ineligible for reimbursement, despite being
heavily recommended by many pain specialists.

So even when new technology, such as
neuromodulation shows effectiveness, it can still be
difficult for patients to get access to it. An increasing number
of lawmakers are opening
up to the concept of using marijuana as an opioid
alternative, especially as a new
study published in the Journal of the American Medical
Association found that states with medical marijuana laws had
lower opioid-associated deaths.

At the same time, drug companies and doctors alike are on the
hunt for new ways to tackle the complexities of managing chronic
pain. Some of the new approaches look to lifestyle fixes and
cognitive therapies, while others look toward more
medical-related interventions such as surgery and alternative
medications.

‘No doctor will take me’

There were more than 42,000
deaths in the US attributed to opioids in 2016, and 40% of
all opioid-overdose deaths involved prescription opioids,
according to the Centers for Disease Control and Prevention.

State lawmakers and some health systems, in turn, are putting
measures in place to cap the number of opioid prescriptions that
doctors dole out.

As a result, the number of opioid prescriptions nationally fell
22% between 2013 and 2017, according to a recent study from the
IQVIA Institute for Human Data Science.

Shayanne Gal/Business Insider

Page said she was already feeling the effects.

“I’m concerned every month … no doctor will take me,” she said.
“I’ve had to travel three hours one day to fill my prescription.
Everyone’s out.”

The problem is opioids are hard to beat when it comes to initial
pricing, convenience, and immediate effectiveness.

Margaret Fitzpatrick, 52, was doing acupuncture daily to manage
her chronic pain but had to cut back because the treatment wasn’t
covered by her insurance company after she exceeded 13 visits a
year.

“Not having access to good therapists or acupuncture or massage
is really frustrating especially with the opioid crisis and
doctors not prescribing them when alternatives aren’t covered by
insurance,” she said. Fitzpatrick was a teacher for many years,
but had to stop working two years ago because of her pain.

“For those of us who are disabled, we don’t have a lot of income,
and you’re taking away the alternatives that would work,” she
said.

For the most part, opioids work to reduce pain for a large number
of people with different types of pain conditions, and there are
usually minimal side effects if the patient has no history of
substance-use disorder, said Cindy Steinberg, national director
of policy and advocacy at the US Pain Foundation.

Shayanne Gal/Business Insider

Opioids work by impersonating chemicals in the brain called
endorphins, which act like messengers between nerve cells. The
endorphin molecules bind to corresponding receptors on cells that
exist in both the brain’s pleasure center, and also on nerve
cells that reside within the body’s pain network.

These mock endorphins are far more potent than the natural ones
produced by the body, so as they do their magic, they can elicit
a wash of intense euphoria along with pain relief. But the body
does become tolerant to this, and with every hit it needs more
the next time to achieve the same response. Stopping entirely
makes the body sick from withdrawal.

Samantha Lee/Shayanne Gal/Business
Insider

“Withdrawal is extremely painful,” Page said. “I have to take the
pill. The torture that people have to go through when they’re
suddenly reduced or kicked off is inhumane.”

Finding alternatives

Dr. Janet Pearl, who runs a pain center outside Boston, described
the pain she treats as a spectrum. Some types of anti-seizure
medications and a class of antidepressants are effective at
managing pain, while regenerative medicine is also an exciting
area to tap into. For some patients, the body’s wear and tear and
genetics can make pain worse. For others, cognitive behavioral
therapy works wonders. Patients need to be evaluated on a
case-by-case basis, Pearl said.

Shayanne Gal/Business Insider

Julie Morgenlender, a 39-year-old personal-finance consultant
who’s struggled with chronic pain for 20 years, has tried myriad
treatments, including acupuncture, naturopathic medicine, and
disease-modifying drugs like Plaquenil. She also suffers from
autoimmune thyroid disease, for which she takes a drug called
Nature-Throid.

“I have pain from each of these different things, and each one is
just one piece of the puzzle,” she said.

According to a
Bio Industry Analysis published in February, pain accounts
for a greater amount of direct US healthcare costs compared to
diseases like cancer, diabetes, or cardiovascular dysfunction.
Four times as many Americans suffer from chronic pain than
diabetes.

Yet pain conditions are on the tail end of receiving venture
funding. There are 11 unique types of drugs in the US approved
for pain outside of opioids, easily eclipsed when compared to the

93 unique types of cancer drugs in 2017.

Pharma companies are just starting to invest more in drugs
targeting chronic pain. There are 17 pain drugs in late-stage
development to treat forms of chronic pain, as well as about 40
drugs in earlier human clinical trials.

Shayanne Gal/Business Insider

The types of formulas used to create pain medications needs to be
expanded, and there needs to be wider discussion and increased
legislation to provide access to these medications, said Neel
Mehta, medical director of pain medicine at Weill Cornell.

“This is changing, but there was a time where if you wanted to
use an alternative treatment, you had to establish failure of an
opioids, purely because of cost,” Mehta said.

One of the main approaches researchers are looking into is a
class of drugs that work with nerve growth factor. NGF is
important in developing babies’ nervous systems, and they evolve
to play a huge part in how adults feel pain.

“It stimulates peripheral nerves, and thereby you end up with a
barrage of pain signals from the skin or muscles up through the
body up through spinal cord into the brain where it’s interpreted
as pain,” Ken Verburg, a senior vice president for development at
Pfizer, told Business Insider. He’s leading the development of
tanezumab, one of the NGF inhibitors. Tanezumab blocks the effect
of nerve-growth factor and lessens the sensation of pain.

The Canadian Agency for Drug and Technology in Health in February

listed the approach as one of the emerging non-opioid drugs
for management of chronic noncancer pain. It’s one of the two
major NGF-binding drugs that have surfaced in the pharmaceutical
world.

• Pfizer and Lilly, tanezumab: In July, the drug
  said it had achieved its goal of lowering pain in a late-stage
  trial. It’s used to treat osteoarthritis, chronic low-back
  pain, and cancer pain.
• Regeneron and Teva, fasinumab: A rival drug to
  tanezumab, it also targets low-back pain and osteoarthritis.
  Fasinumab was halted during its phase 2b trial in 2016, and in
  May, the company ditched the higher dosage of the drug. In
  mid-August, the companies announced positive results in a
  late-stage trial.

NGF blockers haven’t always had a storied past. Fulranumab, an
anti-NGF pain drug, was
returned by Johnson & Johnson to Amgen in 2016 after a
late-stage clinical trial because of safety concerns and has
since been
discontinued.

There’s also a group of capsaicin-derived drugs that target the
caspacin receptor (TRPV1) in the body to inactivate local pain
fibers that transmit signals to other neurons. Capsaicin is a
chemical extract from peppers. Repeated exposure to it cause
substance P, a protein that transmits pain signals, to be used
up, which reduces pain.

• Centrexion, CNTX-4975: In a phase 2 study, the
  drug kicked in within a few days and lasted about six months.
  “What our product does is it quiets down just the ends of pain
  fibers like giving a haircut,” Kerrie Brady, chief business
  officer of Centrexion, told Business Insider in January. “And
  that stops the connection and stops the pain signaling going
  forward.”
• Acorda Therapeutics, capsaicin 8% patch: It
  was approved by the FDA in 2009 to manage neuropathic pain. The
  patch is undergoing a late-stage trial with osteoarthritis
  patients.

Of the drugs in development, there are a couple of promising new
candidates like
Angiotensin II signaling that has a role in pathways of
peripheral neuropathic pain, and EMA401, an old antagonist being
repurposed
by Novartis to
treat neuropathic pain from diabetes.

Cornell’s Mehta says that while these new drugs are promising,
more needs to be more done about educating pain patients.

“Patients are open to it, but there are patients out there who
are more apprehensive about it. We need to be cognizant of that.
We need to do a good job of counseling, to be understanding of
patient concerns, and encourage trials of other medications,” he
said. “We also need to understand with the new therapies coming
in who is best suited for that.”

Although Steinberg is waiting until all the clinical trials are
done and the drugs formally enter the market, she holds out hope
for the future of drug innovation in treating pain.

“If a drug can be as effective as opioids without the risk of
addiction for those with substance-use disorder,” she said, “it
is worth the investment.”

Lydia Ramsey contributed reporting.