Positive Results for New Osteoarthritis Drug

By Pat Anson, Editor

Two pharmaceutical companies have announced positive results from a Phase 3 study of an experimental non-opioid pain reliever that has a history of safety concerns.

Teva and Regeneron are jointly developing fasinumab as a treatment for chronic pain from osteoarthritis of the knee and hip. The companies say patients treated for 16 weeks with fasinumab injections had significantly less pain and improved function compared to a placebo.

"We are encouraged by these data and look forward to advancing our pivotal Phase 3 fasinumab program in patients with osteoarthritis of the knee or hip, who currently have very limited therapeutic choices to treat their chronic pain, other than with non-steriodal anti-inflammatory drugs or opioids," said George Yancopoulos, MD, President and Chief Scientific Officer of Regeneron.

Fasinumab is a humanized antibody that targets nerve growth factor (NGF), a protein that increases in the body because of injury, inflammation or chronic pain. Fasinumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

Teva and Regeneron say fasinumab was “generally well tolerated” in the Phase 3 study, with similar adverse events (AEs) as in previous trials. Treatment was discontinued due to AEs in 6 percent of the fasinumab patients, about the same as the placebo group. The companies plan to present further details at an upcoming medical conference.

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Regeneron recently halted high-dose trials of fasinumab because the risk of harm outweighed the benefits of the drug. There is some concern that NGF antibodies work too well and encourage osteoarthritis patients to become more active, which accelerates joint deterioration. No cases of joint damage were observed in the current study.

Regeneron and Teva are currently enrolling osteoarthritis patients in three additional Phase 3 clinical trials, including one assessing the long-term safety of fasinumab and two trials comparing fasinumab to standard pain therapies.

There is intense competition about drug companies to develop non-opioid pain relievers that don’t have the risk of addiction and overdose. Pfizer and Eli Lilly are jointly developing a similar NGF inhibitor called tanezumab, which was given fast track designation by the FDA in 2017 to speed its development.

Like fasinumab, there are safety concerns about tanezumab. The FDA ordered a partial halt to clinical studies of tanezumab in 2010 after Pfizer said a small number of osteoarthritis patients taking the drug needed joint replacements. Another safety issue arose in 2012 because the drug caused “adverse changes in the sympathetic nervous system of mature animals.”  Most clinical studies of tanezumab did not resume until 2015.

New Treatments Offer Hope to Migraine Sufferers

By Pat Anson, Editor

Findings from several new clinical studies could pave the way for new treatments that could someday prevent and lessen the severity of migraines.

Migraine is thought to affect a billion people worldwide and about 36 million adults in the United States, according to the American Migraine Foundation. Although there are many treatment options available, most migraine sufferers are not fully satisfied with their effectiveness.

Teva Pharmaceuticals (NYSE: TEVA) is developing a new injectable drug – called TEV-48125 – that is designed to be injected monthly in chronic migraine sufferers who have headaches at least 15 days per month.

"Chronic migraine affects about 1 percent of all adults, yet less than 5 percent of those people receive a correct diagnosis and appropriate treatment," said study author Marcelo Bigal, MD, of Teva Pharmaceuticals. "Most people who receive preventive medication for chronic migraine stop using them, and one reason for that is the drugs can take a long time to become effective.”

In findings published online in the journal Neurology, Bigal reported that TEV-48125 was effective in reducing the length of headaches three to seven days after the first injection. The drug contains an antibody that blocks the calcitonin gene-related peptide that plays a role in migraine pain.

Teva’s Phase II study involved 261 people with chronic migraine who were divided into three groups; one group received a monthly shot for three months with a low dose of TEV-48125, the second group received a high dose and the third group received a placebo shot. Participants then used an electronic diary to record the number and length of their headaches.

After one week, the average number of headache hours went down by 2.9 hours for people taking the placebo, 9.1 hours for people taking the low dose of TEV-48125 and 11.4 hours for those taking the high dose.

After two weeks, the number of days with moderate or severe headaches, fell by 0.8 days for patients getting the placebo, 1.3 days for the low dose and 1.5 days for the high dose of TEV-48125.

“If these results can be confirmed with larger studies, this could be exciting for people with migraine," said Bigal.

Amgen Injectable Migraine Drug

Amgen (NASDAQ: AMGN) and Novaratis (NYSE: NVS) are also developing a monthly injectable drug --- called erenumab – which contains an antibody that blocks a peptide receptor that is believed to transmit migraine pain signals.

In a Phase II study, 667 chronic migraine patients were injected with a placebo or two different doses (70 mg or 140 mg) of erenumab. At the start of the study, patients were experiencing about 18 migraine days per month.

Patients who received erenumab at either dose experienced an average 6.6-day reduction in migraine days, compared to a 4.2-day reduction in those who receive a placebo. Less than five percent of the  patients treated with erenumab had a side effect, such as injection site pain, upper respiratory tract infection and nausea.

Erenumab is currently under evaluation in several large global, randomized, double-blind, placebo-controlled trials to assess its safety and efficacy in migraine prevention. Amgen expects results from a Phase III study of erenumab in the second half of 2016. Depending on the findings, that could result in an early new drug application to the Food and Drug Administration.  

Clinical studies presented this week at the annual meeting of the American Headache Society also highlighted some promising new migraine treatments.

Alder BioPharmaceuticals presented data showing that a single injection of a drug called ALD403 reduces migraine for up to six months. In a recent Phase II study of patients with chronic migraine, ALD403 significantly reduced migraines by 75 percent in up to a third of patients. 

“A 75 percent reduction in migraine days for these patients means a reduction of 12 or more migraine days each month,” said Jeffrey T.L. Smith, MD, Senior Vice President at Alder. “This equates to giving patients back roughly two weeks of their lives after a single administration.”

Researchers at Montefiore Medical Center and Albert Einstein College of Medicine reported results from a placebo controlled study on the efficacy of ubrogepant in treating a single migraine attack. Patients who received ubrogepant reported a reduction in headache severity from severe or moderate to mild or none within two hours.

Ubrogepant is free of known cardiovascular risk and may provide an important treatment option for patients who suffer from cardiovascular disease. 

Migraine affect three times as many women as men. In addition to headache pain and nausea, migraine can also cause vomiting, blurriness or visual disturbances, and sensitivity to light and sound. About half of people living with migraine are undiagnosed.