All four doses of fasinumab, a nerve growth factor (NGF) therapy under development at Regeneron Pharmaceuticals Inc., helped 338 patients with moderate-to-severe osteoarthritis pain in their hip or knee achieve statistically significant relief at week 16 of a phase II/III study.

The study tested subcutaneous delivery of the drug in patients with significant baseline pain who were either intolerant of or inadequately served by acetaminophen and at least one oral nonsteroidal anti-inflammatory drug (NSAID) and an opioid. Patients were dosed every four weeks through week 12 and are being studied for an additional 20 weeks off treatment.

Regeneron had previously evaluated an intravenous formulation of fasinumab in osteoarthritis patients. This is its first trial of a monthly subcutaneous regimen.

On the study's primary endpoint, fasinumab-treated patients reported less pain at 16 weeks when compared to placebo on the 10-point Western Ontario and McMaster Universities Arthritis Index subscale for pain. Depending on the dose, fasinumab helped those treated reduce their baseline pain scores by an average 3.03 to 3.65 points vs. a 2.25 point reduction delivered by a placebo.

But in spite of the drug's benefits, more participants treated with fasinumab also reported neuro-musculoskeletal adverse events (17 percent) than those given a placebo (6 percent). Also, four cases of rapidly progressive osteoarthritis were recorded, one in each of the 3 mg, 6 mg and 9 mg fasinumab dose groups.

Taken together with earlier concerns over the NGF class that led to FDA clinical holds on several trials in the space, including a study of fasinumab in 2001, analysts were wary about the drug's prospects, saying that they're holding out for long-term safety data.

Suntrust Robinson Humphrey senior biotechnology analyst Yatin Suneja said that his team is looking for 36-week data from the phase II/III study as well as data from an ongoing long-term phase III study in which Regeneron is slated to enroll up to 10,000 participants.

Leerink Partners analyst Geoffrey Porges pointed out that, "with the potential efficacy of the drug less in question," adverse events were more likely to "be a major focus moving forward as the patients are followed for an additional 20 weeks and the complete results of the study are subsequently released." Leerink forecasts fasinumab could be a modest contributor to Regeneron's top line, assuming it contributes about $100 million in revenue with a 2018 launch, with sales increasing to about $400 million in 2020 following an ex-U.S. launch in 2019, accounting for about 4 percent of the company's projected 2020 revenue.

Whether concerns of a similar nature moved Sanofi SA, Regeneron's one-time partner on the drug — and still its partner on many other projects — to elect not to continue co-development of fasinumab, which it did in 2012, were not clear.

But concern over the safety of anti-NGF drugs at the FDA is certainly nothing new. It took particular prominence in mid-2010, when the agency placed a partial clinical hold on Pfizer Inc.'s tanezumab following reports of adverse events in osteoarthritis trials. Despite phase III data showing that all three doses of tanezumab tested led to significant improvements on pain and function tests, Pfizer suspended the program, which had arrived in its portfolio by way of its acquisition of Rinat Neuroscience Corp. (See BioWorld Today, June 25, 2010.)

Studies of tanezumab have since resumed. According to Thomson Reuters Cortellis Clinical Trials Intelligence, in March, a double-blind, randomized, placebo-controlled, phase III trial to evaluate the safety and efficacy of tanezumab in as many as 810 patients with osteoarthritis of the hips or knee was planned in Spain. The trial is expected to complete in May 2018.

Another recombinant IgG2 anti-NGF candidate, fulranumab, has not had such a durable rebound. Following an FDA clinical hold placed on its development in osteoarthritis and cancer pain in December 2010, the drug failed to fully recover once the holds were lifted, even though Johnson & Johnson's subsidiary Janssen Pharmaceuticals took up its cause. With a license from Amgen Inc., it started a phase III trial for osteoarthritis pain in April 2015. Last month though, Janssen discontinued the phase III program. It said that the decision was based on strategic portfolio prioritization and was not based on any emerging safety concerns from phase III studies of the drug.

Shares of Regeneron (NASDAQ:REGN) gained $7.81, to close at $384.52 on Monday.