Aiming for muscle-spasm relief without sedation in a purified drug
Neurana Pharmaceuticals is focused on developing a single new product, a purified form of the drug tolperisone as an oral, non-sedating new treatment for muscle spasms. A previous form of tolperisone had been sold widely in Europe, Asia, and Latin America, but was never approved by the U.S. FDA because of an impurity it contained. With a full sweep of clinical development now underway, the purified tolperisone product will follow the 505(b)(1) process, the “traditional” NDA route seeking first market approval. It has completed Phase 1 and 2 studies and is slated to begin a Phase 3 study later this year.
WHAT’S AT STAKE
The origin of little-known Neurana traces back to well-known industry figure David Hale. (See “How The Journey To Entrepreneurial Biotech Begins,” August 2015.) Hale secured what would become the startup’s lead muscle-spasm compound, tolperisone, and brought its management team together. Hale had formed a relationship with the Austrian company Sanochemia Pharmazeutika AG, which developed a form of tolperisone without the impurity that had kept the original drug unavailable in the United States. The purification allowed the company to win U.S. composition-of-matter and process patents for the new form of tolperisone as well. It is not just developing a new delivery form, but effectively a new compound and a new treatment option.
The stakes for the company have since moved to the next big step: clinical development. Neurana needed to prove the product had superior advantages over the long-dominant muscle relaxant on the market, Flexeril (cyclobenzaprine). Thus, after fresh tox studies, the product went into a proof-of-concept Phase 1 trial that tested patients in a driving simulation, where subjects’ performance on tolperisone compared quite favorably to those on cyclobenzaprine. Supporting its “non-sedative” effects, tolperisone produced none of the acute and lingering drowsiness so familiar to users of cyclobenzaprine. The three-armed study of 30 healthy volunteers randomly rotated every subject through placebo, tolperisone, and cyclobenzaprine over three weeks to highlight the comparison.
“What we saw was dramatic compared to cyclobenzaprine,” says Craig Thompson, Neurana’s president and CEO. “On the first day, after patients had taken two doses, tolperisone looked identical to placebo, and with cyclobenzaprine we saw a dramatic increase in impairment, so much so that, on this task, it was above being legally impaired in most states, with a blood alcohol content of 0.05%.”
Neurana has since completed a positive Phase 2 dose-ranging study of tolperisone for acute back pain and stiffness caused by painful muscle spasms. In addition to indicating significant overall efficacy, the trial showed no safety concerns or sedative effects versus placebo. Muscle spasm is a large potential market, and according to Thompson, recruitment of subjects for the Phase 2 trial reflected pent-up demand for a new treatment option in the muscle-spasm space. “We enrolled the Phase 2 study of 415 patients in four and a half months, which we believe is a surrogate for the demand and willingness in physicians looking for alternatives. We enrolled around 38 patients a week, which is remarkable,” he says. As the company prepares for its Phase 3 study of tolperisone in muscle-spasm back pain, it continues to conduct additional Phase 1 studies as needed for its eventual NDA submission.
Thompson, who learned the ropes in his former career at Pfizer and Merck, advises: “You always need to do the required steps correctly and make sure that you cover all the bases so you do your scale-up experiments at the right scale, and we’re doing all those experiments properly.” Even for the most exotic of new biotherapeutics, far removed from the small-molecule world, such journeyman advice is solid. Innovation means stepping up to a new standard. If you want to show your way is better, carefully take all the required steps to prove it.
Employees: 10 Headquarters: San Diego, CA
$65M Total raised
Investors: $60M Series A, May 2018, led by Sofinnova Other Investors: HIG BioHealth Partners, Longitude, New Leaf Venture Partners, MagnaSci, Hale BioPharma Ventures
Partners: Sanochemia Pharmazeutika AG granted Neurana exclusive rights to develop and commercialize tolperisone in North America
Latest Updates September 2019: Positive Phase 2 data demonstrating tolperisone efficacy without increasing sleepiness in treating acute back pain due to muscle spasmn