The mainstay treatments for autoimmune conditions still subject patients to needles, either injections or infusions. ChemoCentryx’s nearly 25-year quest to develop more convenient pill therapies for chronic conditions has finally paid off. On Friday, the FDA approved ChemoCentryx’s lead drug, a pill developed to treat a rare autoimmune disorder.
The regulatory nod means adult patients now have a twice-daily oral treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The decision also makes the drug the first approved product for Mountain View, California-based ChemoCentryx. The company will market the drug under the name “Tavneos.”
Investors welcomed the drug approval news. ChemoCentryx’s stock price was $38.41 at the market close Friday, up nearly 96% from Thursday’s closing price.
Though there are some pill therapies for autoimmune conditions, the top-selling products are biologic therapies made from antibodies and proteins. These large molecules can’t be absorbed by the gut or they don’t hold up well in that environment, so they’re formulated as injections or infusions. ChemoCentryx formed in 1997, a time when a wave of new biologic medicines reached the market, bringing new treatment options for chronic autoimmune conditions and generating blockbuster sales for the companies that made these products.
ANCA-associated vasculitis is a group of autoimmune disorders in which neutrophils, a type of white blood cell, causes inflammation and damage to small blood vessels. The resulting inflammation damages the organs of the body, and commonly affects the kidneys.
There are no biologic medicines available for ANCA-associated vasculitis. Standard treatment includes immunosuppressive drugs and steroids, which bring a wide range of side effects (and also are administered by injection or infusion). Suppressing the immune system makes a patient more susceptible to infections; cancer and metabolic toxicity are among the other potential side effects. According to ChemoCentryx, between 60% and 80% of patients who receive these treatments achieve complete remission of the disease, but relapses or flare ups are common, which restarts the treatment cycle. Those relapses can lead to irreversible organ damage.
ChemoCentryx’s drugs are small molecules formulated into pills. These molecules are designed to block receptors that regulate the trafficking of immune cells. The company says its molecules are selective – they hit their intended targets but leave the rest of the immune system intact. Tavneos is designed to target C4AR, a receptor that plays a key role in how ANCA-associated vasculitis develops.
The ChemoCentryx drug was evaluated in a Phase 3 study that enrolled 330 ANCA-associated vasculitis patients in 20 countries. Those patients were randomly assigned to receive the pill alongside standard of care therapies, or the standard of care alone. The main goal was to measure the number of patients who showed remission at 26 weeks; the second primary goal was to measure sustained remission at 52 weeks.
Clinical trial results showed that 72.3% of patients in the avacopan group achieved the first main goal of showing remission at 26 weeks compared to 70.1% of those who received standard treatment. The separation between the two groups was more pronounced after one year. At week 52, 65.7% in the avacopan group achieved sustained remission compared to 54.9% in the standard of care group. Full study results were published in February in the New England Journal of Medicine.
Excluding the worsening of vasculitis, serious adverse events were reported in 37.3% of patients who received the ChemoCentryx drug. Those reactions included nausea, headache, hypertension, diarrhea, and vomiting. Liver toxicity was reported in nine patients in the avacopan group and six in the standard of care group. Those problems resolved after stopping treatment with the study drug and other medicines that could potentially affect the liver.
Approval of the ChemoCentryx drug was far from certain. In May, an FDA advisory committee vote deadlocked on the question of whether the efficacy data supported approval. The question of whether the therapy’s safety profile supported approval drew a 10 to 8 vote. On the third question, asking whether the drug’s risk-benefit profile supported approval at a twice-daily 30 mg dose, the vote was also 10 to 8 in favor.
After the advisory committee meeting, ChemoCentryx submitted additional information to the FDA to address the panel’s comments. This amendment to the drug application pushed out the target date for a regulatory decision by three months. Approval of Tavneos covers the two main forms of ANCA-associated vasculitis. The addressable U.S. market of adults that can be treated with Tavneos is about 9,500, according to an investor presentation. Tavneos will not eliminate steroid therapy and the side effects that those drugs can bring. The FDA approved the ChemoCentryx drug for use alongside a type of steroid called glucocorticoids. The recommended dose is 30 mg (three 10 mg capsules) taken twice daily with food. ChemoCentryx said it expects Tavneos will launch in coming weeks. The drug’s annual wholesale price, before any discounts or rebates, will be between $150,000 and $200,000.
A company’s path to its first FDA approval is never a straight line, and ChemoCentryx’s path zigged and zagged well before Tavneos. The biotech was previously partnered with GlaxoSmithKline, which had taken an inflammatory bowel disease drug candidate from the company into late-stage testing. In 2013, GSK returned the rights to the drug after it failed a Phase 3 test, ending the multi-drug alliance. But GSK still claims a small piece of avacopan’s success now that it is approved . The compound was covered under the original alliance. According to that agreement, if GSK does not exercise its option on a ChemoCentryx drug that demonstrates proof of concept in a clinical trial, the rights stay with ChemoCentryx but GSK is owed a 3% royalty on annual global sales. The total royalty is capped at $50 million.
ChemoCentryx is developing avacopan for two other rare autoimmune conditions; it’s in Phase 2 testing for C3 glomerulopathy and hidradenitis suppurativa. The ChemoCentryx pipeline also includes drug candidates for other inflammatory and autoimmune conditions, cancer, and chronic and rare kidney diseases.
Image from ChemoCentryx investor presentation
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