Celgene新药apremilast临床三期研究失败

著名生物制药公司Celgene公司最近宣布公司开发的用于治疗强直性脊椎炎疾病药物apremilast临床三期研究未能发现与对照组有明显差异，因而宣告失败，研究人员最初希望apremilast能够将患者病情改善20%左右。强直性脊椎炎患者的脊柱连接处会出现膨大僵硬现象，并会导致活动受阻等问题，患者发病时间一般超过15年。目前市面上尚没有一种有效、安全的口服药物疗法治疗这种疾病。Apremilast能够阻断人体磷酸二酯酶4的表达，并进而抑制脊柱关节处的膨大。Celgene的研究人员计划下一步将治疗周期由现在的16周延长至52周以观察药物疗效。受此消息影响，公司股价小幅下挫。

详细英文报道：

Celgene's ($CELG) apremilast couldn't quite beat placebo in a late-stage trial on a form of arthritis, imperiling a potential indication for a drug the company believes can break the blockbuster barrier.

In a 490-patient Phase III study, apremilast failed to chart a statistically significant improvement in symptoms of ankylosing spondylitis at 16 weeks. The disease, marked by swelling and stiffening of discs and joints in the spine, can lead to hampered movement and fused vertebrae, and the study's missed primary endpoint was a 20% reduction in severity on a scale set by spondyloarthritis experts.

The study didn't spotlight any new safety concerns for apremilast, and Celgene said its independent data monitoring committee recommended the trial keep moving as planned, noting vaguely that "meaningful efficacy was observed at week 24 in a large subset of patients with early-stage disease." Taking a positive spin on the slip, Celgene said it plans to hold out for 52-week MRI data from the study and eventually launch another Phase III trial on ankylosing spondylitis, possibly zeroing in on that aforementioned subgroup.

"Ankylosing spondylitis is a chronic, debilitating disease, and despite advances over the last 15 years, there remains significant unmet need for a safe, effective, oral therapy--especially for patients early in the progression of their disease," Celgene inflammation and immunology head Scott Smith said in a statement.

Apremilast's late-stage failure sent the Big Biotech's shares down about 3% in premarket trading on Wednesday, and the news has at least partially damaged Celgene's case for the oral treatment as a top seller. Ankylosing spondylitis affects about one in every 200 U.S. adults, according to the Spondylitis Association of America, and losing out on that patient population would mar apremilast's potential.

But Bernstein analyst Geoff Porges said a win in spinal arthritis has always been a bit of a long shot for apremilast, writing in an investor note that, despite the positive subpopulation activity, "we would not hold our breath for a meaningful revenue contribution from this indication."

The drug, marketed as Otezla, won FDA approval in March to treat psoriatic arthritis, but its major catalyst won't come until September, when the agency is expected to make a final call on its potential in psoriasis. If all goes according to plan, Celgene figures apremilast will peak at around $2 billion by 2017. Analysts have tended toward polarity with their sales estimates, and EvaluatePharma pegs the consensus at somewhere around $1.2 billion.

The drug is a small-molecule therapy that blocks the enzyme phosphodiesterase 4 to reduce swelling in joints. Beyond ankylosing spondylitis, psoriatic arthritis and psoriasis, Celgene is developing the treatment for rheumatoid arthritis, the rare Beh?et's disease, atopic dermatitis and inflammatory bowel diseases.