2020年8月25日

2020年8月25日,倫敦——五年後Amgen inc .)以3億美元的價格,出售荷蘭VC Forbion重新Dezima製藥BV和其唯一產品obicetrapib,病人不能容忍他汀類藥物的降膽固醇藥物。IIb階段產品現在Newamsterdam製藥BV的基礎,創業Forbion和共同創始人注入了€2000萬(合2370萬美元)的種子資金。新公司正在與FDA和EMA第三階段發展計劃,並將提高“實質性”輪在今年年底之前。雖然做了一些工作的合成和製造obicetrapib,安進沒有進展在臨床開發獲取每日一次口服膽固醇酯轉移蛋白(CETP)抑製劑在2015年9月和2017年10月削減它。結果,沒有一個裏程碑付款被觸發,桑德Slootweg說管理合夥人Forbion Newamsterdam和椅子。安進公司並不是唯一放棄CETP程序。事實上,位於加州千橡市,公司決定歸咎於心血管結果數據從競爭對手的產品。但Slootweg說Forbion和共同投資者在obicetrapib Dezima始終堅定的信徒。“當我們把它賣給了安進公司,這是一個典型的結構化協議,以3億美元和12.5億美元的裏程碑。我們仍在等待的平衡,所以當安進公司決定不繼續發展我們決定我們應該試著捕捉的價值和得到一個偉大的藥物的病人,”Slootweg告訴BioWorld。 CETP is involved in cholesterol transport. It is responsible for catalyzing the transfer of cholesterol molecules from high-density lipoprotein particles to low-density lipoprotein particles, which eventually contribute to atherosclerosis and to the formation of other lipoproteins. Slootweg said obicetrapib has the potential to address the market of approximately 32 million people globally whose cholesterol levels are not well-controlled by statins, or who are statin intolerant. “We believe that obicetrapib has megabuster sales potential,” he said. In the phase IIb 364-patient trial conducted by Dezima, obicetrapib reduced the number of apolipoprotein B-containing particles that constitute LDL-c, with an average lowering of 45 percent at a 5-mg daily dose. The drug was well-tolerated. The main torch bearer for obicetrapib is John Kastelein, CSO of Dezima and now of Newamsterdam, who is chair of the department of vascular medicine at the Academic Medical Center at the University of Amsterdam. He rescued the drug from the parking lot at Mitsubishi Tanabe Pharma Corp., co-founding Dezima in 2013. “In my opinion, obicetrapib is a best-in-class CETP inhibitor,” Kastelein said. “We have devised a comprehensive clinical development plan, including a cardiovascular outcomes trial to show all the favorable attributes.” Amgen’s decision to stop development of obicetrapib came two months after Merck & Co. Inc. reported statistically significant results for its CETP inhibitor anacetrapib at the European Society of Cardiology. Although positive, the effect was rather so-so, showing only a 9% relative risk reduction in an outcomes study involving more than 30,000 patients. Other casualties in the field include Eli Lilly and Co.’s evacetrapib and Pfizer Inc.’s torcetrapib. “We’ve taken all the learnings from these other trials and incorporated them into our plans,” Slootweg said. “We don’t intend to make the same mistakes.” For Newamsterdam, the key lesson from other phase III trials is not to combine CETP inhibitors with high-dose statins, because they interact. Kastelein said this makes obicetrapib an ideal drug for patients who are completely statin intolerant or are on a maximally tolerated but less-than-effective dose. In the phase IIb trial, obicetrapib reduced LDL-c by up to 69% when combined with a statin; taken alone there were reductions of up to 45%. The outcomes trial Naarden, Netherlands-based Newamsterdam is planning to show if that leads to clinically meaningful reductions in cardiovascular events. Even at the top the range, in combination with statins, obicetrapib is unlikely to be as effective in reducing LDL-c as antibody-based PCSK9 inhibitors like Amgen’s Repatha (evolocumab) and Sanofi SA/Regeneron Pharmaceuticals Inc.’s Praluent (alirocumab). In addition to the lower costs and advantages of oral availability, Slootweg said the positioning of obicetrapib will be different. “PCSK9 [inhibitors] focus on people who have already had a heart attack. We will treat patients at risk, who have not had heart disease,” he said. The financial terms of the acquisition of obicetrapib were not disclosed. However, Slootweg said Newamsterdam has secured rights to the synthesis and manufacturing improvements Amgen had made to the molecule. Mitsubishi Tanabe retains an interest in the product.