FDA Approves Antitoxin Antibody

Nature Reviews Drug Discovery | Published online 29 Nov 2016 NEWS & ANALYSIS

NEWS IN BRIEF

European Union. Results can be accessed FDA approves antitoxin antibody at https://clinicaldata.ema.europa.eu/web/ The FDA has approved Merck & Co’s bezlotoxumab to reduce the recurrence of Clostridium cdp/home. difficile infection, marking the first approval for a new approach to the treatment of bacterial As Nature Reviews Drug Discovery went infections. Unlike antibiotics, which kill pathogenic bacteria, bezlotoxumab is an antibody that to press, the agency had released data for mops up toxins that are released by C. difficile. only two drugs: Onyx Pharmaceuticals’ Although antibiotics can control C. difficile, the infection recurs within weeks in around carfilzomib and AstraZeneca’s lesinurad. 25% of patients. In two phase III trials that tested bezlotoxumab in conjunction with The combined reports for these two drugs standard of care antibiotics, Merck showed that their adjunct antibody reduced recurrence alone are 260,000 pages long. The European to 16–17% of patients. The most common adverse reactions included nausea, pyrexia and Medicines Agency (EMA) plans to publish headache. clinical data on 2−4 products per month. Analysts expect the market for bezlotoxumab to be modest, at US$212 million per year in Once it has cleared a backlog of publishable worldwide sales by 2020. However, the approval could boost interest in the growing pipeline reports, it will release data for new drugs of antibodies for the treatment of bacterial infections (Nat. Rev. Drug Discov. 14, 737–738; within 60 days of approval decisions. 2015). It will also release data for drugs that are In some cases these antibodies, like bezlotoxumab, act on bacterial toxins. AstraZeneca’s withdrawn before a decision is made. phase II candidate MEDI4893 targets the Staphylococcus aureus alpha toxin, for example, “Patients and clinicians have been and Bellus Health’s phase II shigamab targets the Escherichia coli shiga toxin type 2. Other waiting a long time for clinical trial data,” antibodies target the bacteria more directly. AstraZeneca’s phase II candidate MEDI3902, for said Yann Le Cam, Chief Executive Officer example, targets the exopolysaccharide PsI and the secretion protein PcrV on the body of of EURORDIS – Rare Diseases Europe and Pseudomonas aeruginosa bacteria. member of the EMA’s management board. One benefit of these targeted antibodies is that they might be less likely to induce broad “Access to this new knowledge base can resistance among bacteria or disturb the healthy microbiome. help to accelerate innovation by reducing Asher Mullard duplication of research and de-risking some new developments.” Asher Mullard forward, Pfizer discontinued development PCSK9 pipeline of its would-have-been competitor bococizumab. The antibody had been in Access to medicines report cards Promising phase II data from The Medicines phase III trials in more than 27,000 patients. Company’s inclisiran have paved the Safety data showed, however, that it was more Drug companies are getting moderately better way for phase III trials of a long-acting immunogenic than the competition. Pfizer at enabling access to drugs for people in low- oligonucleotide-based PCSK9 inhibitor. also cited “the evolving treatment and market and middle-income countries shows a recent Although the FDA has already approved two landscape”, referencing disappointing sales report from the non-profit Access to Medicine PCSK9 blockers — Amgen’s evolocumab and for the approved PCSK9 inhibitors. Foundation. Sanofi and Regeneron’s alirocumab — these Payers are pushing back against the high GlaxoSmithKline topped the biennial subcutaneously delivered lipid-lowering cost of these drugs — around US$14,000 per ranking, for the 5th consecutive time, antibodies are administered every 2–4 weeks patient per year — because of the absence as followed by Johnson & Johnson and Novartis. for the treatment of hyperlipidaemia. If data yet of definitive data proving that they reduce Companies are also doing a better job hold up, inclisiran might only require two or cardiovascular events. of addressing global health priorities, says three injections per year. The field is awaiting the results of large the report. The top 20 pharmaceutical The Medicines Company presented the cardiovascular outcomes studies that could companies are developing 420 products for new data at the American Heart Association open up the market. Another study that was the most burdensome diseases of low- and (AHA) Scientific Sessions 2016 in New Orleans presented at that AHA meeting provided middle-income countries, up by more in November. Preliminary data from the first some encouragement. Researchers dosed than 100 products since the 2014 Index. 189 patients in a phase II study of the RNA 968 patients with evolocumab or statins, “We see evidence that collaborative interference (RNAi)-based drug showed that and used ultrasound to measure the size of R&D models are engaging the industry in one injection reduced low-density lipoprotein atherosclerotic plaques, a risk factor for heart developing urgently needed medicines cholesterol (LDL-C) levels by 59% compared attacks. Plaques shrank in 64% of evolocumab they would not otherwise be considering with placebo at day 60, and that two injections patients, and in 47% of statin-treated patients. because there is not enough of a commercial reduced LDL-C by 57% at day 120. Treatment Asher Mullard market for them,” said Jayasree Iyer, was well tolerated. There was one death and Executive Director of the Access to Medicine one case of increased liver enzyme levels, Foundation. but investigators said neither were related to EMA opens its data vaults The report also found that good practice treatment. is limited to a narrow range of products But even as The Medicines Company European regulators have started and countries, providing plenty of room for prepared to move its proprotein convertase publishing the full clinical trial reports improvement. subtilisin/kexin type 9 (PCSK9) programme for drugs that are approved for use in the Asher Mullard