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CONCLUSIONS

In patients with MDR HIV-1 infection who had advanced disease and limited treatment options, ibalizumab had significant antiviral activity during a 25-week study. Evidence of the emergence of diminished ibalizumab susceptibility was observed in vitro in patients who had virologic failure. (Funded by the Orphan Products Clinical Trials Grants Program of the Food and Drug Adµ²½×

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The FDA has recommended a streamlined trial design for assessing drugs¡¦ safety and efficacy in patients with multidrug-resistant HIV infection, and ibalizumab has recently undergone such a trial. But clinicians and patients should recognize this design¡¦s limitations.

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voiconsulting.com/blogs/news/new-study-on-time-to-peak-sales-for-us-pharmaceuticals

New Study on Time-to-Peak Sales for US Pharmaceuticals

Drug launch curves in the modern era, a new article in the January 2017 issue of Nature Reviews: Drug Discovery, contains projections of relevance for forecasting pharmaceutical sales in the US market. Relying on unit sales for 61 innovative drugs receiving FDA approval between 2000 and 2002, the authors determined that the median product follows an S-shaped launch-to-peak penetration curve: achieving 11% of peak sales in Year 1, 31% in Year 2, 58% in Year 3, 76% in Year 4, 89% in Year 5, and 100% (i.e. peak sales) in Year 6. On an interquartile basis, time-to-peak (TTP) ranged from 4 to 9 years; the minimum TTP was 2 years and the maximum was 14.

Using data from the Supplemental Materials file we find that the average for TTP for first-in-class drugs is 5.65 years as opposed to 6.93 years for subsequent entrants. Unlike other research on the subject, however, the authors did not that there was a statistically significant relationship between entry order and TTP. But, as they note, TTP is distinct from factors such as market share and revenue potential that may be more indicative of first-mover advantage.

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Emerging Therapies in Patients With Virologic Resistance

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MAY 18, 2018

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www.mdmag.com/peer-exchange/hiv-treatment-landscape/emerging-therapies-in-patients-with-virologic-resistance

MD Magazine offers the latest and most insightful coverage of clinical news, medical meetings, and much more!

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MD Âø»x´£¨Ñ³Ì·s¡A¥H¤ÎÁ{§É·s»D¡BÂåÃÄ·|ij¡A¥H¤Î§ó¦hÂåÃĬÛÃö³Ì²`¤J¸ÔºÉ³ø¾É¡C

Joseph Eron, MD: Dan(Daniel), what about new drugs for people who actually might have resistant virus? It¡¦s uncommon, but it can still happen.

Dan (Daniel), ¹ï©ó¨º¨ÇÅ餺¦³¥i¯à¦³§ÜÃĩʯf¬rªº¤H­Ì³Ì·sªºÃĪ«¬°¦ó©O¡H §Úª¾¹D³o¼Ëªº±¡§Î¤£±`¨£¡A¦ý¬O¤´Â¦³¥i¯àµo¥Í¡C

Daniel Kuritzkes, MD: It¡¦s important to acknowledge this, even though the vast majority of patients do incredibly well with the drugs that we usually use. There is still a small number of patients who have extensively resistant HIV. In these patients, coming up with a fully suppressive regimen can be a challenge. Fortunately, there are 2 new drugs that are in development. Both of them are entry inhibitors. One of them is an antibody that has to be given by injection. That is ibalizumab. That¡¦s a drug that, oddly enough, binds to CD4. It doesn¡¦t stop the virus from binding to CD4, but it stops the virus from getting in afterwards. In the laboratory, it doesn¡¦t seem to mess up the function of CD4 cells. There have been clinical trials that show that the drug has a significant effect on virus loads. So, it¡¦s highly active and very well tolerated. When combined with other active drugs, it can improve the chances for virologic suppression in patients with highly resistant virus.

Daniel Kuritzkes, MD: §Y«Kµ´¤j¦h¼Æªº¯f±w¹ï©ó§Ú­Ì¸g±`¨Ï¥ÎªºÃĪ«ªvÀø¤ÏÀ³·¥¦n¡A ¦ý¬O§Ú­Ì¥²¶·­n©Ó»{³o¬O¤@­Ó¨Æ¹ê¡C ²{¦b¤´µM¦³¤@¤p³¡¤À¯f±w¹ï©ó¤HÃþ§K¬Ì¤£¥þ¯f¬r¡]HIV¡^²£¥Í¼sªx§ÜÃÄ©Ê¡C ¹ï©ó³o¤@¤p³¡¤Àªº¯f±w¦Ó¨¥¡A§ä¥X¤@ºØ¥i¥H§¹¥þÀ£¨î¦í¯f¬rªºÃĪ«ªvÀø­pµe·|¬O¤@¤j¬D¾Ô¡C ©¯¹Bªº¬O¡A²{¦b¦³¨âºØÃĪ«³£¦bµo®i·í¤¤¡C ³o¨âºØÃĪ«¬Ò¬°¤J¤f§í¨î¾¯¡]entry inhibitors¡^¡A¨ä¤¤¤§¤@¬O¤@ºØ§ÜÅé¡A¥²¶·¥Hª`®g¤è¦¡¨Ó¬I¥´¡A ¥s°µibalizumab¡C ³oºØÃĪ««D±`©_¯S¤§³B¦b©ó¡A¥¦¬OªþµÛ¦bCD4¤W¡C ibalizumab µLªkªý¾×¯f¬rªþµÛ¦bCD4¤WÀY¡A¦ý¬O¥¦¯àªý¤î¯f¬r±µµÛ¤U¨Ó«I¤JCD4¡C ¹êÅçµ²ªG¬Ý°_¨Óibalizumab¦ü¥G¤£·|¼vÅT¨ìCD4 ²Ó­Mªº¥¿±`¥\¯à¡C ¸g¹L³\¦hÁ{§É¸ÕÅçÅã¥Üibalizumab ¹ï©óÀ£¨î¯f¬r¶q¦³·¥¬°ÅãµÛªº¥\®Ä(significant effect)¡C ¦]¦¹¥L¬O¤@ºØ±j®Ä (highly active)¡A¦Ó¥B¡¯­@¨ü©Ê«D±`¦n(very ¡¯well tolerated)ªºÃĪ«¡C ·f°t¨ä¥L¦³¤ÏÀ³ÃĪ«¤@°_¨Ï¥Î¡Aibalizumab ¯à°÷À°§U¦h­«§ÜÃĩʯf±w¼W¥[À£¨î¯f¬rªº¾÷·|¡C

¡¯well tolerated ­@¨ü©Ê¨}¦n ¯à°÷§Ô¨ü¡A©Î¬O¹ï§Ü¡]¤@ºØÃĪ«©Î­¹ª«¡^ªº§@¥Î¦Ó¤£·|²£¥ÍÄY­«ªº°Æ§@¥Î©ÎªÌ¬O¤£µÎªAªº·Pı¡C

The other drug, which is also an entry inhibitor, doesn¡¦t bind to a cell protein. It binds to the virus envelope. That¡¦s a drug called fostemsavir. That drug is being tested in salvage therapy trials. It¡¦s being combined with other active agents. Similar to ibalizumab, it has been shown to be both highly active and well tolerated. And when given in the right combination, it can lead to sustained virologic suppression. It¡¦s called an attachment inhibitor, in terms of the way it works. It may not be as active against all viruses because there¡¦s so much variation in envelope. But, at least for the majority of the viruses that we see most commonly in the United States, it seems to be pretty active.

¥t¤@ºØÃĪ«¡A¥¦¤]¬O¤@ºØ¤J¤f§í¨î¾¯¡A¨Ã¨S¦³ªþµÛ¦b¤@ºØ²Ó­Mªº³J¥Õ½è¤W¡A¦Ó¬OªþµÛ¦b¯f¬rªº²Ó­M½¤¤W­±¡C ³o¤@ºØÃĪ«ºÙ¤§¬° ¡¯fostemsavir¡C ²{¦b¥¿¦b¹ï¸ÓºØÃĪ«¹B¥Î¦b­«¯gªvÀø¤W¶i¦æ´ú¸Õ¡C ¦¹ºØÃĪ«²{¥¿»P¨ä¥L¦³®Ä¦¨¤ÀÃĪ«¦X¨Ö¨Ï¥Î¡C »Pibalizumab ¬Û¦ü¤§³B¬O¡Afostemsavir ³QÃÒ¹ê¦P¼Ë­Ý¨ã±j®Ä¥H¤Î¨ã¦³·¥¨Î­@¨ü©Ê¡C ·f°t¦³®ÄªºÃĪ«¦X¨Ö¨Ï¥Î¡A¯à°÷¦³®ÄÀ£¨î¯f¬r¶q¡C fostemsavir³QºÙ§@¬O¤@ºØ¡¯ªþµÛ§í¨î¾¯¡]¡¯attachment inhibitor¡^¡A¦WºÙ¬O¥H¥¦§@¥Î¤è¦¡¦Ó¨Ó¡C µM¦Ó¥Ñ©ó²Ó­M½¤¥»¨­¦³«D±`¦hºØªºÅܤƧΦ¡¡Afostemsavir¨Ã«D¹ï§Ü©Ò¦³ºØÃþ¯f¬r³£¦³®Ä¡]¾÷²v¬ù¬°50-50¡^¡C µM¦Ó¡A¦Ü¤Ö¹ï©ó¦b¬ü°ê§Ú­Ì³Ì±`¨£ªºµ´¤j¦h¼Æ¯f¬r¦Ó¨¥¡Afostemsavir ¦ü¥G¬OÆZ¦³®Äªº¡C

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