“Insulin glargine/lixisenatide”的意思、由来-开放百科全书

Insulin glargine/lixisenatide is a combination drug that combines insulin glargine and lixisenatide and is used as second-line treatment for diabetes.

Medical Uses

Insulin glargine/lixisenatide is approved as a prescription for adults with type 2 diabetes mellitus poorly controlled by lixisenatide or basal insulin alone.^[1] According to the American Diabetes Association, combination treatment of a GLP-1 receptor agonist with basal insulin should occur after HbA1C levels remain above target (7% for most type 2 people with diabetes) following use of basal insulin.^[1]

The use of insulin glargine/lixisenatide and lixisenatide-containing products is not recommended for use while pregnant.^[2] There is insufficient data in humans to form a pregnancy risk category for lixisenatide. Animal pregnancy studies have shown potential risks to the prenate, but it is unclear if these risks are related to the drug. It is unknown if insulin glargine and lixisenatide are present in human milk or the effects these drugs would have on breastfed infants.^[2] Potential adverse effects to the mother and child as well as management of diabetes and glucose control should be considered prior to use of Soliqua during breastfeeding.^[2]

Adverse effects

Prior to the approval of insulin glargine/lixisenatide, two studies were conducted to evaluate the safety of the formulation.^[2] Adverse reactions for at least 5% of people taking it were hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infections, and headache. In Study A (N=469), symptoms of hypoglycemia were recorded in 25.6% of people with zero cases of severe symptomatic hypoglycemia. Study B (N=365) had a 40% incidence of hypoglycemic events with 1.1% incidence of severe hypoglycemia requiring assistance.^[2]

Interactions

Lixisenatide and other GLP-1 receptor agonist slow emptying of stomach contents, which may affect the absorption of orally administered medications.^[3] For effective use, oral contraceptives should be taken 1 hour before or 11 hours after taking lixisenatide-containing products.^[4] Acetaminophen and antibiotics are among other drugs that are affected by this action of lixisenatide.^[3]

History

Lixisenatide is a GLP-1 receptor agonist that was created by Zealand Pharma A/S of Denmark;^[5] in 2003 Zealand licensed it to Sanofi which developed the drug.^[6] Lixisenatide was approved by the European Commission on February 1, 2013.^[7] Sanofi submitted an NDA in the US, which was accepted for review by the US FDA in February 2013^[8] but after discussions with the FDA about the cardiovascular safety data included in the package (starting in 2008, the FDA had required stronger CV safety data for new anti-diabetes drugs, following the controversy around the risks of Avandia)^[9] Sanofi decided to withdraw the NDA and wait for the results of a Phase III study that was scheduled to be completed in 2015.^[10]^[11] Sanofi resubmitted the application which the FDA accepted in September 2015, by which time Sanofi had lost the lead in the field of anti-diabetic drugs to Novo Nordisk.^[12] Lixisenatide received FDA approval on July 28, 2016.^[13]

In 2010, Sanofi extended a license agreement it had with Zealand for lixisenatide to allow Sanofi to combine it with insulin glargine, which was Sanofi's best selling drug at the time, with sales of around €3 billion in 2009.^[14] Sanofi planned to start the Phase III trial that year.^[14] Sanofi submitted the new drug application in December 2015 for the combination and spent a $245M priority voucher to gain a faster review, to try to outrace Novo Nordisk’s Xultophy, a similar combination drug of Novo's insulin Tresiba and Novo's GLP-1 agonist Victoza.^[15] Sanofi's application was considered by the same Endocrinologic and Metabolic Drugs Advisory FDA Committee that was considering lixisenatide as a single agent.^[23]^[16] In May 2016 by a vote of 12-2, with several members of the committee expressing reservations about Sanofi's plans to offer two pens with different ratios of insulin glargine and lixisenatide - one for people who had never taken insulin before and one for people who had; there was also concern about how to handle dosing when switching people from a single drug regimen to the combination drug.^[17]^[18]^[19] In August 2016 the FDA told Sanofi that it was delaying a final decision for three months, and asked Sanofi for more data on how people used the delivery devices.^[20] In November 2016, the FDA approved Sanofi’s Soliqua™ formulation (insulin glargine 100 units/mL and lixisenatide 33 mcg/mL).^[21] Soliqua became available in American pharmacies in January 2017.^[22]

Society and culture

Cost

Following FDA approval of Soliqua, Sanofi made a $25 million milestone payment to Zealand.^[23] Zealand may receive additional payments up to $110 million along with receiving royalties on global sales. Royalties paid to Zealand for Soliqua are based on a fixed low double-digit percentage of net sales.^[23]

In January 2017, Sanofi announced that the wholesale acquisition cost (WAC) of a 3 ml pen of Soliqua is $127.^[22] At the average dose used in clinical trials, this amounts to $19.90 per day.^[22]

According to Sanofi's Half-Year Financial Report, the net sales of Soliqua reached €9 million in the first six months of availability in the United States.^[24]

Brands

Insulin glargine/lixisenatide was called HOE901/AVE0010 during development and as of October 2017 had been marketed under the trade names iGlarLixi, Lantus/Lyxumia, LixiLan, and Soliqua.^[25]

References

1. ^{{cite journal|title=American Diabetes Association Standards of Medical Care in Diabetes - 2017|journal=The Journal of Clinical and Applied Research and Education: Diabetes Care|date=January 2017|volume=40|issue=1|page=67|url=http://care.diabetesjournals.org/content/diacare/suppl/2016/12/15/40.Supplement_1.DC1/DC_40_S1_final.pdf}}
2. ^¹²³⁴{{cite book|title=Highlights of Prescribing Information: Soliqua|date=November 2016|publisher=FDA|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208673s000lbl.pdf}}
3. ^¹{{cite book|title=Highlights of Prescribing Information: Adlyxin|date=July 2016|publisher=FDA|pages=7-8|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208471Orig1s000lbl.pdf}}
4. ^{{cite web|title=Soliqua 100/33|url=https://www.drugs.com/pro/soliqua-100-33.html|website=Drugs.com}}
5. ^{{cite journal |pmid=19629885 |year=2009 |last1=Christensen |first1=M |last2=Knop |first2=FK |last3=Holst |first3=JJ |last4=Vilsboll |first4=T |title=Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus |volume=12 |issue=8 |pages=503–13 |journal=IDrugs : the investigational drugs journal}}
6. ^{{cite news|last1=Terry|first1=Mark|title=In Attempt to Bolster Sagging Diabetes Revenue Sanofi Inks Deal with Hanmi Pharma Worth 4 2 Billion|url=http://www.biospace.com/News/in-attempt-to-bolster-sagging-diabetes-revenue/397998|work=Biospace|date=November 5, 2015}}
7. ^{{cite web|title=Lyxumia 10 micrograms solution for injection - Summary of Product Characteristics (SPC)|url=https://www.medicines.org.uk/emc/medicine/27405|publisher=UK Electronic Medicines Compendium|accessdate=21 September 2016|date=2 May 2016}}
8. ^{{cite news|url=https://www.drugs.com/nda/lixisenatide_130219.html|publisher=Drugs.com/PR Newsire|date=19 February 2013|title=Sanofi New Drug Application for Lixisenatide Accepted for Review by FDA}}
9. ^{{cite news|last1=Hughes|first1=Sue|title=FDA Advisory Committee Recommends Cardiovascular Safety Studies for Diabetes Drugs|url=http://www.medscape.com/viewarticle/577059|work=Medscape|date=July 3, 2008}}
10. ^{{cite news|last1=Nainggolan|first1=Lisa|title=Sanofi Withdraws US NDA for GLP-1 Agonist Lixisenatide|url=http://www.medscape.com/viewarticle/810871|work=Medscape|date=September 12, 2013}}
11. ^{{cite news|last1=Humphreys|first1=Andrew|title=Reaching Epic Proportions 2013|url=http://www.pharmalive.com/reaching-epic-proportions-2013/|work=PharmaLive|date=December 1, 2013}}
12. ^{{cite news|last1=Taylor|first1=Phil|title=Sanofi's lixisenatide is back under FDA review|url=http://www.pmlive.com/pharma_news/sanofis_lixisenatide_is_back_under_fda_review_831184|work=PM Live|date=September 30, 2015}}
13. ^{{cite web|title=FDA approves Adlyxin to treat type 2 diabetes|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513602.htm|website=FDA|accessdate=28 July 2016|date=28 July 2016}}
14. ^¹{{cite news|title=Zealand extends Lixisenatide licence with S-A|url=http://www.pmlive.com/pharma_news/zealand_extends_lixisenatide_licence_with_s-a_221376|work=PMLive|date=June 8, 2010}}
15. ^{{cite news|last1=Carroll|first1=John|title=FDA panel backs 2nd diabetes combo, endorses Sanofi’s iGlarLixi|url=http://www.fiercebiotech.com/fda-panel-backs-2nd-diabetes-combo-endorses-sanofi-s-iglarlixi|work=FierceBiotech|date=May 25, 2016}}
16. ^{{cite web|title=FDA Briefing Document Endocrinologic and Metabolic Drugs Advisory Committee Meeting|url=http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM502558.pdf|publisher=FDA|date=May 25, 2016}}
17. ^¹{{cite news|last1=Farooq|first1=Raheel|title=Sanofi SA (ADR) and Diabetes: Things Are Not Working Out|url=http://www.businessfinancenews.com/29092-sanofi-sa-adr-and-diabetes-things-are-not-working-out/|work=Business Finance News|date=May 24, 2016}}
18. ^{{cite news|last1=Nainggolan|first1=Lisa|title=Sanofi's GLP-1/Insulin Combo LixiLan Faces 3-Month Delay in US|url=http://www.medscape.com/viewarticle/867920|work=Medscape|date=August 25, 2016}}
19. ^{{cite web|title=Summary Minutes of the Endocrinologic and Metabolic Drugs Advisory Committee Meeting|url=http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM518186.pdf|publisher=FDA|date=May 25, 2016}}
20. ^{{cite news|last1=Staton|first1=Tracy|title=With FDA delay, Sanofi loses head start in diabetes combo-med rivalry with Novo|url=http://www.fiercepharma.com/marketing/fda-delay-sanofi-loses-head-start-diabetes-combo-med-rivalry-novo|work=FiercePharma|date=August 21, 2016}}
21. ^¹{{cite news|title=Sanofi Receives FDA Approval of Soliqua™ 100/33, for the Treatment of Adults with Type 2 Diabetes|url=http://mediaroom.sanofi.com/sanofi-receives-fda-approval-of-soliqua-10033-for-the-treatment-of-adults-with-type-2-diabetes/|publisher=Sanofi|date=November 21, 2016}}
22. ^¹²{{cite news|title=Sanofi Announces Soliqua™ 100/33 Now Available in the U.S.|url=http://www.news.sanofi.us/2017-01-04-Sanofi-Announces-Soliqua-100-33-Now-Available-in-the-U-S|publisher=Sanofi|date=January 4, 2017}}
23. ^¹{{cite news|title=Zealand reports that Sanofi announces Soliqua(TM) 100/33 now available in the U.S|url=https://globenewswire.com/news-release/2017/01/04/903054/0/en/Zealand-reports-that-Sanofi-announces-Soliqua-TM-100-33-now-available-in-the-U-S.html|publisher=Nasdaq Globe News Wire|date=January 4, 2017}}
24. ^{{cite book|title=Half-Year Financial Report|date=July 31, 2017|publisher=Sanofi|page=50|edition=2017|url=http://en.sanofi.com/Images/50046_2017_Half_Year_Financial_report.pdf}}
25. ^{{cite web|title=Lixisenatide/insulin glargine|url=http://adisinsight.springer.com/drugs/800031725|publisher=AdisInsight|accessdate=23 September 2016}}