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2015 Post-ADA Report
July 01, 2015
The American Diabetes Association (ADA) 75th Scientific Sessions was held in Boston, MA from June 5-9, 2015.
A number of the more prominent topics at this year's conference revolved around safety issues, notably cardiovascular outcomes studies (CVOTs) for DPP-IV inhibitor Januvia (MRK) and GLP-1 agonist Lyxumia (SNY, Zealand), questions about liver safety/triglycerides in the Phase III data for long-acting basal insulin peglispro (LLY), and comments at several session about the issue of diabetic ketoacidosis (DKA) raised by the FDA for SGLT-2 inhibitors.
A couple biosimilar insulins (or 505(b)(2) in the US)--SAR342434 (SNY) and MK-1293 (MRK, Samsung Bioepis)--had first data, and while it was perhaps not too exciting to see how similar they were to their benchmarks products, it was interesting to see different views on their potential impact on insulin prices. Datamonitor Healthcare provides a perspective on the impact of insulin biosimilars, as well as the market implications for Januvia's CVOT, mentioned above.
Intarcia's ITCA-650, a novel mini-pump for 6 to 12 month dosing of GLP-1 agonist exenatide, had details from its first randomized Phase III study. And Phase II data from Baricitinib (LLY, INCY) and NOX-E36 (Noxxon) showed potential for diabetic nephropathy, though it is unclear still whether either drug will move forward.
The report covers a number of other drugs and topics, as well.
Part II of the report will include an analysis from Citeline of industry sponsored studies at this year's ADA, as well as new drugs that have come on the radar. In this report, we include background from Citeline's Pharmaprojects® and Trialtrove® on the diabetes pipeline, top industry sponsors of ongoing and planned trials in Type 2 diabetes, geographic spread of the trials, and trials for SGLT inhibitors.
CONFERENCE HIGHLIGHTS
Incretin's Cardiovascular Outcomes Trials (CVOT)
For our disclosures, please read the BioMedTracker Research Standards.
A number of the more prominent topics at this year's conference revolved around safety issues, notably cardiovascular outcomes studies (CVOTs) for DPP-IV inhibitor Januvia (MRK) and GLP-1 agonist Lyxumia (SNY, Zealand), questions about liver safety/triglycerides in the Phase III data for long-acting basal insulin peglispro (LLY), and comments at several session about the issue of diabetic ketoacidosis (DKA) raised by the FDA for SGLT-2 inhibitors.
A couple biosimilar insulins (or 505(b)(2) in the US)--SAR342434 (SNY) and MK-1293 (MRK, Samsung Bioepis)--had first data, and while it was perhaps not too exciting to see how similar they were to their benchmarks products, it was interesting to see different views on their potential impact on insulin prices. Datamonitor Healthcare provides a perspective on the impact of insulin biosimilars, as well as the market implications for Januvia's CVOT, mentioned above.
Intarcia's ITCA-650, a novel mini-pump for 6 to 12 month dosing of GLP-1 agonist exenatide, had details from its first randomized Phase III study. And Phase II data from Baricitinib (LLY, INCY) and NOX-E36 (Noxxon) showed potential for diabetic nephropathy, though it is unclear still whether either drug will move forward.
The report covers a number of other drugs and topics, as well.
Part II of the report will include an analysis from Citeline of industry sponsored studies at this year's ADA, as well as new drugs that have come on the radar. In this report, we include background from Citeline's Pharmaprojects® and Trialtrove® on the diabetes pipeline, top industry sponsors of ongoing and planned trials in Type 2 diabetes, geographic spread of the trials, and trials for SGLT inhibitors.
CONFERENCE HIGHLIGHTS
Incretin's Cardiovascular Outcomes Trials (CVOT)
- Encouragingly, highly awaited data from Januvia's (MRK) TECOS and Lyxumia's (SNY, Zealand) ELIXA did not reveal any
surprising safety findings.
- Unlike Onglyza and to some extent Nesina, Januvia showed no increase in heart failure hospitalizations. This should be a boost for Januvia, though there are still questions how the FDA will deal with labeling. KOLs we spoke with were uncertain, though one thought the agency would include the issue on Onglyza's label, but not Januvia's. Datamonitor Healthcare discusses the implications regarding competing DPP-IV and SGLT-2 inhibitors.
- A couple commentators did mention numerical imbalances in pancreatitis across TECOS and prior DPP-IV CVOTs, though the differences from placebo were quite small.
- With first details from the Phase III program of LY2605541 (peglispro), LLY touted the drug as the first basal insulin to
consistently
show superiority
over glargine in a pivotal trial with a reduction in nocturnal hypoglycemia, as well. The difference in efficacy was modest, however, and
there was an increase
in overall hypoglycemia when used with mealtime insulin.
- The results would be more compelling if safety were not a big caveat. While some investigators were confident that relative
increases in liver fat and
liver function tests are not a significant safety issue, other observers were not so certain--and the company is still sorting out what they
will need to show to the
FDA for approval.
- Complicating matters, the increase in liver function tests was only partly explained by the increase in liver fat, though there were no Hy's law cases. And while some attributed the difference in triglycerides and liver fat to the fact that comparator glargine actually lowers them, that is not entirely clear.
- The results would be more compelling if safety were not a big caveat. While some investigators were confident that relative
increases in liver fat and
liver function tests are not a significant safety issue, other observers were not so certain--and the company is still sorting out what they
will need to show to the
FDA for approval.
- Biosimilars SAR342434 (SNY) and MK-1293 (MRK, Samsung Bioepis) met equivalence targets in euglycemic clamp studies. Of
course, the longer Phase
III studies are needed to assess antibody formation.
- A speaker at a presentation on the cost of insulin therapy in the US decried the sticker shock from rapid increases and was skeptical about the impact of biosimilars. Another speaker felt biosimilar pricing will depend on payor aggressiveness. Datamonitor Healthcare discusses the expected market dynamics as others, like Basalog (Mylan/Biocon), enter the market.
- Early data from weekly insulins, which sponsors hope to be combined with weekly GLP-1 agonists, sparked debate on their utility.
- Results for the first randomized Phase III trial of the ITCA-650 (Intarcia)—a mini-pump that would only need to be changed every 6 to 12 months-- showed reasonable efficacy. On tolerability, though, there was a somewhat high rate of vomiting, albeit with few discontinuations. Intarcia's booth, with demonstrations of the device, appeared to generate a fair degree of interest, if not at least curiosity.
- First details from HM11260C's (Hanmi) Phase IIb weekly dosing trial showed efficacy at least as good as daily Victoza, with the high
dose performing
somewhat better numerically. The high dose did have a higher rate of vomiting, but that may be reduced through titration. The segment
is
increasingly
crowded, though, and the company still needs to decide on financing further development.
- Data for monthly dosing suggested it could be viable, but it is not clear that efficacy would be as strong as weekly dosing.
- Xultophy (NVO) had details from 3 additional Phase III studies. As expected, in patients failing glargine, there was a benefit on
A1c and lower
hypoglycemia compared to further titration of glargine.
- In combination with oral medications versus placebo, however, a relatively high rate of confirmed hypoglycemia raises the question whether it would not be better to just start with a GLP-1 agonist instead.
- There appears to be a possible imbalance in MACE adverse events, though the difference is small and how that is interpreted will at least partly depend on the CVOTs for the components.
- A number of speakers and attendees were enthusiastic about such fixed dose combos, already using the free components together.
- Most experts and audience members queried were actually not too worried about euglycemic DKA in Type 2 patients, an issue
raised in a recent
FDA alert, though acknowledged more details are needed on the cases. There was understandably more caution in Type 1, though the
complication may be
avoided with sufficient insulin dosing. This is an evolving story and broader usage will depend, of course, on how primary care
physicians react, which will be
impacted by the FDA's conclusions.
- The first case series of euglycemic DKA was published just after the meeting, though unlike the FDA series, the majority of patients had Type 1.
- Despite DKA concerns, some speakers were still optimistic about SGLT inhibitors in Type 1, due to potential benefits. Data presented from Phase II studies of Sotagliflozin (LXRX) and Jardiance (Boehringer, LLY) in Type 1 showed improved A1c without an increase in hypoglycemia (during flexible titration), as well as more time in the target range.
- SaxaDapa FDC, a combination of AZN's SGLT-2 and DPP-IV inhibitors, had supportive, albeit incremental, data, with a positive bioequivalence study.
- Baricitinib (LLY, INCY) and NOX-E36 (Noxxon) both had signals of efficacy in Phase II data, though the results are tentative. The NOX-E36 data had more issues, but potential signs of sustained efficacy. Baricitinib caused anemia at its high dose, though this may be acceptable if the drug does turn out to prevent worsening kidney function.
For our disclosures, please read the BioMedTracker Research Standards.
Indications Covered: |
Diabetes Mellitus, Type I
Diabetes Mellitus, Type II Diabetic Nephropathy Obesity |
Additional Resources: