From the press release

Forxiga is the first oral medicine approved in Europe as an adjunct to insulin for adults with type-1 diabetes and the first AstraZeneca medicine ever approved for type-1 diabetes

The European Commission (EC) has approved Forxiga (dapagliflozin) for use in type-1 diabetes (T1D) as an adjunct to insulin in patients with a BMI ≥ 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy. 

Elisabeth Björk, Senior Vice President, Head of late Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, said: “Forxiga is the first oral medicine approved in Europe as an adjunct to insulin for people living with type-1 diabetes whose glucose levels are not adequately controlled with insulin alone. We look forward to bringing Forxiga to a patient population that has not had any approved oral medicines available before.”

The approval is based on data from the Phase III DEPICT clinical programme for Forxiga in T1D. The short-term (24 week) and long-term (52 week) data from DEPICT-1, along with the short-term data from DEPICT-2, showed that Forxiga 5mg daily, when given as an oral adjunct to adjustable insulin in patients with inadequately-controlled T1D, demonstrated significant and clinically-meaningful reductions from baseline in average blood glucose levels HbA1c (primary endpoint), weight and total daily insulin dose (secondary endpoints) at 24 and 52 weeks.1,2,3

The safety profile of Forxiga in these T1D trials was consistent with its well-established profile in type-2 diabetes (T2D), with the exception of a higher number of diabetic ketoacidosis (DKA) events in Forxiga-treated patients.

DKA is a known complication for adults with T1D that affects those with T1D more frequently than with T2D.Forxiga is already indicated as a monotherapy and as part of combination therapy in adults with T2D to improve glycaemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise.

Forxiga is currently under regulatory review in Japan and the US for use as an adjunct treatment to insulin in adults with T1D, with a decision expected in the first and second half of 2019, respectively.

About type-1 diabetes 

T1D is a chronic disease in which the pancreas produces little or no insulin. Approximately five percent of people living with diabetes have type-1. The condition is caused by an autoimmune reaction that destroys the beta cells in the pancreas which make insulin.4Different factors, including genetics and some viruses, may contribute to type-1 diabetes.5

About the DEPICT clinical programme

The DEPICT (Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes) clinical trial programme consists of two clinical trials: DEPICT-1 (NCT02268214) and DEPICT-2 (NCT02460978). DEPICT-1 and DEPICT-2 are 24-week, randomised, double-blinded, parallel-controlled trials designed to assess the effects of Forxiga 5mg or 10mg on glycaemic control in patients with T1D inadequately controlled by insulin. All patients were evaluated at week 24 and after a 28-week extension (52 weeks in total). Forxiga 10mg has not been approved for the treatment of T1D.

About Forxiga

Forxiga (dapagliflozin)is a first-in-class, oral once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2) indicated as both monotherapy and as part of combination therapy to improve glycaemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise in adults with T2D. Forxiga has a robust clinical trial programme of more than 35 completed and ongoing Phase IIb/III trials in over 35,000 patients, as well as more than 1.8 million patient-years’ experience.

References

[1]. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24-week results from a randomised controlled trial. Lancet Diabetes and Endocrinol. 2017:5;846-17

  1. Mathieu C, Dandona, P, Gillard, P, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care 2018;41:1938–1946
  2. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: The Depict-1 52 week study. Diabetes Care 2018 Dec; 41(12): 2552-2559
  3. “Diabetes Home.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 15 Aug. 2018, www.cdc.gov/diabetes/basics/type1.html.
  4. Type 1 Diabetes.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 7 Aug. 2017, www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011.

Pressmeddelande  från Astra Zeneca idag

 
 
Nyhetsinfo
 
Kommentar:
1. Den ökade risken för DKA, även och i vissa fall även normoglykemisk DKA (diabetisk ketoacidos), dvs DKA med P-Glukos 10-13 mmol/l, gör att europeisk och svensk läkemedelsmyndighet kommer att kräva av företaget att det tas fram skriftlig information till förskrivande läkare kring försiktighet liksom till patienter som får denna behandling för att fokusera på den potentiellt ökade risken för DKA. 
 
2. Ett ökat fokus kring DKA vid typ 1 diabetes är i sig bra, då det finns en 0-vision kring detta, att patienter generellt med typ 1 diabetes ska kunna undvika att utveckla rDKA genom tillgång till rtCGM och isCGM, även tillgång till blodketonmätning dvs att alla patienter med typ 1 diabetes har tillgång till utskrivna blodketonstickor eller mätning i sin apparat vid glukosmätning, inte bara gravida med typ 1 diabetes och patienter insulinpump - utan alla med T1DM.
 
 
Risk för DKA, innan SGLT2-hämmar-förskrivning, i stora material ligger på 1/100 av patienter med T1DM per år utvecklar diabetisk ketoacidos, och vissa patientgrupper står för en större del, patienter med alkohol- och narkotikamissbruk, anorexi-bulimi, extrem LCHF, ökad risk under graviditet, i samband med svåra infektioner, vid debut av T1DM, vid problem med insulinpump eller insulinpenna, insulinbrist, och i vissa fall är det svårt att hitta någon direkt utlösande orsak.
 
3. I samband med Diabetologiska Vårmötet i Stockholm 13/3 2019 diskuterades, att det kanske rör sig om enstaka procent av typ 1 diabetes-patienter som kan bli aktuella för denna nya behandlingsmöjlighet med SGLT2-hämmare.
 
4. Läkemedelsverket i Sverige kommer också ta del av detta informationsmaterial kring denna nya behandlingsmöjlighet - och kommer också informera när läkemedlet kan förskrivas i Sverige på nya indikation vid typ 1 diabetes.
 
5. Se också den mer utförliga texten från europeiska läkemedelsmyndigheten nederst
Med fet stil har texten kring försiktighet lagts in
Under punkt 1-6 har lagts in speciell hänsyn vid ev framtida insättning av läkemedlet
 
6. FDA, amerikanska myndigheten, har i dagarna avböjt att ge klartecken för sotagliflozin, ett läkemedel med både SGLT1 och SGLT2-hämmar-effekt, dvs läkemedlet blockerar både SGLT1 och 2-receptorerna

https://www.empr.com/home/news/fda-rejects-zynquista-nda-for-type-1-diabetes-treatment/

7. I Japan, Sydkorea och Thailand finns sedan dec 2018 godkänt ipragliflozin, en SGLT2-hämmare, vid T1DM 

 
www red DiabetologNytt
 
 

First oral add-on treatment to insulin for treatment of certain patients with type 1 diabetes

 

EMA’s human medicines committee (CHMP) has recommended for the first time an adjunct treatment to insulin in the form of a tablet for certain patients with type 1 diabetes mellitus.

Dapagliflozin is already authorised in the European Union as Forxiga 1clinical trialsCHMPindication2

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these beta cells, the body cannot maintain proper blood glucose levels in response to daily activities such as eating or exercise. Patients with type 1 diabetes require lifelong insulin therapy.

In spite of improvements in insulins, methods of administration and monitoring of blood glucose, a proportion of patients with the disease are unable to achieve or maintain recommended blood sugar levels with insulin alone. Hyper- and hypoglycaemia and weight gain are common and patients’ life expectancy is still significantly reduced compared to the general population, mainly due to the increased risk of heart disease. Thus, there is a need for new therapies as an adjunct to insulin therapy, to better manage blood sugar levels and other cardiovascular risk factors.

The CHMP's positive opinion is based on data from two Phase III studies including 548 patients with type 1 diabetes mellitus. The main benefit of treatment with dapagliflozin in patients with type 1 diabetes is a combined effect on glycaemic control, weight reduction, effects on blood pressure and reduced variability of glucose levels.

The data presented with this application also show that despite precautionary measures, there is a considerable increase in the risk of diabetic ketoacidosis (DKA), a potentially life-threatening complication.

Because the increased risk is of concern, the CHMP recommends limiting the use in type 1 diabetes mellitus patients as follows:

1. treatment should only be considered in overweight or obese patients with a BMI ≥27 kg/m2.

2. Use of dapagliflozin is not recommended in type 1 diabetes mellitus patients with low insulin requirement.

3. During treatment with dapagliflozin, insulin therapy should be continuously optimised to prevent ketosis and DKA and the insulin dose should only be reduced to avoid hypoglycaemia.

4. This treatment should only be initiated and supervised by specialist doctors.

5. Patients should be able and committed to control ketone levels in their body.

6. They should be educated about risk factors for DKA and how to recognise its signs and symptoms.  

The opinion adopted by the CHMP is an intermediary step on Forxiga/Edistride’s path to patient access in this new indication. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.

 

 
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