Haemophilia A/sialorrhoea: Comparator therapies not implemented, added benefit not proven

July 9, 2018, Institute for Quality and Efficiency in Health Care

Two of the four dossier assessments that were published by the German Institute for Quality and Efficiency in Health Care (IQWiG) on 2 July 2018, and which deal with completely different therapeutic indications, have one notable thing in common: In both cases, an added benefit is not proven due to a lack of suitable study data, although there are randomized controlled trials (RCTs) showing effects of the drugs. The reason: Treatment in the comparator arms of the studies fell short of current standards of care and did not concur with the appropriate comparator therapies (ACTs) specified by the Federal Joint Committee (G-BA) for the early benefit assessments.

Emicizumab for haemophilia A

Haemophilia can be treated either with prophylaxis, or only if needed, for example after a bump or a fall. Emicizumab is the first monoclonal antibody indicated for routine prophylaxis in patients with haemophilia A with factor VIII inhibitors. Coagulation factors, in contrast, are used both for prophylaxis and as needed. Treatment with coagulation factors may cause the development of inhibitors, which requires modification of the . A common approach is the use of so-called bypassing agents, which bypass the usual coagulation cascade and are therefore not affected by the inhibitors. Emicizumab also activates coagulation in a way that is not affected by the inhibitors.

The drugs used for inhibitors so far are injected intravenously, whereas emicizumab is injected subcutaneously once a week. Many patients therefore have high hopes for the new .

The drug manufacturer postulated an added benefit based, among other things, on a randomized controlled comparison between emicizumab and as-needed treatment with conventional preparations in the framework of the HAVEN 1 study. However, the G-BA had explicitly specified routine prophylaxis as ACT because, according to the current state of knowledge, this treatment has advantages over as-needed treatment. Hence no added benefit could be derived from the HAVEN 1 study. The indirect comparisons additionally presented were also unsuitable for this.

Glycopyrronium bromide for drooling

Children and adolescents with chronic neurological disorders such as cerebral palsy often have excessive salivation. Until recently, no drug was approved for this therapeutic indication in Germany. Therapies that help swallow the saliva can lead to improvements, however—these therapies include speech therapy and occupational therapy, for example.

The G-BA specified best supportive care (BSC) as ACT. BSC refers to a supportive therapy, optimized for the individual patient, for alleviation of symptoms and improvement in the quality of life. The manufacturer of the new drug glycopyrronium bromide cited two placebo-controlled RCTs and one further study for the postulated added benefit. However, it could not be inferred from the study documents that the children and adolescents received supportive concomitant treatment. No added benefit could be derived from the third study, which had no comparator arm, either.

Study design should take early benefit assessment into account

"Let me start with a positive aspect: These examples confirm that RCTs can also be conducted in relatively rare diseases, and also in children and adolescents", explains Stefan Lange, IQWiG's Deputy Director. "And the new drugs showed notable effects in these studies. It is all the more regrettable that, even seven years after introduction of the early benefit assessment, the manufacturer dossiers still cite studies in which the control groups are not treated in compliance with the standard of care. The patients in the comparator arms of the studies did not receive the best possible treatment, i.e. prophylactic treatment in the case of haemophilia, and treatments such as speech or occupational in the case of sialorrhoea. These kinds of studies are generally unsuitable for the derivation of an added benefit."

Explore further: HIV-positive children and adolescents: Added benefit of rilpivirine not proven

More information: www.iqwig.de/en/projects-resul … ode-book-v.9393.html

Related Stories

HIV-positive children and adolescents: Added benefit of rilpivirine not proven

April 1, 2016
Under the trade name Edurant, rilpivirine as single agent has been approved already since 2011 for adults who are infected with human immunodeficiency virus type 1 (HIV-1). Since November 2015, HIV-1-infected children and ...

Efmoroctocog alfa for hemophilia A: Added benefit not proven

April 4, 2016
Efmoroctocog alfa (trade name: Elocta) has been approved since November 2015 for people with type A haemophilia. This is an inherited disorder that impairs blood clotting. The German Institute for Quality and Efficiency in ...

Apremilast in plaque psoriasis and psoriatic arthritis: No added benefit can be derived

May 19, 2015
Apremilast (trade name: Otezla) has been available since January 2015 for the treatment of moderate to severe plaque psoriasis or active psoriatic arthritis in adult patients in whom certain pretreatments are not sufficiently ...

Osimertinib in lung cancer: Added benefit not proven

June 20, 2016
Osimertinib has been approved since February 2016 for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). ...

Mepolizumab in severe asthma: Added benefit not proven

May 2, 2016
The monoclonal antibody mepolizumab has been approved since the end of 2015 for the treatment of adults with severe refractory eosinophilic asthma. The German Institute for Quality and Efficiency in Health Care (IQWiG) now ...

Idelalisib in second-line treatment for CLL: Added benefit again not proven

July 6, 2016
Already in 2014, the German Institute for Quality and Efficiency in Health Care (IQWiG) examined in an early benefit assessment whether idelalisib offers advantages over the appropriate comparator therapy for patients with ...

Recommended for you

A molecule for fighting muscular paralysis

November 19, 2018
Myotubular myopathy is a severe genetic disease that leads to muscle paralysis from birth and results in death before two years of age. Although no treatment currently exists, researchers from the University of Geneva (UNIGE), ...

New drug discovery could halt spread of brain cancer

November 19, 2018
The tissues in our bodies largely are made of fluid. It moves around cells and is essential to normal body function.

Scientists trained a computer to classify breast cancer tumors

November 19, 2018
Using technology similar to the type that powers facial and speech recognition on a smartphone, researchers at the University of North Carolina Lineberger Comprehensive Cancer Center have trained a computer to analyze breast ...

Use genetic data to predict the best time of day to give radiotherapy to breast cancer patients, say researchers

November 19, 2018
A new clinical study led by the University of Leicester and conducted in the HOPE clinical trials facility at Leicester's Hospitals has revealed the pivotal role that changing the time of day that a patient receives radiotherapy ...

New dual-action cancer-killing virus

November 19, 2018
Scientists have equipped a virus that kills carcinoma cells with a protein so it can also target and kill adjacent cells that are tricked into shielding the cancer from the immune system.

New blood test detects early stage ovarian cancer

November 19, 2018
Research on a bacterial toxin first discovered in Adelaide has led to the development a new blood test for the early diagnosis of ovarian cancer—a disease which kills over 1000 Australian women and 150,000 globally each ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.