ADMINISTRATION OF INSULIN INHALATION
An Advisory Committee of the
U.S. Federal Government recommended, on Tuesday, April 1st, 2014,
the approval of a pharmaceutical preparation for the administration of inhaled
insulin. This decision has enormous significance for millions of diabetics; and
vindicates the billion dollar investment dedicated to the development of this
product.
Members of the
Committee of Experts that advises the Food and Drug Administration, suggest
that the pharmaceutical insulin formulation for inhalation, registered as
Afrezza® by its manufacturer, MannKind Corporation, would be useful to many
patients, even when therapeutic efficacy is less than that of the injectable
pharmaceutical insulin preparations available today.
After voting,
Robert J. Smith, an endocrinologist at the Alpert Medical School of Brown
University, who acted as head of the Advisory Committee of the FDA, said
"this presentation of insulin will be useful to patients who can not gain
control their blood sugar with different formulations of injectable
insulin".
The Committee
decided, by 13 votes in favor to 1 against, to recommend the approval of
Afrezza® for the treatment of type 1 diabetes; but it was not unanimous with respect
to its use in type-2 diabetes.
The favorable
recommendation of the Committee of Experts surprised the FDA itself, which in a
previous review had defined Afrezza’s effectiveness as “marginal”, and
considered that its use was risky. Furthermore, the FDA had rejected two
previous applications by the manufacturer, MannKind Corporation. In both cases,
the FDA required that additional clinical trials were carried out.
The Committee of
Experts, meeting in Hyattville, Maryland, United States, assessed the risk of the
continued exposure of the lungs to insulin was a predisposing factor in lung
cancer. [Remember that insulin is a growth factor (1)]. During
clinical trials, an increased incidence of lung cancer was observed in the
group treated with Afrezza®, as compared to the control group (treated with a
placebo inhaler). However, the Committee assessed this risk as "statistically
insignificant”. The manufacturer, MannKind Corporation, is obliged to conduct
clinical trials to evaluate this risk.
It is expected
that the Afrezza® could be authorized by the F.D.A. this year (2014), taking
into account that the FDA does not normally contravene the recommendations of
its Advisory Committees; although there are notable exceptions.
MannKind
Corporation has its headquarters in Valencia, California, USA. It was founded
by Alfred E. Mann (now 88 years old), a dynamic businessman in medical and
aerospace technology. He had previously founded the Company, MiniMed, which
developed insulin pumps for diabetics. This company was sold to Medtronic for $
3 billion in 2001. Alfred E. Mann also founded companies that developed
pacemakers and cochlear implants.
Alfred E. Mann
spent much of his vast fortune (estimated by Forbes at $ 900 million) in the
patronymic Company, MannKind Corporation, in the quest for a clinically effective
formulation of inhaled insulin. He has a 40% interest in the Company, whose
initial capital was $2.3 billion.
Even if Afrezza®
gains the approval of the FDA, it will probably not be a commercial success,
because MannKind Corporation would have to associated itself with a
multinational pharmaceutical Company in order to be able to market the product properly.
Skepticism about
the future of Afrezza® is rooted in the experience of the U.S. multinational
Pfizer. In 2006, Pfizer gained the approval of inhaled insulin, registered in
many countries as Exubera®. The promising commercial expectations of Exubera® [2]
were dashed just two years after its introduction in clinical practice. The
cost of its failure meant a $2.8 billion loss
for Pfizer.
The two large
pharmaceutical companies that have been linked to insulin, the Danish Novo
Nordisk, and the American Company Eli Lilly, also abandoned their plans to
develop inhaled insulin preparations.
Alfred E. Mann does not
desist in his enthusiasm, declaring that Afrezza® is much easier to use than Pfizer’s
inhaler (Exubera®), which was approximately the size of a tennis ball, while
Afrezza® is smaller (the size of a whistle) and fits in the palm of your hand.
Moreover,
MannKind Corporation declares that insulin inhaler has an even more rapid onset
of action than rapid-acting insulin preparations. FDA experts do not share this
view, doubting the manufacturer’s statements.
These claims, based on the results of the main clinical phase I study, showed
that Afrezza® resulted in fewer cases of hypoglycemia due to its lower
efficiency, compared to rapid-actions injectable insulin.
In the clinical
trial, conducted upon patients with type 2 diabetes, Afrezza® proved more
effective tan the inhaled placebo, but its effect was considered 'modest' when
compared to the results obtained using many anti-diabetic drugs.
MannKind
Corporation argued that inhaled insulin may be useful in delaying the need to
initiate insulin therapy in many patients with type-2 diabetes, and could
reduce the number of daily injections necessary in patients with type-1diabetes.
April, 14th, 2014
López-Tricas JM MD
Hospital
Pharmacist
Farmacia
Las Fuentes
Florentino
Ballesteros, 11-13
Zaragoza
PO 50002
Spain