Mecasermin

Origin and structure

Mecasermin is the international non-proprietary name for recombinant human insulin-like growth factor 1 (IGF-1), the growth factor that the liver and other tissues make in response to growth hormone. It is a single chain of 70 amino acids held together by three internal disulfide bridges, with a molecular weight of 7,649 daltons, and its sequence is identical to that of the body's own IGF-1. It is made by Escherichia coli bacteria that carry the human IGF-1 gene.

It was developed for a small group of children who make enough growth hormone, or even more than enough, but cannot answer it by making IGF-1. That condition, severe primary IGF-1 deficiency, is caused by defects in the growth hormone receptor, in the signalling behind it or in the IGF-1 gene; its best-known form is Laron syndrome. Growth hormone cannot help these children, because the step that fails comes after it. Mecasermin gets round the problem by supplying IGF-1 itself. It was approved in the US in 2005. In the EU it received orphan-medicine status on 22 May 2006 and was authorised on 3 August 2007; the authorisation was held first by Tercica Europe, from 2009 by Ipsen Pharma and since August 2025 by the Spanish company Esteve Pharmaceuticals.

Increlex comes as a 4 ml multi-dose vial with 10 mg of mecasermin per ml and benzyl alcohol as a preservative. According to the EU product information, the active substance is made by Lonza in Visp, Switzerland, and batches for the EU market are released by Tjoapack Netherlands in Etten-Leur. Two other forms of IGF-1 that readers often come across, IGF-1 LR3 and IGF-1 DES, are laboratory variants with an altered sequence. They are not mecasermin and have never been authorised as medicines; the last section explains what does and does not carry over to them.

How it works

Normally, growth hormone binds its receptor in the liver and other tissues, which then make and release IGF-1. IGF-1 activates the type 1 IGF receptor, a close relative of the insulin receptor that sits on most cells. At the growth plates near the ends of the long bones it drives the cartilage cells that lengthen the bone; elsewhere it makes cells divide and take up glucose, fatty acids and amino acids to feed growing tissue. In rats that lack IGF-1, recombinant IGF-1 makes the whole body and its organs grow.

Like insulin, IGF-1 lowers blood sugar: it suppresses glucose output from the liver and increases glucose use in the tissues. That is why the labels tie each injection to a meal or snack and leave it out when the child cannot eat. In blood, about 80% of IGF-1 normally circulates in a complex with the binding protein IGFBP-3 and a third protein, the acid-labile subunit, which holds it in the circulation. Children with severe primary IGF-1 deficiency have little IGFBP-3, so they clear injected IGF-1 faster than healthy people. After an injection under the skin, the half-life of total IGF-1 in three young patients was about 5.8 hours; the labels give it twice a day.

Is mecasermin approved?

Yes. As Increlex, mecasermin is a prescription medicine in the EU, the Netherlands and the US, for one narrowly defined condition: growth failure in children with severe primary IGF-1 deficiency. It is not a substitute for growth hormone in children who lack growth hormone, and it is not licensed for adults or for growth once the growth plates have closed.

Research-grade IGF-1 and its analogues are not Increlex. They have no marketing authorisation, are not made under a medicines licence and may not be used in people. The approvals below cover the licensed product only.

• EU: authorised on 3 August 2007 under exceptional circumstances, because the disease is too rare for complete data to be collected, for children and adolescents aged 2 to 18. The diagnosis requires a height at least 3 standard deviations below average, basal IGF-1 below the 2.5th percentile for age and sex, normal growth hormone, and the exclusion of other causes such as malnutrition, an underactive thyroid or long-term treatment with high doses of anti-inflammatory steroids. It is on restricted prescription and under additional monitoring. The CHMP reassesses it every year and last confirmed the authorisation in February 2026. Its orphan status ended in August 2017, after 10 years of market exclusivity, and the EMA lists the supply shortage it first reported in December 2013 as resolved.
• Netherlands: the Farmacotherapeutisch Kompas lists Increlex 10 mg/ml and notes that it is not included in the medicines reimbursement system (GVS). In 2007 the then College voor zorgverzekeringen (CVZ) judged that it had added therapeutic value, as the only registered medicine for the condition, and advised the minister to include it in the GVS under conditions limiting it to the registered indication. The CVZ estimated 44 to 59 potential users in the Netherlands; the manufacturer, working from British data, expected 5 to 6 new patients a year.
• US: approved in 2005 for children from 2 years with severe primary IGF-1 deficiency, defined as height and IGF-1 both at least 3 standard deviations below average with normal or raised growth hormone, or with a deletion of the growth hormone gene and neutralising antibodies against growth hormone. The US label is now held by Eton Pharmaceuticals.
• Sport: the WADA Prohibited List names "insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" in class S2.3, growth factors, prohibited in and out of competition. The Netherlands publishes the list in the Tractatenblad as an appendix to the Council of Europe anti-doping convention; the 2026 list appeared as Tractatenblad 2026, no. 25.

What the research shows

Because the disease is rare, the evidence is small and mostly uncontrolled. The approval rests on five studies, four of them open-label; the one placebo-controlled study had eight patients. Long-term data come from the same children followed for years and from a registry that the EMA made a condition of the licence. Trials in other conditions have been negative or inconclusive.

• Pooled registration studies (EU product information): 92 children with severe primary IGF-1 deficiency received 60 to 120 µg/kg twice daily, and 81 were treated for at least a year. Growth rose from 2.6 cm a year before treatment to 8.0 cm in the first year, 5.9 cm in the second and 4.4 cm in the eighth, each still above the starting rate. The 21 previously untreated children followed to near-adult height ended about 13 cm taller than expected for untreated Laron syndrome, after an average of 11 years. The highest dose gave the most growth, and bone age did not advance faster than age.
• Long-term cohort (Chernausek, 2007): 76 children with growth hormone insensitivity were treated for up to 12 years. First-year growth rose from 2.8 to 8.0 cm a year and depended on the dose. Low blood sugar was reported by 49%, although it also occurred before treatment, followed by thickening of the fat at injection sites (32%) and enlarged tonsils or adenoids (22%).
• Registry data (Ramon-Krauel, 2026): in the global Increlex registry, 102 patients had reached near-adult height by April 2023. They had started at a mean age of 11.8 and were treated for a median of 3.9 years. Height improved by 0.9 standard deviations overall and by 1.4 in children who started untreated and before puberty, almost half of whom reached an adult height in the normal range. Among those with Laron syndrome, 10.5% did.
• Rett syndrome (O'Leary, 2018): in a placebo-controlled crossover trial, 30 girls received 20 weeks of mecasermin and 20 weeks of placebo. Mecasermin did not improve any of the main measures, and some, including a severity score and EEG measures, got worse.
• ALS (Cochrane review, 2012): three randomised trials with 779 people. Two nine-month trials together suggested a small slowing of decline, on low-quality evidence; the largest, in 330 people over two years, found no difference from placebo, and no trial showed longer survival.
• Healthy older women (Friedlander, 2001): in a year-long placebo-controlled trial in 16 women over 60, IGF-1 lifted blood levels from about 66 to about 300 ng/ml, but lean mass, fat mass, bone density, strength, mood and memory did not change. The researchers stopped recruiting after 16 women because no effect was emerging.

Side effects and warnings

The EU product information pools 413 trial patients with IGF-1 deficiency, 92 of them with the severe primary form. The most frequent side effects were headache (44%), low blood sugar (28%), vomiting (26%), thickening at the injection site (17%) and middle-ear infection (17%). Of the 115 patients with low blood sugar, 6 had a seizure from it; eating shortly before or after the injection generally prevented symptoms. The US label counts low blood sugar in 42% of 71 children, severe in 5 and with seizures or loss of consciousness in 4, most often in the first month and in younger children. Enlarged tonsils were seen in 9% of the EU trial patients and snoring in 7%, sometimes with sleep apnoea or fluid in the middle ear; joint pain, an enlarged thymus, heart murmurs and breast growth in boys also occur.

Rarer but serious are raised pressure inside the skull, in 4 patients (0.96%), all of whom recovered, two after stopping treatment and two after restarting at a lower dose; a slipped growth plate at the hip and worsening scoliosis during rapid growth; and allergic reactions, with anaphylaxis estimated at about 0.3% after marketing in the US label. An enlarged heart and leaky heart valves were occasionally found, and the EU product information recommends an echocardiogram before treatment starts and after it ends.

Benign and malignant tumours, including cancers rarely seen in children, have been reported after marketing. Since a December 2019 update, the EU product information rules mecasermin out in children with an active or suspected tumour or a condition that raises the risk of one, warns that the risk may be higher with unapproved use or doses above the label, and says treatment must stop for good if a tumour develops. The US label adds that most cases were reported in children with rare genetic short-stature conditions or other conditions that already carry a higher cancer risk, that tumours were also more frequent at doses above the label or doses that pushed IGF-1 above the normal range, and that it is unknown whether mecasermin causes them. In two-year rat studies mecasermin increased adrenal tumours, and at higher doses skin and breast tumours. Because it contains benzyl alcohol it must not be given to premature babies or newborns, and it is not for use in pregnancy.

Mecasermin versus IGF-1 LR3 and IGF-1 DES: what carries over

IGF-1 LR3 and IGF-1 DES were both made to escape the binding proteins that keep IGF-1 in check. LR3 has 83 amino acids, with arginine in place of the glutamate at position 3 and an extra 13 amino acids at the front. IGF-1 DES, or des(1-3)IGF-1, is IGF-1 without its first three amino acids, glycine, proline and glutamate, which leaves 67; it also occurs naturally and has been isolated from cow's colostrum, human brain and pig uterus. Without the glutamate at position 3, both bind the binding proteins far less, so more of each dose is free to reach the receptor. Neither has been tested in a clinical trial, and no regulator has authorised either.

What carries over is the biology of the receptor. All three act on the type 1 IGF receptor, and the effects the Increlex labels warn about follow from it: low blood sugar, growth of the tonsils, adenoids and other tissue, and the concern that IGF-1 signalling feeds tumours. For the analogues the blood-sugar effect is stronger, not weaker. In pigs and marmoset monkeys the variants lowered blood sugar 2 to 3 times more potently than IGF-1, with IGF-1 DES the most potent of those tested, and kept it down for longer: over four hours the total lowering was 4 to 8 times that of IGF-1. None of these risks has been measured in people for either analogue.

What does not carry over is the dose, the timing and the evidence. The Increlex doses are set per kilogram of body weight for children whose blood is short of binding proteins. IGF-1 DES was about 10 times as potent as IGF-1 on cultured cells, a gain partly kept in animals, where its effects were strongest in the gut, and in animal studies the variants left the blood faster than IGF-1 while their effect on blood sugar lasted longer. The 5.8-hour half-life of mecasermin therefore says nothing about them. Nor does its benefit: Increlex adds height in children who cannot make IGF-1, while in healthy older women a year of natural IGF-1 did not change lean mass or strength. Increlex is also a licensed medicine with a known content per dose; laboratory analogues are not, and the WADA list bans all of them.

Frequently asked questions

Is mecasermin the same as IGF-1 LR3 or IGF-1 DES?

No. Mecasermin is IGF-1 with the natural 70-amino-acid sequence, a licensed medicine made and tested under pharmaceutical rules. IGF-1 LR3 (83 amino acids) and IGF-1 DES (67) are altered forms that bind the blood's binding proteins far less, which made them stronger and longer-acting on blood sugar in animal studies. Neither has been tested in people, so the doses, half-life and safety record of Increlex do not apply to them.

Is Increlex available in the Netherlands?

Yes, on restricted prescription, for children aged 2 to 18 with confirmed severe primary IGF-1 deficiency, with treatment directed by doctors experienced in growth disorders. It is authorised throughout the EU, the Farmacotherapeutisch Kompas lists it, and the EMA lists its earlier shortage as resolved. It is not authorised for adults, for children who simply lack growth hormone, or for building muscle.

Is IGF-1 banned in sport?

Yes, at all times, in and out of competition. The WADA Prohibited List names IGF-1, including mecasermin, and its analogues in class S2.3, growth factors, so IGF-1 LR3 and IGF-1 DES are covered too. In the Netherlands the list is published in the Tractatenblad; the 2026 version is Tractatenblad 2026, no. 25.

Does IGF-1 build muscle?

Not in the human trials so far. In a year-long placebo-controlled trial, IGF-1 raised blood levels in healthy women over 60 to young-adult values but did not change their lean mass, fat mass or strength. In ALS, the largest trial found no slowing of the loss of muscle strength. Its proven use is height in children who cannot make IGF-1.

What is the difference between mecasermin and growth hormone?

Growth hormone works largely by making the body produce IGF-1; mecasermin is IGF-1 itself. It therefore helps children whose problem lies after growth hormone: their growth hormone is normal or high, but their body does not respond with IGF-1. For children who lack growth hormone, the labels state that mecasermin is no substitute. The two also differ in their effect on blood sugar: growth hormone tends to raise it, while mecasermin, like insulin, can lower it.

What is Laron syndrome?

Laron syndrome is the best-known cause of severe primary IGF-1 deficiency: the growth hormone receptor does not work, so growth hormone is normal or high but IGF-1 stays low, and children grow very slowly. It is rare; in 2007 the CVZ estimated 44 to 59 potential users of mecasermin in the Netherlands. In the Increlex registry, children with Laron syndrome gained height on treatment, but only about 1 in 10 reached an adult height in the normal range.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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