Among the 325 products and indications examined in our French edition in 2009:

• 104 were rated based on the advantage they provided over existing treatments:

• 46 were new products (including one authorised for two different indications),
  31 were new indications, 25 were line extensions, and 1 product was examined after longer follow- up, with "A second look".
   
• We rated 62 of these 104 products as representing "nothing new", including 17 of the 25 line extensions.

Fixed-dose combinations: simple novelties
Among the 46 new brand name products, 7 were fixed-dose combinations of existing drugs. Three were mainly intended for the lucrative market in arterial hypertension: amlodipine + perindopril (Rev Prescrire 311), amlodipine + olmesartan (Rev Prescrire 309), and enalapril + lercanidipine (Rev Prescrire 309). Other fixed-dose combinations included: calcipotriol + betamethasone (Rev Prescrire 314) for psoriasis; sitagliptin + metformin (Prescrire Int 101) for diabetes; timolol + brinzolamide (Rev Prescrire 308) for ocular hypertension; and follitropin alfa + lutropin alfa (Rev Prescrire 303) for ovarian stimulation.

Therapeutic advance: rare and modest
As in the previous year, we identified no major advances in 2009: none of the new drugs or indications were rated "Bravo" or even "A real advance" based on our at-a-glance rating system, while only 3 "Offered an advantage".

We were unable to reach conclusions ("Judgement reserved") on the possible clinical value of 6 new drugs or indications, due to the lack of available evidence. Gene therapy failed to live up to expectations in 2009, and no gene-based drugs were authorised in the European Union in 2009 (Prescrire Int 104).

Unacceptable drugs: still too many on the market
The drugs we rate as "Not acceptable" are those with an unfavourable risk-benefit balance in one or more indications. In 2008, 23 (19%) out of 120 new drugs or indications were rated "Not acceptable", as was the case for 19 (18%) out of the 104 new drugs or indications in 2009. Marketing authorisation procedures are still failing to guarantee patients the protection they are entitled to expect from the licensing agencies (Rev Prescrire 304).

Multiple new indications: HIV/ AIDS, psychotropics and cytotoxic agents
In 2009, "slicing up" of indications, a strategy used to increase product visibility, generally without representing a therapeutic benefit for patients, mostly concerned the following products:

• first-line antiretroviral drugs: atazanavir (Prescrire Int 101) and darunavir (Rev Prescrire 309);
   
• psychotropics: aripiprazole for schizophrenic adolescents over 15 years of age, and for acute agitation (Prescrire Int 104 and Rev Prescrire 312); duloxetine for generalised anxiety disorder (Prescrire Int 100); oral risperidone for aggression in Alzheimer’s patients (Prescrire Int 104), and injectable risperidone, following oral neuroleptic therapy (Rev Prescrire 307);
   
• cytotoxic drugs (Prescrire Int 106).

Children: only one significant advance
We examined 11 new paediatric products, new indications or line extensions in 2009. Despite the financial incentives provided for in the European Paediatric Regulation, clinical evaluation of drugs used in paediatrics is still limited. The only therapeutic advance observed in 2009 concerned an antifungal drug, caspofungin, used as a last resort in children with a rare condition, invasive aspergillosis (Prescrire Int 102). The atovaquone + proguanil combination can be helpful in treatment of malaria attacks in children weighing at least 5 kg (Rev Prescrire 304).

However, most drugs approved for paediatric indications in 2009 do not improve the quality of care. Examples include: adalimumab in idiopathic juvenile arthritis (Rev Prescrire 306); atomoxetine in attention-deficit hyperactivity disorder (Prescrire Int 105); insulin glulisine in type 1 diabetes in children 6 years of age and older (Rev Prescrire 304); and lamotrigine for absence seizures (Prescrire Int 104). There were too few data to determine the role of etanercept in plaque psoriasis (Rev Prescrire 309).

Generics: some useful drugs despite anticompetitive practices
A study conducted in 2008 by the European Commission’s Directorate-General for Competition showed that companies developing originator drugs engaged in anticompetitive practices towards generics manufacturers (Rev Prescrire 307). Such practices carry a high cost, for both patients and society as a whole. Thirty-four new generic drugs (marketed or soon to be marketed in France) were examined in 2009. About half of them provided some benefits, including clopidogrel (Rev Prescrire 313), losartan (Rev Prescrire 311), topiramate (Rev Prescrire 311) and valaciclovir (Rev Prescrire 314). In contrast, for two generics the risk-benefit balance is unfavourable: nimesulide (Rev Prescrire 313), a nonsteroidal antiinflammatory drug; and benfluorex (Prescrire Int 105), an amphetamine that was finally withdrawn from the French market in late 2009.

Few biosimilars
Copies of originator biologicals are said to be "biosimilar". In 2009, we examined only 2 such products, based on filgrastim, a granulocyte growth factor (Rev Prescrire 306) and epoetin zeta (Rev Prescrire 304).

A copy of interferon beta was not granted biosimilar status, because it was manufactured in exactly the same way as the originator drug (Rev Prescrire 309).

Whether or not copies of biologicals are considered biosimilar, their risk-benefit balances are comparable to those of the corresponding originator drugs.

©Prescrire April 2010

Source: "A look back at 2009: one step forward, two steps back" Prescrire Int 2010; 19 (106): 89-94.

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