Table 3.
Classification of therapeutic agents according to disease seriousness and degree of therapeutic innovation. As examples of application of algorithm, details are provided in footnotes for a few representative agents
| Scores for therapeutic innovation | ||
|---|---|---|
| Drug for serious diseases ‘a’ | ||
| Important | aa | Carglumic acid, lepirudin*, sodium phenylbutyrate |
| ab | Agalsidase alfa†, agalsidase beta†, botulinum toxin Type B‡ | |
| ba | Adalimumab, alemtuzumab, all anti-HIV drugs, arsenic trioxide, basiliximab, bexarotene, caspofungin, daclizumab, docetaxel, drotrecogin alfa, etanercept, imatinib mesilate, infliximab, miglustat, mycophenolate mofetil, pegvisomant, protein C, rituximab, tasonermin, topotecan, trastuzumab, verteporfin, voriconazole | |
| ac | Riluzole, rivastigmine§ | |
| Moderate | bb | Atazanavir, bimatoprost, bortezomib, brinzolamide, cetuximab, deferiprone, entacapone, eptotermin alfa, fulvestrant, ibritumomab, interferon beta-1a, interferon beta-1b, laronidase, levetiracetam, mitotane, nitric oxide, palivizumab, pramipexole, temoporfin, tolcapone, travoprost |
| c1a | Aprepitant, atosiban¶, capecitabine, fosamprenavir**, insulin glargine**, olanzapine, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b | |
| Modest | c1b | None |
| c1c | Beclaplermin | |
| bc | Alitretinoin, paclitaxel, temozolomide†† | |
| Pharmacological | Anakinra, aripiprazole, bosentan, busulfan, cladribine, cytarabine, darbepoetin alfa, desirudin, dibotermin alfa, doxorubicin, ertapenem, iloprost, insulin lispro, leflunomide, memantine, nateglinide, pioglitazone, repaglinide, reteplase, rosiglitazone, samarium, sevelamer, telithromycin, tenecteplase | |
| Technological | Calcitonin (salmon), epoetin beta, epoetin delta, factor VIIa, ibandronic acid, ibuprofen, imiglucerase, insulin human (rDNA), interferon alfa-2b, interferon alfacon-1, mercaptamine, moroctocog alfa, nonacog alpha, octocog alfa, pregabalin, sirolimus, somatropin, valdecoxib, zoledronic acid | |
| Drug for risk factors for serious diseases ‘b’ | ||
| Important | aa | None |
| ab | None | |
| ba | None | |
| Moderate | ac | None |
| bb | None | |
| c1a | Clopidogrel‡‡, raloxifene | |
| Modest | c1b | Porfimer sodium |
| c1c | None | |
| bc | Celecoxib§§ | |
| Pharmacological | Eptifibatide, fondaparinux sodium, irbesartan, orlistat, rasburicase, telmisartan, teriparatide | |
| Technological | Colesevelam, ibandronic acid, human fibrinogen/human thrombin | |
| Drug for non serious diseases ‘c’ | ||
| Important | aa | Sildenafil |
| ab | None | |
| ba | Tacrolimus | |
| Moderate | ac | None |
| bb | None | |
| c1a | Imiquimod | |
| Modest | c1b | None |
| c1c | None | |
| bc | None | |
| Pharmacological | Apomorphine hydrochloride, eflornithine, lutropin alfa, oseltamivir, tadalafil, vardenafil, zaleplon | |
| Technological | Cetrorelix, choriogonadotrophin alfa, desloratadine, emedastine, follitropin-alfa, follitropin-beta, ganirelix, olopatadine, oxybutynin, parecoxib | |
Lepirudin is indicated in heparin-associated thrombocytopenia (HAT) type II. Note that desirudine, another hirudin-related compound, was classified as pharmacological innovation, owing to a different therapeutic indication.
Both indicated for replacement therapy in patients with Fabry’s disease. We assigned a score ‘b’ to the therapeutic effect considering that the clinical efficacy of these drugs was assessed by means of surrogate end-points, namely the effect on serious debilitating pain and quality of life [11,12], and that they affect only some aspects of the disease [13,14].
Used for the treatment of cervical dystonia, received a score ‘b’ for the therapeutic effect because of the variability of its duration, in particular the tendency of the response to fade over time [15].
Rivastigmine offers only a modest symptomatic benefit in patients with mild to moderately severe Alzheimer’s disease, as stated by the CPMP scientific risk/benefit assessment [16].
Atosiban was scored B (a + c1 + a) owing to its better safety profile in terms of reduced cardiovascular side-effects, although the drug addresses a serious condition (imminent pre-term birth) where previous treatments (e.g. ritodrine) were available [17].
Fosamprenavir and insulin glargine (a + c1 + a) show better kinetics profiles than already existing drugs.
It is approved for the treatment of malignant glioma showing recurrence or progression after standard therapy. The drug appears better tolerated than other agents, but its therapeutic effect was scored ‘c’ owing to its palliative benefit in the approved indication [18]. More recently, however, the addition of temozolomide to radiotherapy for newly diagnosed glioblastoma was shown to result in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity [19,20].
Clopidogrel (b + c1 + a) has a safer profile than ticlopidine with respect to haematological adverse effects, such as neutropenia and thrombotic thrombocytopenic purpura (TTP), although a few cases of TTP [21] and leukopenia [22] have been reported with clopidogrel.
Celecoxib was scored as a modest therapeutic innovation for its indication in the reduction of the number of adenomatous intestinal polyps in familial adenoumatous polyposis, as an adjunct to surgery and further endoscopic surveillance. However, the efficacy of the drug in reducing the risk of intestinal cancer has not been demonstrated and the drug was approved under exceptional circumstances with the commitment of further efficacy studies.