Top drug innovations: 2008 edition
In what has become an annual tradition, I give you my totally subjective choices for the top drug innovations of 2008. In order to qualify the innovation must have been first available for salein the US or EU during 2008. Sadly, it’s slim pickins again this year, with only seven finalists, but 2009 looks to be a better year.
1. (Tie) Romiplostim (Nplate, Amgen) and Eltromopag (Promacta, GSK). Both drugs are thrombopoeitin receptor agonists indicated for second-line treatment of refractory, chronic Idiopathic Thrombocytopenic Purpura. The hackneyed phrase “paradigm-shift” has been applied to the TPO-agonist class, as it represents a potential major departure in the treatment of this uncommon, costly disease. The closely spaced market appearance of the first two class members–essentially a tie to the US market–starkly illustrates the continued erosion of market exclusivity for therapeutic-class pioneers. Further competition in the class is expected shortly. If I had to give an innovation edge to one of these two pioneers, my vote would go to Promacta because it is orally available, while Nplate is administered subcutaneously. A potential for marrow fibrosis with both drugs has led FDA to require fairly stringent REMS (risk evaluation and management strategies), probably slowing the adoption curve for the class. On the other hand, I anticipate a fairly quick expansion to off-label use, as the drugs prove themselves safe and cost-effective.
3. Sapropterin (Kuvan, Biomarin). The first drug approved in the US to treat Phenylketonuria, sapropterin is a synthetic tetrahydrobiopterin, a cofactor for the deficient/damaged enzyme phenylalanine hydroxylase (converts phenyalanine to tyrosine). Kuvan isn’t a cure for PKU, it works in less than 50% of patients, and response to the drug can’t be predicted with currently available theranostics. So why is it a top innovation? Because, it’s the first non-dietary treatment for PKU that offers a chance for thousands of PKU patients to eat more normally without exceeding toxic phenylalanine levels, thereby making compliance with a low-phenylalanine diet more likely. It’s a small step forward, but it’s a definite step.
4. Alvimopan (Entereg, Adolor). A periphery-restricted µ-opioid–receptor antagonist indicated for reducing GI recovery time following bowel resection with anastomosis (i.e. reduction of postoperative ileus). Entereg was finally approved by the FDA after its third-cycle review; the initial NDA was submitted June 2004, and the drug was approved May 2008. Cardiovascular safety concerns had precluded earlier approval. Despite the delay, Entereg was the first peripherally acting µ-opioid–receptor antagonist to be approved in the US , and is the only one shown to improve GI recovery time following bowel surgery. The other recently approved drug in this class, Relistor (below), appears not to work well in this condition.
5. Methylnaltrexone (Relistor, Progenics/Wyeth) periphery-restricted µ-opioid–receptor antagonist for opioid-induced constipation in advanced illness. I separated these two drugs, because Entereg works to prevent post-operative ileus, whereas Relistor does not (at least based on a preliminary assessment).
6. Etravirine (Intelence, Tibotec). Intelence is nonspecific NNRTI that is indicated for use in combination with other agents for treatment-experienced adults with HIV-1 infection. This NNRTI was discovered as part of a program aimed at targeting HIV strains with mutations that have rendered other NNRTIs impotent. It is the first NNRTI to demonstrate activity in patients who have previously failed treatment with other NNRTIs. That said, the drug is susceptible to an accumulation of “nonclassical” HIV-1 mutations, which can render it ineffective with chronic use, particularly if given without other effective therapies (see this review for details).
7. Lacosamide (Vimpat, Schwarz Biosciences). Rounding out this year’s list, Vimpat is a novel antiepileptic for adjunctive therapy of partial-onset seizures in adults. There is a clear need for treatments of drug-refractory seizures. Vimpat addresses this need to some extent, reducing the frequency of seizures when used as adjunctive therapy in drug-refractory partial-onset seizures. Unfortunately, however, only ~5% of patients remained seizure-free during a 12-week maintenance period (details here), highlighting a need for further innovations in this area.
January 2nd, 2009 at 2:03 pm
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