Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

Agency sanctioned 35 new medications including two with companion diagnostics.

During 2011, FDA approved 35 new medicines. This was, according to the agency, among the highest number of approvals in the past decade, surpassed only by 37 approvals in 2009.

Of the 35 drugs given the go-ahead, two were approved with a molecular test, making them the first companion drug-diagnostic sanctions. Such tests will be key drivers of drug development in the future. Seven newly sanctioned medications provided advances in cancer treatment, and 10 were for orphan diseases. Notably, the first new therapy for lupus in 50 years was green-lighted this past year.

In terms of how efficiently the FDA was able to do its job, three cancer drugs were given the go-ahead in less than six months. Two-thirds of all the drugs sanctioned last year were completed in a single review cycle and 34 were approved on or before the agreed-upon review time targets.


On August 26, FDA green-lighted Pfizer’s Xalkori to treat locally advanced and metastatic non-small-cell lung cancers that express an abnormal anaplastic lymphoma kinase (ALK) gene. The agency approved the drug along with a diagnostic test for the ALK gene abnormality, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit. Up to 7% of those with NSCLC, typically patients without a history of smoking, have the gene abnormality.

Pfizer says the tyrosine kinase inhibitor will cost $9,600 a month or $115,000 for patients who take it for a year. In clinical trials, the average duration of treatment was between 22 and 32 weeks, but because the drug appears to extend patients lives, many may be on it for far longer than that.

The other drug-diagnostic approval was Roche’s Zelboraf to treat metastatic or unresectable melanoma and the Cobas 4800 BRAF V600 Mutation Test. Zelboraf, an oral kinase inhibitor, acts by blocking the function of the V600E-mutated BRAF protein. The mutation is present in about half the patients with late-stage melanomas.

The diagnostic will cost around $150 and the drug about $9,400 per month. It assumes, based on progression-free survival data from clinical studies, a treatment course of roughly 6–8 months.

In 2011, FDA sanctioned another drug for metastatic melanoma, Bristol-Myers Squibb’s Yervoy. This mAb therapeutic acts by binding to and blocking the actions of the cytotoxic T-lymphocyte antigen 4 (CTLA-4).

The antibody can cause significant side effects, however, including fatigue, diarrhea, skin rash, endocrine deficiencies, and colitis. Severe to fatal autoimmune reactions were seen in 12.9% of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.

Yervoy achieved sales of $121 million in the third quarter of 2011, with ISI Group analyst Mark Schoenebaum commenting that the number was $17 million above Wall Street projections. Bristol-Myers Squibb got Yervoy as part of its 2009 acquisition of Medarex.

Some analysts see obstacles ahead for Yervoy, which costs $120,000 for a full course of treatment, in the form of resistance from regulators overseas. Last October, the National Institute for Clinical Excellence recommended that at a cost of about £80,000, Yervoy “could not be considered a cost-effective use” of health funds. A final decision is expected after a public consultation.

Hepatitis C

Two drugs for the treatment of hepatitis C won approval in May, 2011—the first new drugs approved for the viral disease in 20 years: Vertex’ Incivek (telaprevir) and Roche’s Victrelis. Both drugs interfere with the ability of HCV to replicate by inhibiting a key viral enzyme (NS3/4A serine protease).

The FDA said that it may be possible to shorten Incivek treatment from 48 weeks to 24 weeks in most patients. Given the toxicity of hepatitis C therapies, a shortened treatment period represents a significant advance.

Incivek was widely expected to generate the biggest sales: $4 billion worldwide by 2016, with Vertex taking in $1.75 billion in the U.S. following a peak of $2.21 billion in 2014. Telaprevir’s market advantage, analysts said, will come from its slightly better efficacy and side-effect profile. Victrelis’ anemia side effect will require management with erythropoietin-stimulating agents in many cases. Further telepravir performed well in the null responder population, which had proven controversial for Victrelis.


Last year also saw approval of the first new drug developed for lupus in 50 years, Human Genome Sciences (HGS) and GlaxoSmithKline’s Benlysta. The mAb therapy was green-lighted on March 9, 2011, for adult patients with active, autoantibody systemic lupus erythematosis who are receiving standard therapy.

Benlysta targets the B-lymphoycte stimulator (BLyS) protein and may reduce the number of abnormal B cells thought to contribute to the disease. Analysts predict sustainable, long-term blockbuster potential for Benlysta, with projected sales of $2 billion to $4 billion annually.

Good Year for FDA

In looking over 2011 drug approvals, FDA did a pretty good job despite the carping from the pharma industry, financial community, and some patient advocacy groups.

FDA’s new cancer drug sanction process is consistently faster than the EMA, according to Samantha A. Roberts, Jeff D. Allen, and Ellen V. Sigal, affiliated with Friends of Cancer Research. They conducted a review and analyses of data available on FDA and EMA websites for the period between 2003 and 2010.

Among 35 new cancer drugs reviewed by FDA, 32 were approved, 20 of them within 184 days. EMA, on the contrary, approved only 26 of these new cancer drugs within an average time of 350 days. “Contrary to repeated public assertions, we found that new oncology medicines are consistently available in the United States before they are in Europe, and they are more likely to be approved by the FDA than by the EMA,” wrote the authors.

The report went on to say, rightly so, that its findings reinforced the need for strong financial and public support of the FDA so that “such medicines can continue to be made available speedily to patients in need.”

Patricia F. Dimond, Ph.D. ([email protected]), is a principal at BioInsight Consulting.

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