Encouraging signs from quality of new drugs approved so far in 2011

Widespread talk of the demise in R&D productivity could be overdone. Regulatory approval yesterday for Roche and Daiichi Sankyo’s novel melanoma drug Zelboraf (vemurafenib) brings the new drug tally so far this year to 24, well on the way to beating the 26 new agents approved in 2010.

Yet it is not just the quantity of new product approvals which is encouraging, the quality of drugs approved this year could be the best in 15 years and builds on a decent showing last year (R&D productivity needs to assess quality, not just quantity, March 10, 2011). On the basis of cumulative US sales five years after approval, the class of 2011 could rack up an impressive $14.6bn, with at least five potential blockbusters reaching the market (see tables below). Of course 2011 could be a blip – at least eight of this year's class with combined fifth-year sales of $5bn should have been approved some time ago – and return on R&D investment remains questionable. But the numbers are certainly encouraging and add fresh fuel to the R&D productivity debate.

Encouraging numbers

The table below shows the top ten new molecular entities approved so far this year, ranked on US sales in 2016 (contact [email protected] for the full list of 24 new agents).

The first four – Benlysta, Incivek, Xarelto and Brilinta – are all predicted to be blockbusters in the US market alone by 2016, while Yervoy should easily breach $1bn in terms of global sales.

The total combined fifth-year US sales for all 24 new drugs approved so far this year is $12.3bn, easily above the annual average from the last 14 years of $8.8bn, as highlighted in a recent EvaluatePharma report – World Preview 2016.

Top 10 FDA approvals for NME drugs YTD 2011 (ranked on US sales in 2016)
# FDA Approval Date Product Generic Name Therapeutic Category Pharmacological Class Technology Company(s) Originator Review Status 5th Yr (2016) US sales ($m)
1 09-Mar-11 Benlysta belimumab Immunosuppressant Anti-B lymphocyte stimulator (BLyS) MAb Monoclonal antibody Human Genome Sciences/GlaxoSmithKline Cambridge Antibody Technology Priority review 1,748
2 23-May-11 Incivek telaprevir Anti-viral NS3-4A protease inhibitor Small molecule Vertex Pharmaceuticals Vertex Pharmaceuticals Priority review 1,736
3 01-Jul-11 Xarelto * rivaroxaban Anti-coagulant Factor Xa inhibitor Small molecule Bayer/Johnson & Johnson Bayer Standard 1,497
4 20-Jul-11 Brilinta * ticagrelor Platelet aggregation inhibitor P2Y12 antagonist Small molecule AstraZeneca Astra Standard 1,109
5 25-Mar-11 Yervoy * ipilimumab Anti-neoplastic MAb Anti-CTLA4 MAb Monoclonal antibody Bristol-Myers Squibb Medarex Priority review 874
6 25-Feb-11 Edarbi azilsartan medoxomil Angiotensin II antagonists Angiotensin II antagonist Small molecule Takeda Takeda Standard 623
7 17-Aug-11 Zelboraf vemurafenib Other cytostatic B-Raf kinase inhibitor Small molecule Roche/Daiichi Sankyo Plexxikon Priority review 605
8 21-Jan-11 Viibryd * vilazodone hydrochloride Anti-depressants  SSRI & 5-HT1A partial agonist Small molecule Clinical Data/Forest Laboratories Merck KGaA Standard 598
9 28-Feb-11 Daliresp * roflumilast Bronchodilator PDE4 inhibitor Small molecule Nycomed/Forest Laboratories Altana Standard 578
10 28-Apr-11 Zytiga abiraterone acetate Hormone therapy 17-alpha-hydroxylase/C17,20 lyase inhibitor Small molecule Johnson & Johnson The Institute of Cancer Research Priority review 572
Other 14 products 2,343
Total potential 5th yr US sales 12,283
* product experienced significant delays due to clinical and regulatory setbacks

However, it is important to note that five of the top ten products – Xarelto, Brilinta, Yervoy, Viibryd and Daliresp – all experienced delays in reaching the market, to varying degrees. Yervoy, Viibryd and Daliresp all spent a longer time in the clinic than would normally be expected, while Xarelto could have gained FDA approval two years ago.

The other delayed products are Nulojix, Potiga and Horizant, all gaining approval this year having previously been rejected by the FDA.

The high approval rate so far in 2011 is therefore overinflated and benefitting from prior setbacks to these products. It is true that every annual new drug approval class will feature products that should, under normal circumstances, have already reached the market, but the suspicion is that 2011 is benefitting more than most.

In the bag

As for how many more new drugs might be approved by the FDA this year, a review of EvaluatePharma’s pipeline data suggests just four significant new products are scheduled to receive a regulatory decision by the end of the year.

Most imminent is Seattle Genetics’ Adcetris which should gain approval within the next couple of weeks, having already won the support of an advisory committee (Panel backs Adcetris but keeps leash short, July 15, 2011). By late November and early December another three new agents could win regulatory support: Eylea, ruxolitinib and crizotinib.

Potential FDA approvals for NME drugs in rest of 2011
# Product Generic Name Therapeutic Category Pharmacological Class Technology Company(s) PDUFA date 5th Yr (2016) US sales ($m)
1 Eylea aflibercept Eye preparations VEGFr kinase inhibitor Recombinant product Regeneron Pharmaceuticals 18-Nov-11 811
2 INCB18424 ruxolitinib phosphate Other cytostatic Janus kinase-1/2 (JAK-1/2) inhibitor Small molecule Incyte/Novartis 03-Dec-11 758
3 Crizotinib crizotinib Other cytostatic c-Met tyrosine kinase & ALK inhibitor Small molecule Pfizer 17-Nov-11 390
4 Adcetris brentuximab vedotin Anti-neoplastic MAb Anti-CD30 MAb-auristatin E conjugate Monoclonal antibody (conjugated) Seattle Genetics 30-Aug-11 383

Bristol-Myers Squibb and AstraZeneca’s dapagliflozin has been excluded from the potential approvals list – although the FDA has yet to make its ruling on the drug, due by October 28, a negative advisory committee vote suggests approval is highly unlikely this year (Dapa doubts validate Bristol-Myers decision to share the risk, July 20, 2011).

Indeed dapagliflozin, and to a lesser extent Eli Lilly’s Alzheimer’s diagnostic agent Amyvid, are the only significant FDA rebuttals so far this year, another factor behind the high approval rate.

Meanwhile Zelboraf and Zytiga gained approval in just three and four months respectively, two of the fastest ever turnarounds by the FDA on record (FDA approval times continue to shorten, March 11, 2011).

Assuming the four remaining new compounds gain approval the tally for 2011 should reach 28, higher than last year but lower than the annual totals for 2008 and 2009. Yet the additional $2.34bn in fifth-year US sales from these four products would bring the total sales potential for 2011 to $14.6bn.

Should this be achieved, the class of 2011 would outperform the stellar graduates from 2004, which included Avastin, Cymbalta, Lyrica and Spiriva, and those from 1998, including Remicade, Singulair, Celebrex, Enbrel and Viagra.

Those are some household names from an era when concerns about R&D productivity were not as high as they are today. It would be premature to suggest the industry might be emerging from the doldrums of 2005-2009 when the quantity and quality of new products was particularly woeful, but the trend from the last two years is certainly encouraging.

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