Pharma’s fastest followers revealed

Analysis of me-too drug approvals over time shows trends across therapy areas.

Schemes like US priority review and breakthrough therapy designation aim ultimately to cut approval times, and speed to market has also been improved in recent years by efforts to reduce the FDA’s backlog. But how long does it typically take before a novel mechanism of action sees its second market entrant?

That largely depends on what disease area is being considered, and how hot it is perceived to be. An analysis of EvaluatePharma data suggests that in general second-in-class drugs are emerging with increasing speed, though of course being a fast follower does not in itself guarantee success (see charts below).

This can perhaps best be seen in hepatitis C antivirals, where the first-to-market race between the protease inhibitors Victrelis and Incivek was rendered meaningless by Gilead’s subsequent launch of the polymerase inhibitor Sovaldi.

Still, it cannot be denied that antivirals and oncology are two therapy areas where me-too drugs have followed first-in-class launches with increasing speed. This is surely down to the perception that there is enough potential revenue here for more than one product to play for.

Two recent oncology examples are the checkpoint inhibitors and CAR-T therapy. It was just 16 weeks before the anti-PD-1 MAb Keytruda had a direct competitor in the form of Opdivo, and within three years there were two PD-L1-directed drugs on the US market, too. And just seven weeks separate the US approvals of Kymriah and Yescarta – albeit in different haematology uses for now.

Interestingly, Keytruda and Opdivo’s fortunes have waxed and waned: the Bristol drug swiftly took away Merck’s first-mover advantage, but more recently Keytruda has regained the upper hand, thanks to its dominance in first-line lung cancer.

An even more obvious race to market occurred recently outside oncology, concerning the PCSK9 MAbs Praluent and Repatha, with the former winning by five weeks thanks to a priority review voucher; but it is Repatha that analysts ultimately expect to be the long-term victor in sales terms.

Selected US approvals of oncology drugs and antivirals
Mechanism of action First product Approval date Second product Time lag
Anti-CD20 MAb Rituxan, Roche 26 Nov 1997 Arzerra, Glaxosmithkline 12 years
Anti-VEGFR MAb Avastin, Roche 26 Feb 2004 Cyramza, Lilly 10 years
Proteasome inhibitor Velcade, Takeda 13 May 2003 Kyprolis, Onyx (Amgen) 9 years
HIV integrase inhibitor Isentress, Merck & Co 12 Oct 2007 Tivicay, Glaxosmithkline 6 years
Bcr/Abl fusion protein inhibitor Gleevec, Novartis 10 May 2001 Sprycel, Bristol-Myers Squibb 5 years
BTK inhibitor Imbruvica, Pharmacyclics (Abbvie) 13 Nov 2013 Calquence, Astrazeneca 4 years
SMO antagonist Erivedge, Roche 30 Jan 2012 Odomzo, Novartis 42 months
PI3k inhibitor Zydelig, Gilead 23 Jul 2014 Aliqopa, Bayer 38 months
HDAC inhibitor Zolinza, Merck & Co 6 Oct 2006 Istodax, Celgene 37 months
Alk inhibitor Xalkori, Pfizer 26 Aug 2011 Zykadia, Novartis 32 months
Anti-EGFR MAb Erbitux, Imclone (BMS) 12 Feb 2004 Vectibix, Amgen 32 months
Parp inhibitor Lynparza, Astrazeneca 19 Dec 2014 Rubraca, Clovis 104 weeks
BRAF inhibitor Zelboraf, Roche 17 Aug 2011 Tafinlar, GSK (Novartis) 93 weeks
EGFR inhibitor Iressa, Astrazeneca 5 May 2003 Tarceva, Roche 80 weeks
Anti-PD-L1 MAb Tecentriq, Roche 18 May 2016 Bavencio, Merck KGaA/Pfizer 44 weeks
Hepatitis C polymerase inhibitor Sovaldi, Gilead 6 Dec 2013 Harvoni, Gilead 44 weeks
Anti-PD-1 MAb Keytruda, Merck & Co 4 Sep 2014 Opdivo, Bristol-Myers Squibb 16 weeks
Neuraminidase inhibitor Relenza, Glaxosmithkline 26 Jul 1999 Tamiflu, Roche 13 weeks
HIV protease inhibitor Invirase, Roche 6 Dec 1995 Norvir, Abbvie 12 weeks
Anti-CD19 CAR-T Kymriah, Novartis 30 Aug 2017 Yescarta, Kite (Gilead) 49 days
Multiple tyrosine kinase inhibitor Nexavar, Bayer 20 Dec 2005 Sutent, Pfizer 37 days
Hepatitis C protease inhibitor Victrelis, Merck & Co 13 May 2011 Incivek, Lilly 10 days
Source: EvaluatePharma.

This analysis has been done using EvaluatePharma’s broad pharmacology classifications, and compares the US approval dates of the first two drugs in each class to reach the market. Not all the data match neatly defined trends.

For instance, oncology is lucrative, but the blockbusters Velcade, Avastin and Rituxan did not see me-too competition for nine, 10 and 12 years respectively. While the first is expected soon to be overtaken by Kyprolis in terms of sales, the last two have proved safe from Cyramza and Arzerra's challenges – thanks basically to being better drugs.

In the middle of the pack lie such strategies as Parp, EGFR and BTK inhibition. Imbruvica’s four-year period as the sole BTK inhibitor has given it time to establish a virtually unshakable position, but in EGFR it is a franchise story, with Astrazeneca fighting off Tarceva’s threat to its first-mover, Iressa, through the follow-on launch of the highly successful Tagrisso.

The sellside in time expects Tagrisso sales to outstrip those of Tarceva and Iressa combined, so it is clear that first to market only sometimes means best to market.

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