Blockbuster 2.0: Eight Ways to Follow that Leadersz Commercial Strategy ing to Thomson Reuters, there are 11 more pro- jected blockbusters launching in 2015, including Bristol-Myers Squibb’s cancer agent Opdivo and Regeneron/Sanof’s cholesterol agent Pralwent Ironically, pharmaceutical companies’ bigger challenge has not been finding but following block- busters. Whar can these companies do for an encore? How can companies successfully follow their own blockbusters when threatened by rivals’ brands or ‘generic competitors, either before of after pacent Pharmaceutical companies’ bigger challenge has not been finding but following blockbusters expiry? Pfizer's well-documented struggles 10 replace its blockbuster Lipitor highlight the immense challenges that many companies face as they pursue “Blockbuster 2.0." Pfizer tried numerous strategies to.replace or extend the patent life of Lipitor, inelud- ing combining it withthe developmental HDL-rais- ing compound atorvastatin, but ulsimacely failed. GlaxoSmithKline with its respiratory juggernaut Advair/Seretide and Sanofi with its gold standard insulin Lantus are among the many companies cur: rently facing this predicament. ‘There are many reasons why companies fail to follow a blockbuster with a Blockbuster 2.0. First and foremost, a product has become a blockbuster because itis so well received by market stakehold- especially providers and patients. Ircan be very challenging to improve upon the gold standard. Providers and patients trust and rely on the product and often resist switching. For many doctors, p scribing a blockbuster becomes habitual. Payers may have contractual arrangements or financial incentives such as rebates, discouints, or tenders which restrict switching from the blockbuster agent. Branded or generic competitors may offer better of lower-priced alternatives Strategies for sequel A number of pharmaceutical companies however, have demonstrated effective approaches to remedy this situation, Here are eight strategies for follow- ing a company’s own blockbuster: Conversion: The most commonly pursued approach is to convert providers and patients into, users of the company’s next generation blockbuster. “The classic example of this strategy is AstraZencca’s switch from its $6 billion blockbuster heartburn agent Prilosec to Nexium, a closely-elated stereo isomer. According to a 2002 Wall Street Journal report, AZ initiated the “Shark-Fin Project” seven years before the proton-pump inhibitor Prilosec was. scheduled t0 go off-patent. The internal team iden: tified numerous ways to convert Prilosec users to Nexium believers, including conducting head-to- head studies of the two products demonstrating, Nexiuum’s better results in gastro-esophageal reflux disease (GERD); legal and regulatory activities to protect intellectual property rights; an aggressive advertising campaign to switch “the purple pill” positioning from Prilosec to Nexiuuny and a massive direct-to-consumer marketing campaign. Asa result of thishighly controversial approach, AZ overcame branded rivals, prevented generic competition, and successfully established Nexium asa $6 billion suc- cessor heartburn deug. Sanofi is currently borrowing a page from AZ’s Blockbuster 2.0 playbook as it seeks to fend off branded and generic rivals for its market-leading basal insulin Lantus. The company is seeking t0 switch diabetic patients to Touje, is follow-on “next {generation of basal insulin.” The company has con- slucted several head-to-head trials demonstrating the advantages of Tonjeo, featuring a more flexible and sustained dosing profile with reduced hypoglycemic episodes and weight gain. The company is also tak- ing legal actions against potential biosimilar com: petitors and aggressively promoting the product. Despite these steps, analysts expect Tosjeo o gener- ate only a small fraction of Laritus’ $8 billion in annual sales, To further offset Lantus’ expected sales losses to competitors, Sanofi has broadened its dia betes franchise with new products, including devel ‘oping LixiL.an, a combination of Lantus with its new GLP-L agent Lystmiia, and adding MannKind’s Inhaled insulin Afrezza. ‘Combinations: Gilead is an expert in combining products to ensure follow-on blockbuster succes. The company built its HIVIAIDS franchise with its two-fixed dosed combination blockbuster Tr nada, It followed that act with the three-dose bination Blockbuster 2.0 Atriplia, which replaced its predecessor as the world’s best-selling HIV ther apy. Gilead next launched Stribild, a four-ingredi ent single-tablet regimen, which has already achieved blockbuster status, The company isapply ing a similar strategy to its HCV franchise, starting with the mega-blockbuster Sovaldi followed by Harvoni, a combination of Sovaldi and the NS5ACommercial Strategy 33 Securing Growth for the HER2 Franchise st ma i ‘Adjuvant BC eeu ee Established standard of care ll Potential new standard of care Ml Future standard of care ‘ulding onthe blockouster Herceptin for metastatic breast cancer imBC),Rache recently launched two folow-on agents: Kadcyla, an atioody-crug conjugate combining Herceptin and the cytoteac chemotherapy, DMT, and neta tobe used in conjunction with Herceptin or Kedcyla. | | | | 2010-2011 «201220132014 20152016, | | inhibitor ledipasvir. Harvonis inal blockbuster Revlimid as a launched 11 yearsag, Huominahas. sales have already eclipsed the first-line multiple myeloma medi- become the world’s bestselling ‘huge quarterly sales ofthe origi- cine followed by its other agents drug with projected 2015 sales nal molecule Sovaldi Thalomid andlor Pomalyst. exceeding $13 Dillion. ‘Transition: Buildingon market Although Pommalyst is a newer, Acquisition: Failing to find a entrenchment and physician more potent follow-on agent, Cel- TNE blocker to succeed Humira, familiarity of Herceptin formera- gene wants doctors to prescribe AbbVie was forced to go outside static breast cancer, Roche Revlimid first since Pomalyst isthe rheumatology area. The com- launched two follow-on agents: unlikely to achieve the block- pany recently acquired Pharmacy Kadeylatrastuzumabemansine, buster sales ofits predecessor. _clics and its oncology product or T-DM1), an antibody-drug Indications: AbbVie's Humira—_Imbruvica(ibeutinib), the first in conjugate that combines the isthe poster child for maintaining a class of medicines called Bruton HER? inhibition of trastuzumab the highsalesof Blockbuster LOby tyrosine kinase (BTK) inhibitors. (che active ingredient found in leveraging eight different indica- Abbie has publicly committed to Herceptin), and the eytotoxicche- tions, including rheumatoid arthri--_its pipeline-in-pll strategy with ‘motherapy, DMZ; and Perjeta, tis, psoriasis, and Crohn's disease. Imrbruvica, which already has which can be used in conjunction In 2010, Humira US Commercial four of its own FDA-approved with Herceptin or Kadeyla, These Leader Jeffrey Stewart was quoted indications. ‘two follow-on agents anda poten- as saying, “We're the only self Acquistion of potential Block- tial bundling of Roche’s HER2. injectable TNF (tumor necrosis buster 2.0 products or comple- breast cancer drugs represent a factor) inhibitor in the category mentary agents in the same thera- critical anti-biosimilar defense that works across the bones, skin, peutic area isan approach used by strategy for Roche. As shown in andthegut.” Morerecenty,Elaine many companies. For years, AZ. the chartabove, Roche isencour- org, VP, US Immunology at has marketed the $3.5 billion aging oncologists prior to the AbbVie, said “Humira isthe only respiratory blockbuster Symbi- launch of Herceptin biosimilarsto biologic with such breadth ofindi-_cort, an inhaled corticosteroid! ‘transition to using the two new cations." Humira’s U.S. product long-acting beta agonist (IC\ agents instead of Herceptin. label erally lists these eight indi-. LABA). As competitors broad- Prioritization: Somecompanies _cationsasiflisting blockbuster ver- ened their inhaled respiratory sequence next-in-class agents t0 sions 1-1, 1.2, 1.3, ete. Humira portfolios, AZ responded by mak- follow use of the original block- essentially offers “a pipeline in a ing acquisitions to fill the gaps in buster In analysts’ meetings, Cel- product,” to paraphrase AbbVie _ its respiratory portfolio. In 2013, ‘gene has prioritized use ofits orig CEO Rick Gonzalez, Despite being AZ purchased Peat! Therapeutics,3s Commercial Strategy Companies must initiate a Blockbuster 2.0 multi- disciplinary team as soon as they recognize their first compound's blockbuster sales potential STAN BERNARD, NO, ‘MBA, is President of Bemard Associates, Uc, obs! pharmaceutca Incusty competion consutrgf. He can ‘ereace at sBemaraMO@ BernaraAssoaates uccom JANET WELLS ME, Isa Senior Associate at ‘Bernas associates. he canbe reaches atlaretwels@ bomaraassocates ceo ‘whose metered dose inhaler (MDI) development pipeline included a Jonge-acting muscarinic antagonist (LAMA), a LAMAJLABA combi nation, and a triple combination {ICS/LABA/LAMA) for chronic obstructive pulmonary disease (COPD). Alongside Symbicort, this provided AZ. with a full port folio, withthe triple being eyed as a blockbuster on its own, Because the products would not launch for afew years, AZ.also picked up the respiratory portfolio of Almixall and its US partner Actavis, giving AZ an instant boost from LAMA, aclidinium and LAMA/LABA. acliniuny/formoterol in Europe. ‘The Almirall portfolio also con- tains other products, which, when paired with AZ’s novel agents in R&D, could provide future respi- ratory blockbusters for AZ. tigation: Nearly all compa- nies seek to protectandior extend the life of their original block- buster AbbVie has been defending ‘over 200 patents for Hummina prior to its 2016 patent expiry and has sought an injunction to block the European Medicines Agency from releasing detailed clinical erial data. Similarly, Celgene has actively sought to maintain exclu Sivity for Reclimnd beyond its pat- ent expiry in 2019. Given that Revlimid represents the majority ofits sales and profits, Celgene has built a patent fore to protect this cirug from generic rival. Hybridization: Some comps- nies seek ro use several of these strategies simultaneously. GSK ere- ated a new once-daily ICS/LABA (BreoRelvar) to convert users from its blockbuster Advair! Seretide (futicasonefsalmeterol) business, which represents overa quarter of the company’ total pharmaceut- cal revenues. Recognizing the upcoming fragmentation in the ICSILABA classand that BroolRel- ‘ur would note able to replace all oftherevenucs delivered by Ado GSK created a Blockbuster 2.0 portfolio—all produced in the Elipa inhaler, whichis an opt mized version of its popular but older Diskusinholer.GSK acquired a large share in Theravance, part nering with the company to pool RSD assets and to ensore rapid development success. GSK has worked to develop the broadest portfolio in the respira- tory field, offered in a common device platform, that includes the first LAMAILABA to che market inthe US;atrplecombination that could be fist to markets and a novel ICS/LAMA combination targeted fora new indication called asthma COPD overlap syndrome. GSK also usd tigation in Europe to challenge Sandoz as it brought itsown version of salmeterol uti- casone in a purple Diskus-like inhaler to the market. With its landmark studies SUMMIT and SALFORD, GSK is working to vole the respiratory market, pos: sibly carving out cardiovascular mortality asa new indication, and twestalish the haltheare resource utilization benefits of once-daily ‘treatment with the Elipta inhaler Best practices ‘There are at east three key learn- ings from companies who have been challenged to find a Block- buster 2.0: Accept the challenge: Pharma companies and professionals should not underestimate the difficuley of replacing a bil- lion- dollar agent. As these examples demonstrate, many companies have failed to find a successful solution to the Blockbuster 2.0 predicament. Start planning early: Branded rivals will target a potential therapeutic class blockbuster as soon as they feel threat- ened, often as early as devel- ‘opmental Phase Il or III, and. may conduct counter- launches in the pre-launch period. Similarly, companies will seek to acquire a potential block: buster’s active pharmaceuti- cal ingredient in Phase III and no later than at launch in order to initiate their own counter-strategies, Conse- quently, companies must ini tiate a Blockbuster 2.0 multi- disciplinary team or task force as soon as they recog- nize their first compound's blockbuster sales potential This internal team should consist of executive manage- ‘ment, marketing, clinical dis: covery and development, medical affairs, legal, regula- tory, manufacturing, com- petitive intelligence, market research, business develop- ment, and other cross-fune- tional professionals as appro- priate. Use multiple strategies: The internal team should evaluate the potential Blockbuster 2.0 strategies listed here and oth- ers to find the right mix of options and actions. As Pfizer and other companies can attest, Blockbuster 2.0 failure can be a very painful lesson, @ generic