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    Pipeline 2016

    Promising advances seen in cardiovascular disease, advanced cancer

    Editor's Note: This article was first published in the November 2015 issue of Pharmaceutical Executive, another UBM publication. It has been updated to reflect the most current information available at press time.

    Biopharma companies continue to count on the potential in their pipelines and the massive markets with unmet medical needs waiting to be tapped. The successes of several recent launches have produced sales figures so impressive that those who had predicted “the end of the blockbuster era” not long ago have quietly shelved their Carnac the Magnificent turbans.

    A more accommodating regulatory process is helping the cause, to the point that some critics warn that FDA might be too helpful to the industry. Both industry and FDA assure critics that compared to what was seen during the past years of friction, the evolving quality of basic science now means that drugs are coming forward with better safety and efficacy profiles. In addition, trials are better designed and better recruited.

    “FDA standards haven’t changed, but manufacturers are getting better at developing and supporting effective products through approvals,” noted Amy Grogg, senior vice-president of Strategy and Commercialization, AmerisourceBergen Specialty Group.

    The fact that many approvals have been for smaller indications geared to orphan disease populations means that drugs are better targeted to tighter patient groups. In orphan drugs subject to fast-track designation, this represents a  strong move by FDA to support R&D in therapeutic areas that offer immeasurable value to small patient populations while unleashing additional scientific and process innovations that can be applied across disease states, added Grogg.

    FDA has opened itself to dialogue with companies planning trials and submissions by encouraging regular exchanges that eliminate confusion and uncertainty. Drugmakers have been receptive, leveraging the support and making heavy use of specialty- and accelerated-status designations.

    So where does that leave us as we reconnoiter this promising pipeline landscape?  Yes, there are access challenges, ever-higher development costs, and the increasingly vocal — and articulate — denigrators of the profit motive in healthcare. But great scientific advances, some  decades in the making, like the human genome project, have planted seeds of growth that are now yielding visible results in the clinic or in late clinical stages. Scientific and clinical excitement abounds for numerous disease states, especially those that have seen little progress in years. Patient groups are excited — and are more hands-on in the new drug-vetting process than ever.

    See also: New drugs raise hopes

    Table 1

    Alzheimer’s R&D

    Research and drug development in Alzheimer’s disease (AD) continues to bear fruit. A few long-studied compounds are still hanging on, while new entities are sprouting. The market potential would be tremendous for anything, anything that could impact AD progression substantially, so even the slightest sign of progress creates excitement and thus major market interest and volatility.

    For years, the industry has put its hope for a disease-modifying treatment in the amyloid hypothesis. The accumulation of plaques in the brain consisting of amyloid- beta peptide has been investigated as the primary driver in the pathogenesis of the disease and the key target for a cure. The most advanced, and still with a reasonable chance of reaching the market, are two humanized monoclonal IgG1 antibodies targeting amyloid-beta peptide, Eli Lilly’s solanezumab and Biogen’s aducanumab, which have been up and down, and are currently up, sort of, following trial data presented at Alzheimer's Association International Conference in Washington, D.C. last July.

    Solanezumab had all but exited stage left after Phase 3 failures in 2012. But persistence could pay off for Lilly as its extended-look study, EXPEDITION-EXT, showed an altered slope in the decline for patients who received the drug early, compared to those who first received placebo and then got the drug, a delayed-start cohort. Not everyone is impressed, but for the optimistic, a slightly slower decline into AD ranks as a positive sign in a field that clearly needs one. Lilly’s 2,100-patient Phase 3 EXPEDITION 3 trial should see its last patient visit in October 2016, a release date that puts it ahead of the competition.

    Biogen’s aducanumab may benefit, or languish, from sharing the same target as solanezumab, depending on one’s level of optimism and what a second-place finish might mean. It also has recent data for which some are seeing the glass half-full; others are less excited. Optimists will point to the company’s positive results in a 166-patient Phase 1 trial released last March and to the fact that the recent negative analysis could be about getting the right dose. Biogen is willing to wager on the pros and has started the 5-year, Phase 3 program with 1,350 patients. Key data are expected in 2018.

    Roche also saw setbacks, but maintains it amyloid-beta antibody program, gantenerumab, with Phase 3 trials active and estimated completion dates listed in 2019 (Roche’s website lists filing as estimated in 2017+). Roche/Genentech also announced plans to progress to the Phase 3 trial with crenezumab, a humanized monoclonal antibody designed to target all forms of Abeta amyloid, discovered by AC Immune.

    Ultimately, for AD, population dynamics are on the drugmaker’s side. One widely held prediction estimates the proportion of the world's population over 60 years of age doubling by 2050, from about 11% to 22%. The rising impact of AD on the healthcare system may hit the trillion-dollar mark, and a successful market launch of solanezumab could net Lilly $7.6 billion in yearly sales by 2024, according to CNN Money report, citing a BMO estimate. Of course, a discussion on value and analysis of the degree of benefit seen will go a long way to determine the price tag for any new AD treatment. In addition, indications for only patients with mild symptoms may limit the potential label of most value, while early diagnosis and a necessity to treat promptly at the first sign of AD may eventually yield more patients on therapy.

    With this massive market and the potential crisis for caring for so many dependent people in the healthcare system, the number of targets will continue to grow.  But only time will tell whether AD treatments evolve as a step-therapy approach, or whether the field takes a more aggressive trajectory with a combined-drug approach.

    See also: What's in the pipeline for 2014?

    Casey McDonald
    Casey McDonald is Senior Editor, Pharmaceutical Executive.

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