CP-870893

Although a moderate presence in Europe, with about 25 biosimilars approved and on the market, they haven’t gained traction in the U.S. Even though at least 11 have been approved in the U.S., only about three are available, largely because of business tactics branded drug companies are using to slow down the competition to their typically very high-priced biologic drugs. Broadly speaking, biosimilars are generic versions of biologic drugs. Although not direct copycats, they are “similar,” and as such, require approval processes similar to those of new branded drugs. Although a moderate presence in Europe, with about 25 biosimilars approved and on the market, they haven’t gained traction in the U.S. Even though at least 11 have been approved in the U.S., only about three are available, largely because of business tactics branded drug companies are using to slow down the competition to their typically very high-priced biologic drugs. The U.S. Food and Drug Administration (FDA) even introduced a Biosimilars Action Plan in July to encourage the development of biosimilars. FDA Commissioner Scott Gottlieb indicated that although biologics account for 40 percent of total spending on prescription drugs, less than two percent of Americans use them. Biologics also represent 70 percent of the growth in drug spending from 2010 to 2015. He also complained that the competition for biosimilars was “anemic because consolidation across the supply chain has made it more attractive for manufacturers, Pharmacy Benefit Managers, Group Purchasing Organizations and distributors to split monopoly profits through lucrative volume-based rebates on reference biologics—or on bundles of biologics and other products—rather than embrace biosimilar competition and lower prices.” But, even though the FDA is trying to encourage biosimilar development and adoption in the U.S., there appears to be at least a mini-trend of bigger pharma companies moving away from biosimilar production. The Regulatory Affairs Professionals Society (RAPS ) noted in their Regulatory Focus , that in the last month, three companies have “exited the biosimilar space in one way or another.” Sandoz , the generic drug division of Novartis , stopped its submission for biosimilar rituximab after the FDA asked for more information. Stefan Hendriks , Sandoz’ global head of biopharmaceuticals, stated that he thinks that the market for rituximab “will be satisfied before we can generate the data required.” He was likely referring to the approval of Celltrion and Teva Pharmaceutical ’s rituximab biosimilar. And Pfizer also has a decision pending for its biosimilar for rituximab in the second quarter of next year. Regulatory Focus also reported, “ Boehringer Ingelheim , still locked in litigation with AbbVie over its already-approved Humira (adalimumab) biosimilar in the U.S., said it was abandoning all biosimilar development work outside the U.S. The company also said it will not commercialize its already-approved Humira biosimilar in the EU.” Oncobiologics , which is changing its name to Outlook Therapeutics , recently stopping development of biosimilars for bevacizumab and adalimumab. Is this a trend or a blip? At least one pharma expert, Sarfaraz Niazi , who in 2014 wrote the Handbook of Biogeneric Therapeutic Proteins , thinks so. Largely, he bases that on the history of generic drugs. “This is history repeating from the generics era,” he told BioProcess Insider . “There are so many ways to cut the cost of development and cost of manufacture but because of their mindset and design, Big Pharma cannot do this. They can certainly change both but that requires a monumental shift.” And, essentially, when generic prices plunged, most big pharma companies abandoned generics. And one can see—maybe—how pharma companies observing how difficult it is to gain traction in the U.S., how expensive biosimilar development can be, and how persistent branded-drug manufacturers are in litigating biosimilar competitors, that biosimilars may be more trouble than they’re worth. Niazi argues that while there are big profits in biosimilars, they’re sustainable. “I have projected,” he tells BioProcess Insider , “that once the prices fall to below 60 percent of the current prices, it will no longer be feasible for the Amgens and Pfizers to stay in this market for long.” He also thinks that will be compounded when companies from India and maybe China begin producing biosimilars at significantly lower costs. “Every monoclonal antibody regardless of its use costs about $150 to $200 per gram. This price will drop by another 50 percent once the Indian and Chinese companies start getting approvals; at this stage,” he says, “the prescribers will become redundant and payers will take over.” And the Sandoz, Boehringer Ingelheim and Oncobiologics pullbacks are only the most recent. In 2017, Merck KGaA , Darmstadt, Germany, divested its biosimilars business to Fresenius for $195 million up front. And in November, U.S.-based Merck & Co. (a different company than Merck KGaA) abandoned its Lantus (insulin glargine) biosimilar program after evaluating the anticipated pricing and production costs. Niazi believes big pharma will give up on biosimilars, but smaller niche companies will fill in the hole. It’s possible he’s biased about that, since he founded a biosimilar development company, Karyo Biologics , earlier this year. Despite the apparent gloom and doom, Merck & Co, Sandoz, Pfizer and Amgen all told BioProcess Insider that they didn’t intend to abandon the biosimilar space. Amgen’s director of corporate communications, Kelley Davenport , for example, told BioProcess Insider , “While we can’t comment on our strategy, with 10 biosimilars in our portfolio, Amgen remains committed to its biosimilars program.” So maybe biosimilars, at least in the U.S., are in a transitional period, where big pharma and small niche companies will compete for limited market resources—not unlike generic companies. Not all will survive or decide the market is worth the decreasing profits or regulatory headaches. One thing is certain, though. If a biologic is a big seller, companies will take aim at biosimilars. The world’s top-selling drug, AbbVie’s Humira, is the target for the most biosimilar competition. Seven companies have settled lawsuits with AbbVie to wait to launch their biosimilars to the drug until 2023 in the U.S., and Boehringer Ingelheim may be the eighth. In Europe, four have already launched, and some discounts are as high as 80 percent in some of the Nordic markets. Rick Gonzalez , chief executive officer of AbbVie, told RAPS, “The discounting is coming in 10 points higher than what we would’ve anticipated.” AbbVie expects to lose about 25 percent of Humira sales in Europe and internationally in 2019 as a result of the competition.

SOUTH SAN FRANCISCO, Calif., April 1, 2008 /PRNewswire-FirstCall/ -- Monogram Biosciences, Inc., announced today that it had entered into an agreement with Progenics Pharmaceuticals, Inc. to provide resistance and tropism testing for Progenics' clinical development program of PRO 140, an investigational CCR5 monoclonal antibody being studied for the treatment of HIV. In its ongoing phase 2 studies, Progenics is using Monogram's Tro ) tropism test to screen and monitor HIV infected individuals whose virus uses the CCR5 receptor as a portal of entry to healthy cells. Progenics is also using Monogram's PhenoSense GT(TM) assay to measure viral resistance to drugs from other HIV-1 treatment classes. "We are pleased to play such an important role in the development of this promising new HIV therapy," said Chris Petropoulos, Monogram's Chief Scientific Officer. "Monogram continues to help pave the path for many of the most highly anticipated new HIV drugs in development." Tro a patient selection co-receptor tropism assay that determines whether a patient is infected with a strain of HIV that uses the CCR5 co- receptor, the CXCR4 co-receptor, or a combination of CCR5 and CXCR4 to enter cells. Tro the only clinically validated tropism assay and has been used to select patients in all phase 2 and phase 3 studies of CCR5 antagonists to date. About PRO 140 Progenics announced the start of the phase 2 program for PRO 140 in January 2008. PRO 140 is a novel monoclonal antibody that binds CCR5 and is designed to prevent HIV from entering immune system cells and thereby prevent viral replication, which occurs within the cells. CCR5 is also a receptor for chemokines, members of a family of protein molecules that are secreted by cells as part of the body's natural inflammatory response. Unlike small- molecule CCR5 antagonists, PRO 140 inhibits HIV entry at concentrations that in vitro do not appear to block CCR5's natural function, which includes, in part, directing the migration of immune cells towards sites of inflammation in the body. About Progenics Pharmaceuticals, Inc. Progenics Pharmaceuticals, Inc., of Tarrytown, NY, is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. Principal programs are directed toward gastroenterology as well as the treatment of HIV infection and cancer. The Company, in collaboration with Wyeth, is developing methylnaltrexone for the treatment of opioid-induced side effects, including constipation (oral and subcutaneous formulations) and post-operative ileus (intravenous formulation). In March 2007, the Company submitted a New Drug Application to the United States Food and Drug Administration for the subcutaneous formulation of methylnaltrexone for patients suffering from opioid-induced constipation while receiving palliative care, followed in May 2007 by Wyeth's submission of a Marketing Authorization Application (MAA) in Europe to the European Medicines Agency (EMEA). In the area of HIV infection, the Company is developing the viral-entry inhibitor PRO 140, a humanized monoclonal antibody targeting the HIV entry co-receptor CCR5, which has completed phase 1b clinical studies with positive results. In the area of prostate cancer, the Company is developing a human monoclonal antibody drug conjugate -- a selectively targeted cytotoxic antibody directed against prostate-specific membrane antigen (PSMA), a protein found on the surface of prostate cancer cells. Progenics is also developing vaccines designed to stimulate an immune response to PSMA. About Monogram Monogram is a biotechnology company advancing individualized medicine by discovering, developing and marketing innovative products to guide and improve treatment of serious infectious diseases and cancer. The Company's products are designed to help doctors optimize treatment regimens for their patients that lead to better outcomes and reduced costs. The Company's technology is also being used by numerous biopharmaceutical companies to develop new and improved antiviral therapeutics and vaccines as well as targeted cancer therapeutics. More information about the Company and its technology can be found on its web site at Forward Looking Statements Certain statements in this press release are forward-looking. These forward-looking statements include references to the demand for our testing products, including our Tro the potential use of our Tro for patient selection for the class of HIV drugs known as CCR5 antagonists, the size and timing of Progenics' clinical trials utilizing our products, the outlook for Progenics' investigational drug mentioned in this release and for our testing products, expected protection provided by patents, possible regulation of our products by the FDA. These forward-looking statements are subject to risks and uncertainties and other factors, which may cause actual results to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that physicians may not use a molecular diagnostic for patient selection for CCR5 antagonists or other HIV drugs; whether larger confirmatory clinical studies will confirm the results of initial studies; risks and uncertainties relating to the performance of our products; the growth in revenues; the size, timing and success or failure of any clinical trials for HIV drugs, such as Progenics' drug mentioned in this release; the risk that our Tro may not be utilized for patient use with CCR5 inhibitors; our ability to successfully conduct clinical studies and the results obtained from those studies; our ability to establish reliable, high-volume operations at commercially reasonable costs; expected reliance on a few customers for the majority of our revenues; the annual renewal of certain customer agreements; actual market acceptance of our products and adoption of our technological approach and products by pharmaceutical and biotechnology companies; our estimate of the size of our markets; our estimates of the levels of demand for our products; the impact of competition; the timing and ultimate size of pharmaceutical company clinical trials; whether payers will authorize reimbursement for our products and services and the amount of such reimbursement that may be allowed; whether the FDA or any other agency will decide to further regulate our products or services, including Trofile; whether the draft guidance on Multivariate Index Assays issued by FDA will be subsequently determined to apply to our current or planned products; whether we will encounter problems or delays in automating our processes; the ultimate validity and enforceability of our patent applications and patents; the possible infringement of the intellectual property of others; whether licenses to third party technology will be available; whether we are able to build brand loyalty and expand revenues; restrictions on the conduct of our business imposed by the Pfizer, Merrill Lynch and other debt agreements; the impact of additional dilution if our convertible debt is converted to equity; and whether we will be able to raise sufficient capital in the future, if required. For a discussion of other factors that may cause actual events to differ from those projected, please refer to our most recent annual report on Form 10-K and quarterly reports on Form 10-Q, as well as other subsequent filings with the Securities and Exchange Commission. We do not undertake, and specifically disclaim any obligation, to revise any forward-looking statements to reflect the occurrence of anticipated or unanticipated events or circumstances after the date of such statements. CONTACT: Alfred G. Merriweather, Chief Financial Officer of Monogram Biosciences, Inc., +1-650-624-4576, amerriweather@monogrambio.com; or Jeremiah Hall of Feinstein Kean Healthcare, +1-415-677-2700, jeremiah.hall@fkhealth.com Web site: