Insmed Develops Biologic For Amgen’s Neupogen
2 CommentsBy Ed Silverman // July 10th, 2008 // 9:02 am
In doing so, Insmed apparently becomes the first US company to demonstrate bioequivalence for a follow-on biologic. The next step is for the drugmaker to meet with the FDA in hopes of receiving a green light to proceed with a Phase III study for its INS-19 which, like Neupogen, would combat neutropenia, a common side effect of chemotherapy. Neupogen, by the way, is a $1 billion seller.
A Phase I trial involving 32 patients receiving either a dose of Insmed’s INS-19 or Amgen’s Neupogen found that the way the two biologics interacted with the body was statistically indistinguishable, while the concentration of G-CSF (G-CSF stimulates the production of white blood cells) for the two products were identical, according to Insmed. Here’s the statement. Two years ago, the FDA approved Omnitrope, a follow-on version of a human growth hormone that’s sold by Sandoz.
This comes amid a protracted effort to develop a so-called pathway for the FDA to approve follow-on biologics, which some also call biosimilars. Three bills have been introduced in Washington over the past year, although compromise has been stalled over such issues as data exclusivity, the length of time that brand-name innovators would be granted patent protection, and interchangeability, which refers to the extent to which a follow-on biologic could be substituted for an original biologic.
Whether today’s announcement will add any impetus to breaking the stalemate is unclear. This is an election year, after all…
But Steve Glover, who heads Insmed’s biologics effort, offers cost-conscious legislators an incentive - he says Insmed is prepared to sell its follow-on version of Neupogen for up to 30 percent less than what Amgen charges. Currently, a course of Neupogen can cost between $15,000 and $20,000 a year. Of course, we’re still five years from when INS-19 may be available.
Neupogen “has been approved since 1991 and has had a monopoly for 27 years and we know you’ll see a reasonable discount - 20 to 30 percent - required to get on formularies,” Glover tells us. “We’re more than ready to offer discounts to get on those lists. We’re prepared to do that. We’re more than willing to do that. I can tell you it doesn’t cost near that ($15,000 to $20,000 per course) to develop and manufacture the product. And we have a facilty that’s already up and paid for.”
Dan
Innovation in Pharmacology?
Beginning in the 1970, biopharmaceuticals were being researched for production in those places once called academic institutions. The first biopharmaceutical was a synthetic insulin called Humulin made by Genetech in 1982. Later the rights were sold to Eli Lilly for this insulin. Biopharmas are distant and covert relatives of big pharma, yet become intimate with them more often now than ever before due to dry pipelines of big pharma- GSK and Roche in particular, yet most big pharma examine acquisition of biopharma companies. Over 20 biopharma drugs were approved in 2005, I believe. They are overall very effective treatments for very difficult diseases to manage, as they target specific aspects of certain diseases, which limits side effects experienced by the patient on therapy with a biopharma drug. There are about a dozen of different classes or mechanisms of action of biopharmaceuticals that have about a half of dozen different types of uses that is always increasing, as lablel alterations of biopharmas are requested soon after the approval of a particular medication by ths method. Some cause apoptosis, or cell death of specific tumor cells. Some cause angiogenesis to occur, which means they cut off the blood supply to tumors. Then some biopharmaceuticals have multiple modes of action that benefit certain patient types and their diseases greatly.
Some biopharmas are more noteworthy than others, such as Enbrel, which was originally created for the many forms of RA- arthritis caused by the patient’s immune system attacking their bodies. At one point, demand exceeded supply for this drug greatly, as the efficacy was evident and demand was unexpected by the manufacturer, so Enbrel was sought out by doctors and patients both due to the clinical data verifying the efficacy and benefits of the drug. Enbrel was approved in 1998 and produced from what are called monoclonal antibiodies. In fact, some call the 1990s the biopharmaceutical decade.
Partnering of biopharmaceutical companies and larger pharmaceutical companies began during this decade- however has become more often recently due to the apparent dry pipelines of big pharma. It’s a symbiotic relationship in that big pharma can provide the resources and connections necessary to launch and grow a particular biopharmaceutical drug. Typically, big pharma just buys or acquires a biopharmaceutical company of interest to them.
Some biopharmaceutical drugs are more profitable than others as well. Biopharmas compose 10 percent of the pharmaceutical market presently, I understand. And with the government health care programs being the largest U.S. payers for pharmaceuticals, Medicare pays 80 percent of the cost of biopharmaceuticals. One profitable biopharma class is known as EPOs, with names like Procrit and Epogen, and are for anemia that is experienced in patients on dialysis or who have cancer in particular. Doctors are monetarily incentivized to exceed dosing requirements of these agents, but this causes premature deaths and accelerated cancer progression for the patients that are over-dosed in this way. Once this tactic was exposed, there are now limitations regarding the amounts used of these EPOs. They are hormone biopharmaceutical drugs, which is one of several classes of biopharmaceuticals.
While biopharmaceuticals are very efficacious and safe, as well as having therapeutic and diagnostic benefits for the very sick, the cost of them is outrageous. Genzyme has one biopharma that costs a half a billion dollars a year. Yet most biopharmaceuticals cost around 100 grand a year for therapy that provides limited life extension of only a few months. Furthermore, with cancer drugs, they are used with chemotherapy, so there is no real improvement in the quality of life of some patients on biopharmaceuticals, considering the devastating side effects of chemo treatmet. Co-pays financially drain such patients and their families, yet there is no other choice for therapy because of the avoidance in the creation of biosimiliars. Oncology, by the way, is the primary commercial focus of biopharmaceutical companies, so maybe competition will be a cost advantage to such patients.
How do these drugs differ from typical drugs that have been made before this advent? Unlike the small molecule, synthetic, carbon based pharmaceuticals of yesterday, biopharmaceuticals, classified under what is called Red biotechnology due to this being a medical process in the biotechnology world, are larger and very complex modified proteins derived from living biological materials that vary depending on what is manufactured and for what disease state. In fact, it is difficult to identify the clinically active component of a biopharma drug. A transformed host cell is developed to synthesize this protein that is altered and then inserted into a selected cell line. The master cell banks, like fingerprints are each unique and cannot be entirely duplicated, which is why there are no generic biopharmas, yet biosimilar drugs are possible, yet not available yet. After this insertion, the molecules are then cultured to produce the desired protein. These proteins are very complex and are manufactured from living organisms and material chosen for whatever biopharma may be desired to be created. It is difficult to identify the clinically active component of biopharma drugs. So manufacturing biopharmas is a difficult process, and a small manufacturing change could and has raised safety issues of a particular biopharma. It takes about 5 years to manufacture a biopharmaceutical. And each class has a different method of production and alteration of life forms to create what the company intends to develop.
Another difference is that biopharmas are regulated under what is called the Public Health Service Act, and unlike the FDA, they authorize the marketing of biopharmaceuticals. The Act’s role in monitoring the promotion of biopharmaceuticals is unknown. Safety protocols are a mystery to me as well.
Presently, there are about 200 biopharmaceutical companies, with maybe a little over 10 percent of them are actually profitable presently. The cost of developing a biopharmaceutical exceeds a billion dollars, with about a third actually making it to market. The market size of biopharmaceuticals is rapidly approaching 100 billion dollars a year, with average annual growth between 10 and 20 percent. Between 20 and 30 biopharmaceuticals make over a billion dollars a year presently. As cancer is the disease focus of biopharma companies, between70and 80 percent of cancer drugs are prescribed off-label.
Regardless of the challenges that are and will be faced by biopharmaceuticals, I’m pleased to see the results of true innovation in pharmacology, and I believe others should behave in a similar manner.
“The progressive development of man is vitally dependent on invention.” — N. Tesla
Dan Abshear (what has been written is based upon information and belief)
John Lawrence
I’d like to offer corrections to some comments by Dan Abshear. For one, physicians are not monetarily incentivised to “exceed dosing requirements” for ESAs (erythropoiesis stimulating agents or EPOs). Physicians have been provided with incentive to use one product over a competitor product through the use of rebates (a business tool that used by many industries, e.g. automakers).
Moreover, there is little evidence to support the notion that physicians in private practice over-prescribed ESAs. Retroactive analysis of claims data shows that the average chemotherapy-induced anemia (CIA) patient receiving ESAs was given drug to maintain their hemoglobin levels at less than the 13 g/dL limit initially provided within the FDA label. Instead, most patients were maintained at between 11-12 g/dL. Data suggesting adverse impact on survival from the use of ESAs comes from clinical trials where ESA dosing rules, often exceeding that with the FDA-approved label, were imposed per protocol in experimental settings. As a result of such data, a new limit of 12 d/dL as a target for hemoglobin in CIA patients has been written into the updated FDA label. Reimbursement by CMS has further limited the hemoglobin target for CIA patients for Medicare/Medicaid patients to a value of 10 g/dL. These recent changes are due to concern over a potential survival impact seen in 8 of the 59 recently reviewed prospective, randomized clinical trials investigating the use of ESAs in support of CIA.
Finally, ESAs are not hormones. ESAs are the result of recombinant human (rhu)protein technology, such that rhuEPO (recombinant human erythropoietin, or EPOGEN/Procrit) is actually a biologic analogue to endogenous human erythropoietin. These recombinant proteins activate cell membrane-bound protein receptors to generate the production of human red blood cells in the same manner as endogenous protein. Hormones are steroidal and typically have nuclear binding sites.
JL