The future of Roche Diagnostics’ AmpliChip product line remains unclear six months after the company bowed to US Food and Drug Administration pressure and decided not to sell the CYP450 drug-metabolism test as an analyte-specific reagent in the United States.
Moreover, the decision by the world’s largest diagnostics company to bypass the ASR route and instead develop and submit the product for regulatory clearance as an in vitro diagnostic in the United States and the European Union leaves in limbo the fate of five additional AmpliChip products Roche was hoping to launch over the next six months.
Fresh doubt surfaced after Roche, in a seven-page, 3,700-word statement earlier this month outlining impending product releases, mentioned the AmpliChip product just twice — a significant omission considering that this product has been a key piece of the company’s molecular diagnostics strategy. (In the first case, the AmpliChip was listed as a “program in development;” in the second case, readers were informed that ‘AmpliChip’ is a trademark.)
Though many companies are currently developing ASRs for drug-metabolism indications, the disposition of Roche’s AmpliChip line and related products is of particular interest to pharmacogenomics researchers because Roche Diagnostics is the biggest molecular diagnostics company in the world.
Last May, one month before the CYP450 chip was to launch, Roche Diagnostics head Heino von Prondzynski said the company would introduce six new diagnostic products over the ensuing 18 months based on Affy’s GeneChip platform [see 5/16/2003 PGx Reporter]. According to that timeline, Roche has until the end of November to release the five remaining products.
Roche was hoping the P450 chip would give it sufficient momentum in the marketplace to launch the products — for human papilloma virus, cystic fibrosis, colorectal cancer, HIV, and leukemia. Also, the company’s plan to release these tests as ASRs would have helped to build a ready-made customer base in time for their debut as IVDs soon there after.
The AmpliChip became ballast instead, and Roche’s intention to launch the new tests remains in doubt. Since Steven Gutman, director of the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, which oversees ASRs, sent his letter on Oct. 29, 2003, to Heinrich Dreismann, general manager of Roche Molecular Diagnostics, Roche has been uncharacteristically quiet about the AmpliChip product line [see 11/6/2003 PGx Reporter].
Roche’s original plan was initially to sell the AmpliChip as an ASR, and then to submit the product for FDA clearance as an IVD in late 2004. Soon after the FDA sent its letter, a Roche spokeswoman said the company still expects to file the AmpliChip as an IVD in the United States and European Union later this year. The company has been selling the P450 chip to drug makers for pre-clinical research since pulling it off the market as an ASR in the US.
A person close to Roche Diagnostics said the company’s “initial projections [to launch six AmpliChip products] have changed significantly” in favor of many high-profile products projected to launch over the next three years and beyond.
In an e-mail response to written questions, Greg Heath, head of clinical genomics and oncology at Roche Diagnostics, said that “during the course of the year, the company evaluated ... [the five remaining AmpliChips] and timelines in light of many factors (including technical feasibility, appropriateness for chip vs. other Roche platforms, and so on).
“As a result, we now have revised expected product lists and timelines for the AmpliChip platform and, in some cases, have proposed different timelines or technology platforms for products in some of the therapeutic areas ... and are engaging in early development work” for other clinical areas. He did not offer specifics, Health explained.
However, according to a slide presented during Roche’s R&D Day earlier this month, Roche is in the early stages of developing microarray-based diagnostics for breast cancer classification, osteoporosis, leukemia, and the early detection and classification of prostate cancer.
“Since many of these tests are in early development stages, it would be inappropriate to speculate on launch or file dates,” Heath wrote.
Though few specifics have been disclosed, the reasons for this strategic shift is not likely financial. The company’s size, and the amount it spends each year on R&D, may make it easier to develop additional AmpliChips as IVDs .
It takes around three years and costs at least $750,000 to file a single IVD for pre-market approval — the AmpliChip’s most likely route to market — according to Gus Rosania, an assistant professor of pharmaceutical sciences at the University of California, Berkeley, who has written about ASRs and IVDs.
Roche appears able to absorb these costs. The Swiss diagnostics titan spent $437 million, or 9.3 percent of total sales, on R&D in 2003 — nearly twice what the next-biggest spender, Abbott Diagnostics, had invested.
Roche’s Short-Term Pipeline
In the seven-page statement released to investors and customers May 5, the company said it plans to release several new therapy-prediction and risk-assessment products between the end of 2004 and 2006, and expects to file all of them for IVD clearance:
- The company late next year plans to launch an undisclosed number of leukemia-stratification products based on its Light Cycler real-time PCR platform, according to a Roche spokesperson. This person said that for this indication, “there are a couple of chromosomal translocations” that indicate whether a particular leukemia will respond to certain therapies. Roche also plans to launch a leukemia product based on the GeneChip, but offered no additional details. The spokesperson said this product will be released “in the long term.”
- Next year, Roche plans to release an AmpliChip p53 product, which is a solid-tumor marker that looks for the p53 tumor-suppressor gene. “We’re in the process of developing this product right now,” the spokesperson said.
“If you know that a drug is dependent on having a functional p53 protein, and you know [a patient] lacks that enzyme activity … you would know that they wouldn’t be the best candidate” for that drug,” the spokesperson said.
- Roche also plans to release two new products based on the company’s Linear Array technology: A cystic fibrosis diagnostic, called Linear Array CF Gold, which comprises mutations common to the United States, where a version of the test is currently sold; and a product is for hemoglobinopathy, which is a group of rare, inherited disorders caused by an abnormally structured hemoglobin molecule. These disorders include sickle cell anemia and various types of thalassemia, according to Medline Plus, an on-line resource for physicians.
- For cardiovascular indications, Roche “hopes in late 2004” to launch tests in Europe for Factor II and Factor V Leiden. These tests, which can help physicians identify individuals at risk for deep-vein thrombosis, have already been cleared by the FDA.
- Finally, the company hopes to release a TaqMan-based assay for bone fractures associated with osteoporosis. The first product, which will comprise a panel for the COL1A1 gene, will debut sometime in 2005, according to the company’s R&D Day presentation.
Roche will also “look longer term at developing an expanded an expanded panel and consider that … for the AmpliChip technology.” This product will likely appear sometime in 2008.