Hepatitis C viral loads dropped to undetectable levels in all patients receiving for about a month an investigational drug from Vertex Pharmaceuticals Inc.
More specifically, the dozen treatment-na ve patients receiving the small-molecule, protease inhibitor VX-950 had plasma hepatitis C virus RNA levels lower than 10 IU/mL after 28 days of treatment. Those results, in the estimation of ThinkEquity Partners LLC analyst Andrew McDonald, were "astounding" and "phenomenal."
For Vertex, of Cambridge, Mass., the latest findings are not only exciting but also, importantly, in line with past data.
"These results are very consistent with other results that we've already presented," said Zachry Barber, a media relations specialist for Vertex, adding that the antiviral activity is in harmony "across the board" with two other trials.
The 28-day study is the third in a series designed to guide the design of larger and longer Phase II studies. The latest trial's 12 patients, who have genotype 1 of the virus, received VX-950 in a 750-mg tablet formulation every eight hours in combination with standard doses of pegylated interferon alfa-2a (Pegasys, from F. Hoffmann-La Roche Ltd.) and ribavirin (Copegus, also from Roche). At the end of 28 days, they completed VX-950 dosing but were required to continue on Pegasys and Copegus.
The study was not designed to evaluate sustained viral responses in patients. There were neither treatment discontinuations nor any serious adverse events, and a detailed safety analysis remains ongoing.
For patients entering the study, the distribution of baseline plasma hepatitis C virus RNA values was typical for a treatment-na ve patient population. At the end of the first week, half of them had virus levels below the 30 IU/mL limit of quantitation, including a pair with undetectable levels below 10 IU/mL. After the second week, plasma hepatitis C virus RNA was below the limit of quantitation in 11 of the 12 and undetectable in three of them. After three weeks, plasma hepatitis C virus RNA was below 30 IU/mL in all of them and undetectable in nine.
As previously mentioned, at the end of four weeks, viral loads were undetectable in all 12 patients. Also, no patients showed evidence of viral breakthrough while on treatment.
There is "a lot of excitement in the HCV community and among investors," Barber said, as a result of the speed of the "dramatic" reduction in hepatitis C virus RNA and its rate of decline seen consistently across three early stage studies.
The two other recently reported studies of VX-950, which the FDA has designated a fast-track product, include Phase Ib data showing that VX-950 and Pegasys produced a 300,000-fold reduction in viral levels after two weeks. An earlier Phase Ib study showed that patients receiving 750 mg of VX-950 as monotherapy achieved a 25,000-fold reduction in viral levels after 14 days of dosing. While such data support further single-agent trials, Vertex's focus going forward is on combination therapy of VX-950 and Pegasys, either with or without Copegus.
The company plans to present the full data set from its latest study at a medical conference later this year.
Vertex also has completed three-month animal toxicology studies of VX-950 that will support clinical studies up to three months long. Such trials are planned to begin following FDA review of the latest results, preclinical and clinical, and the agency's review of a proposed protocol. Vertex will submit that information to the agency this quarter.
Barber declined to detail the potential design of future studies, calling the protocols "to be determined," as FDA input is crucial to the next set of trials. He noted that Vertex's should begin a three-month Phase II study by the end of this year and move the program into pivotal Phase III trials next year.
The analyst McDonald said he believes a three-month treatment duration to be possible.
Vertex has partnered VX-950's Asian rights with Mitsubishi Pharma Corp., of Osaka, Japan, and Barber said there's "a possibility" for partnering the product outside North America, maybe later this year. "We have said all along that we intend to take this forward ourselves, independently, in the U.S.," he added.
The company's other primary internal focus is VX-702, a p38 mitogen-activated protein kinase inhibitor for rheumatoid arthritis. Data from a large Phase II trial are due next quarter. Also, Vertex soon plans to reveal a clinical candidate for cystic fibrosis to move forward under a new collaboration with the Cystic Fibrosis Foundation.
The company's investment in another product for hepatitis C, merimepodib, will be limited following completion of a 315-patient study to assess its use in combination with Pegasys and Copegus.
Vertex's other product with fast-track designation is VX-385, a protease inhibitor for HIV that is being developed with GlaxoSmithKline plc, of London.
Vertex reported fourth-quarter and year-end results Tuesday, posting an unaudited 20-cent loss per share for the quarter ended Dec. 31, beating consensus estimates by 3 cents. It had a $147.1 million loss for the full year on the basis of non-generally accepted accounting principles, or $1.65 per share.
Full-year total revenues increased to $160.9 million, up from $102.7 million the previous year, due to collaborative research and development agreements and an increase in HIV product royalties. As of Dec. 31, the company had about $407.5 million in cash, cash equivalents and available-for-sale securities, and in the coming year, it is projecting a non-GAAP loss to range between $165 million and $185 million.
On Tuesday, Vertex's shares (NASDAQ:VRTX) gained $1.81 to close at $36.11.