Riquent

Riquent is a mixture of four pieces of double stranded DNAs, each 20 nucleotides in length. The mixture is an analog of the DNA that simulates a B cell-mediated autoimmune response in many lupus patients. In theory, the drug stimulates B cells in lupus patients to become tolerant to stimulation by their own DNA, dampening the autoimmune response. ACR data do little to assuage concerns that Riquent will not be approved in a timely manner. LJPC plans to submit an NDA for Riquent in “December 2003 or January 2004.”

In the absence of a more substantive data set, LJPC plans to argue that clinically and statistically significant health-related quality of life (HRQOL) improvements observed in the trial program warrant U.S. marketing approval of Riquent. Although the 6- and 12-month data derived from a well-validated HRQOL investigational tool have been impressive, it remains uncertain the degree to which substantive outcomes were truly measured prospectively. Therefore, the probability of FDA approval remains below average despite the current regulatory climate favoring palliative medicines that do not necessarily improve primary or clinical investigational goals. A more appealing NDA submission would derive from a successful new trial more clearly demonstrating prospective, placebo-controlled, efficacy across as broad a range of HRQOL or other clinical outcomes.

One ACR poster reviewed phase III Riquent data generated by a 298-lupus patient cohort randomized to receive Riquent or a placebo for up to 22 months. Riquent administration was associated with 25% fewer renal flares and 21% fewer major lupus flares compared with placebo. These potentially clinically significant differences were not statistically significant. Statistically significant reductions in antibodies to double-stranded DNA (dsDNA) were observed. The reasons for the disconnect, given that antibodies to dsDNA are believed to precipitate lupus renal disease, remain unresolved.

A second poster reviewed the phase III and phase II/III Riquent trials demonstrating, to a certain extent, that subjects with sustained reductions in antibodies to dsDNA had a lower incidence of both renal flare and major lupus flare. A third poster confirmed the agent’s reassuring serious adverse event and adverse event profiles.

LJP 1082

LJP 1082 has generated phase I/II data suggesting that LJPC will continue to develop the agent, and/or next-generation analogs, for the management of antibody-mediated thrombosis associated with the antiphospholipid syndrome.

Antiphospholipid syndrome is associated with autoimmune thrombotic difficulties that result in low platelet counts, miscarriages, other adverse obstetrical outcomes, venous thromboembolism, strokes, and heart attacks. Currently, it is managed with standard, often life-long, anticoagulation. Instead of managing the thrombotic complications of antiphopholipid syndrome, LJPC hopes to inactivate the B cells that cause the condition. LJP 1028 inactivates specific B cells that produce anti-cardiolipin antibodies thought to be the primary cause of the antiphospholipid syndrome.

A 20-patient, placebo-controlled investigation randomized participants to receive placebo or doses of LJP 1082 ranging from 1 to 200 mg. Safety and adversity differences were not observed between groups. Moreover, circulating antibodies from treated patients bound to LJP 1082 in a dose-dependent fashion. The overall clinical and biochemical data set support advancement of the program.