In a unanimous vote on Monday, the Endocrinologic andMetabolic Drugs Advisory Committee of the FDA recommendedapproval of Genentech Inc.'s Nutropin human growth hormonefor treating short stature associated with chronic renalinsufficiency (CRI) in children.
The eight-member FDA panel recommended that Nutropin beapproved for use by the 3,000 or so children with CRI until thetime of renal transplantation. Nutropin has been designated anorphan drug for this indication, for which there is currently noavailable treatment.
If FDA approves the drug, Genentech (NYSE:GNE) of South SanFrancisco, Calif., will have an approved growth hormone poisedto enter the market when Eli Lilly and Co.'s growth hormone,Humatrope, loses its orphan drug exclusivity.
Results of ongoing Phase III clinical trials on 195 patientsshowed that Nutropin administered prior to renaltransplantation significantly increased the rate of growth andthe height gain of children with CRI prior to renaltransplantation. These were the main endpoints for clinicalefficacy, and for both there was a "highly statisticallysignificant difference between treatment with Nutropin andwith placebo," explained FDA committee member DonMarticello.
Patients received 0.05 milligrams per kilogram of Nutropinsubcutaneously daily for the duration of the trials. (Thedouble-blinded, placebo-controlled safety and efficacy triallasted 24 months; the open-label trial lasted three years.) Andalthough the studies weren't designed to assess post-transplantation growth, the data suggested that patientsmaintain the height gains they achieved while receiving thegrowth hormone.
"We provided enough data to convince the committee that theheight gained in the two-year controlled study is maintainedinto adulthood," said Edward Kohaut, professor of pediatricsand director of nephrology at the University of Alabama,Birmingham, and one of the principal clinical investigators.
The safety profile for Nutropin was roughly the same as thatalready established for Genentech's Protropin growth hormone,which is used for treating growth hormone inadequacy.Nutropin therapy did not affect the progression of renaldisease.
The FDA advisory committee attached several caveats to itsrecommendation, however. First, Genentech must conductPhase IV (after-market) studies to assess the effects of long-term (beyond two to three years) administration ofrecombinant human growth hormone in the patient population.In fact, Genentech already has plans to add the renal patientsto an existing registry of about 16,000 people treated withgrowth hormone (Protropin), the National Cooperative GrowthStudy.
The panel also recommended that the package insert clearlystate that the growth hormone is not indicated for use in post-renal transplant patients who are being givenimmunosuppressive drugs.
The committee members expressed concern that the use of agrowth hormone in immunocompromised individuals mightincrease the likelihood of various malignancies, especiallyleukemia and osteosarcoma. And although there are no datayet on these possibilities, Genentech has so far found noincidence of osteosarcoma among the 16,000 patients alreadybeing followed in extensive post-marketing analyses throughits growth study registry.
Nutropin is Genentech's second recombinant human growthhormone product; it differs from the FDA-approved productProtropin in that it lacks the N-terminal amino acid methionine.Nutropin is identical in amino acid sequence to the naturallyoccurring hormone, a property that makes it equivalent toLilly's FDA-approved human growth hormone, Humatrope.
According to Robert Faulkner, an analyst with S.G. Warburg, themarket for human growth hormone is more than $1 billion inthe U.S. and Europe. Although Genentech's Protropin now hasthe lion's share of U.S. sales (70 percent), Lilly's Humatrope stillcontrols the rest of the market.
However, Humatrope will be relieved of its orphan drug statusnext year, which will open up the playing field to all comerswho have produced human identical forms of growth hormone,including Novo Nordisk, Ares Serono and Bio-TechnologyGeneral Corp. But with Genentech now having an FDA-approvable version of its own, it could be poised to capture therest of the market, according to Faulkner.
Although Faulkner foresees Nutropin bringing in roughly $55million in sales for treating chronic renal insufficiency andTurner's syndrome (a genetic deficiency in boys), he alsoforecast that "Nutropin could easily replace Protropin andprobably will for off-label indications after Lilly's orphan drugstatus expires."
"We think this is a marketing issue," said Faulkner. This(recommendation for approval) gives Genentech as muchadvantage as one could possibly get in this market."
Genentech's stock was up 38 cents a share on Monday, closingat $46.75.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.