When Charles Bishop, CEO of Opko Health Renal, first started working on a new therapy for treatment of secondary hyperparathyroidism (SHPT) in 2006, the standard of care was insufficient to meet the medical needs of patients with the disease.
In SHPT patients, kidney dysfunction leads to profound vitamin D insufficiency, triggering a range of pathologies that significantly increase the morbidity and mortality associated with chronic kidney disease (CKD). Roughly 20 million people who have stage 4 CKD, and many of those will be at risk of SHPT.
“Ten years later, it’s still pretty much the same situation for patients with SHPT,” explained Bishop. “Physicians counsel their patients on nutritional strategies to increase vitamin D and reduce phosphorous, and when that proves insufficient, they prescribe some type of calcitriol—but it doesn’t solve the root of the problem.”
Shifting the treatment paradigm
One of the challenges of treating SHPT is initiating treatment at the right time. According to Bishop, this will require a complete paradigm shift in the approach to treatment.
CKD is a five-stage disease. By stage four, patients are using phosphorous binders along with various types of injectable calcitriol and by stage five they are on dialysis.
Currently available drugs to treat SHPT are designed for patients with late-stage CKD. One such popular treatment option is Amgen’s blockbuster drug, Sensipar (cinacalet), which is indicated for treatment of SHPT in CKD patients with dialysis.
But Opko wants to meet patient need earlier on in the process. “Our goal is to treat SHPT at its onset, to correct VD deficiency early and prevent SHPT and all of the associated downstream problems that come with it,” said Bishop.
Opko Health has already submitted its investigational SHPT therapy, Rayaldee (calcifediol), for approval by the Food and Drug Administration. The drug is an oral vitamin D prohormone in a modified release capsule.
The main differentiator with Rayaldee compared to other treatment options is the ability to treat SHPT early on. Sensipar, for example, is contraindicated in patients with early-stage CKD.
Early intervention is critical, according to Bishop, because CKD patients with pathologic VD insufficiency become osteoporotic and fracture-prone as their disease progresses.
However, Bishop said that something even more “insidious” can occur. “The excess calcium in the blood is deposited in the vascular system, leading to arterial calcification,” he said.
The link between cardiovascular disease and CKD is widely recognized. According to statistics from the Centers for Disease Control and Prevention (CDC), people with CKD are 16 to 40 times more likely to die from cardiovascular disease than reach end-stage renal dialysis.
The ability to treat SHPT before stage 4 could be a major game-changer. As Bishop explained, “There are no other prescription drugs available or in development that address the underlying cause of SHPT.”
The FDA is expected to decide on approval on or before October 22.
Miami-based Opko has a well-established diagnostics portfolio with an international presence, but this is its first drug candidate. Last week, Opko announced a co-development and commercialization partnership with Vifor Fresenius Medical Care Renal Pharma for Rayaldee. Vifor Pharma has significant reach and penetration in the global CKD market, giving Opko a complementary partner.
Under the terms of the deal, Vifor Pharma has exclusive rights to market Rayaldee in Europe, Canada, Mexico, Australia, and South Korea. Opko has retained all rights in the US, Latin America, Russia, China, Taiwan, and Japan.
In exchange, Vifor paid Opko $50 million up front, with potential for an additional $232 million in regulatory and commercial milestone payments.
“Vifor Fresenius is very respected in renal care,” said Steve Rubin, an executive vice president at Opko Administration.
“In addition to their well-established distribution network, our partner will be able to take the data that we have to support the NDA for Rayaldee and submit it to the European Medicines Agency (EMA). Our expectation is that no additional clinical studies will be needed.”
Overcoming manufacturing setbacks
It has not all been smooth sailing for Opko on the regulatory front, however. Opko first submitted application for Rayaldee last year, but it was surprised when it was hit with a complete response letter from the FDA in late March.
The letter stemmed from manufacturing issues at a Florida plant of Catalent, the contract research organization Opko had hired.
“The FDA discovered a problem during a routine inspection of our third-party manufacturer, a well-respected CRO, but it was quickly resolved. The CRL did not cite any safety, efficacy or labeling issues associated with Rayaldee, and they did not ask us for any additional studies,” Rubin said.
“We recovered quickly and the FDA accepted our resubmitted NDA on April 22, 2016.”
While the issues were apparently not tied to Rayaldee, the deficiencies at the Catalent plant set back Opko’s plans by six months.
Opko plans to deploy a small specialty sales force with 25 reps for a U.S. launch if Rayaldee wins approval. Eventually, however, Rubin expects that this will be expanded to 75 dedicated reps providing national coverage.
“We are waiting to hire the sales team until we get through the last regulatory steps, so we can save money,” Rubin explained.
The reps will have a challenging task. They will need to convince their prime targets—ephrologists and endocrinologists—to rethink their approach to treating patients with CKD.
“We have to raise awareness about a new way of addressing SHPT before it becomes a problem. A large part of our marketing strategy is focused on education and the need to help HCP’s and payers understand Rayaldee’s MOA,” Bishop explained.
“Once payers understand the implications of treating SHPT before it starts in CKD patients, it should not be a challenge getting coverage.”
Amgen, Shire competition
Opko Health estimates the SHPT market is worth $12 billion. But it will have competition to capture that value.
Revenues from Amgen’s Sensipar jumped 22% to $1.41 billion last year, and the company is in late-stage development of AMG416, a successor drug. The new compound is expected to be a major competitor in this space, particularly as Sensipar loses patent exclusivity.
Additionally, in January 2015, the FDA approved NPS Pharma’s Natpara for treatment of hypocalcemia secondary to SHPT in CKD patients.
NPS was subsequently acquired by Shire and Natpara has earned $15.6 million in sales through the first quarter this year, indicating annual growth over its 2015 revenue of $24 million.
The six months lost to the manufacturing violations at the Catalent plant could prove costly for Opko as it seeks to enter this competitive market. But by aiming to treat patients early in the disease progression, Opko might skip ahead of its rivals too.