Two biologics in Amgen Inc.’s late-stage pipeline could have utility in broad primary care markets: high cholesterol and osteoporosis.

Each addresses potentially lucrative commercial opportunities. However, Amgen – a big biotech that has built its business playing in specialty fields like kidney disease, autoimmune disease and cancer – will need to execute carefully if it is to extend its success to primary care, where new high-priced injectable drugs face off against low-cost oral generics.

For Amgen, in the midst of a transition, the time may be right to extend further into broad markets where the potential for a big return is helping to lure investors. The company has already dipped its toe into primary care with the 2010 launch of Prolia (denosumab), a twice-yearly injection for osteoporosis, but it hasn’t distinguished itself there.

With its workhorse anemia drugs Aranesp and Epogen under pressure from changing treatment practices and government cost reductions policies, and its blockbuster neutropenia franchise Neulasta/Neupogen and its rheumatoid arthritis brand Enbrel maturing, Amgen is focused on building sales of denosumab and following up with new drugs that can straddle the specialty and primary care line.

Amgen’s management team – also transformed in the past year – talked about the company’s progression into primary care as part of its long-term growth strategy during an investor meeting in New York Feb. 7. The meeting was the first business overview for Amgen’s new CEO Robert Bradway, who succeeded Kevin Sharer as CEO in May 2012, as well as for Bradway’s right and left hands, exec VP R&D Sean Harper, who replaced longtime R&D head Roger Perlmutter in February 2012, and Exec VP-Global Commercial Operations Tony Hooper, who joined the company from Bristol-Myers Squibb Co. in October 2011.

The two key drugs with potential in primary care are AMG 145, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of low density lipoprotein cholesterol (LDL-C), and romosozumab (AMG 785), a sclerostin inhibitor for the treatment of postmenopausal osteoporosis. Both are being tested in large Phase III trials. If the Phase III tests turn out positively and the drugs reach the market, Amgen hopes to leverage its experience with Prolia to make the drugs a commercial success.

“We are the first company to have entered a biologic primary care market with Prolia, and we have learned a lot in the last 18 months and we’re applying those learnings as we go forward,” said Hooper during the meeting.

Hooper wasn’t explicit about what Amgen has learned, but analysts generally have criticized the company for poorly educating primary care physicians on navigating the reimbursement process, namely the prior authorization usually required for Prolia, and on the benefits of an injectable in what has been an oral, small molecule space. Consensus is that the company did not put enough muscle behind the launch because they were so focused on its applications in oncology.

For PCSK9, Cardiologists First

AMG 145 in particular is attracting a lot of attention as PCSK9 inhibitors have shown promise across the industry as a new class of drugs to treat high cholesterol, potentially on top of widely used statins. Amgen, along with rival Sanofi/Regeneron Pharmaceuticals Inc., have the most advanced compounds; Amgen released positive Phase II data in November showing strong LDL-C lowering following treatment with AMG 145 Also see "Momentum Builds For PCSK9 Class, But Proof Of Safety Still Thin" - Pink Sheet, 12 November, 2012.. The race is tight, though: the Sanofi/Regeneron compound, alirocumab, recently entered Phase III, with a preliminary data read-out in the third quarter of 2013, and full data release expected in 2014.

Amgen has also initiated its Phase III program for AMG 745, which includes seven clinical trials enrolling more than 26,000 patients. Data from four studies are expected in 2014: in patients at risk for cardiovascular disease who are on statin therapy, in patients who cannot tolerate statins, as monotherapy and in patients with the genetic rare disease heterozygous familial hypercholesterolemia. A larger outcomes study is expected to read out in 2018. Amgen expects the drug would initially be improved for a smaller specialty indication in high-risk patients and potentially expand into a broader primary care market later.

“We expect at least initially the launch of PCSK9 will be in the cardiology field, and we expect to build a specialty effort to reach those physicians directly,” Bradway said in a follow up media briefing. “Over time, it will become more a primary care opportunity for us. As and when the data for PCSK9 warrant this [to be] in the hands of primary care physicians we will look forward to that challenge.”

The Phase III program for romosozumab included two pivotal studies enrolling 10,000 patients, one trial evaluating incidence of vertebral fractures at 12 and 24 months in 6,000 patients versus placebo, and a second study comparing romosozumab versus alendronate (Merck & Co. Inc.’s Fosamax and generics) evaluating incidence of clinical fracture and new vertebral fracture. The product is partnered with UCB Pharma SA. In a Phase II study, treatment with romosozumab resulted in significant gains in bone mineral density compared to open-label comparators (alendronate and teriparatide) and placebo at 12 months.

Following the meeting, the partners announced a decision not to pursue a different indication for romosozumab for accelerated fracture healing. That news came after a Phase II test and regulatory guidance indicating that acceleration of fracture healing was not a viable endpoint for continued study, but the companies said no safety issue arose in the study.

“[Denosumab] will be a $3 billion-plus franchise,” Exec VP-Global Commercial Operations Tony Hooper predicted.

In osteoporosis, Amgen sees the opportunity for synergies with its Prolia marketing effort. The company has a sales team that already calls on the target physicians, and the addition of another drug will yield efficiencies. The drugs potentially could be used together as well. Prolia stops the excessive breakdown of bone, while romosozumab is designed to help build more dense bone mineral. In the placebo-controlled pivotal trial, Amgen is studying romosozumab followed by denosumab.

“We’ve spent quite a bit of time learning around the Prolia experience and making sure we understand what changes the curve, what doesn’t change the curve, where we get to patients,” Hooper said. “Clearly, when I look at the access environment in a situation like that, when I look at the patient journey and the power of the patient talking to a physician, it’s no longer a game of feet on the street. It’s truly understanding a different model that we need to bring to bear.”

Getting Prolia Up And Running

The launch of Prolia got off to a slow start, but more recently there are signs it may finally be hitting its stride. The drug generated $203 million in 2011, its first full year on the market, but its sales more than doubled in 2012, reaching $472 million. Amgen’s inexperience in primary care could be to blame for the slow start, especially since the drug faced a hard marketing proposition as a premium-priced injectable – the most expensive drug in the therapeutic area – in a highly genericized market Also see "Prolia Pricing: Straddling Osteoporosis And Oncology" - Pink Sheet, 7 June, 2010..

But Amgen also never fully appreciated the osteoporosis opportunity. The company viewed an indication in osteoporosis as the fastest way to the market for denosumab, but had bigger expectations for the drug in oncology indications, including reduction of skeletal-related adverse events in cancer patients and especially bone metastases prevention. The drug was approved shortly after in November 2010 for skeletal events and is marketed there as Xgeva, but FDA rejected it for bone metastases prevention Also see "Amgen Obtains Broader Label For Denosumab With Oncology Indication" - Pink Sheet, 22 November, 2010.. Xgeva’s sales have been stronger than Prolia’s; the drug generated $748 million in 2012.

Denosumab has morphed into a valuable drug for Amgen, with sales for both indications topping $1.2 billion in 2012. Hooper said he is convinced that “this will be a $3 billion plus franchise.”

One reason sales of Prolia are improving is market access and work the company has done to improve access, Hooper said, though he didn’t specify how. “We continue to work to make sure we do have unrestricted access, to make sure that the prior authorization process is clearly understood and easily executed by physicians. We have seen a dramatic reduction in the number of insurance rejections, and we’ve seen an increase in the number of revisits by patients.”

In an effort to further improve its primary care execution, the company has increased investment behind Prolia and adjusted its marketing plan. In the second quarter of 2012, the company launched for the first time a direct-to-consumer TV campaign promoting the drug, a step which immediately correlated to increased use. In the fourth quarter, the company increased the size of the sales force, resulting in another spike in use, according to Hooper.

“We launched with about 48% coverage of targets in the U.S., and we’ve now gone to about 65% coverage of all the top targets in the U.S.,” Hooper said.

“The investment we did in the second quarter, we spent time researching that and it’s clearly during that period that Prolia became the most requested PMO brand of product, and 95% of the time the patients request the drug, they’ve received it,” Hooper added.

Despite its effort to expand into primary care, Amgen has lots of activity ongoing in R&D to yield products for specialty indications. Amgen’s pipeline includes a total of eight products in late-stage testing that will generate pivotal data from 2013 to 2016. The company also has six biosimilars in development that it expects to launch starting in 2017 ([A#14130207005]).

On Amgen’s Agenda: Bring Biologics To Primary Care

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