Amgen Looks To Build On Blincyto Momentum As It Enters A Year Loaded With Milestones

Three 2015 filings play a key role in the big biotech offsetting expected revenue declines for four legacy products. The biggest test will be the showdown between its PCSK9 inhibitor evolocumab and Sanofi/Regeneron’s competing alirocumab, which is expected to reach market first.

With a new cardiovascular commercial team in place and expecting three new drug approvals in 2015, two of them in CV indications, Amgen Inc. talked up its near-term future during a Jan. 27 investor call, contending that several late-stage candidates will offset expected revenue losses for its legacy products.

On the big biotech’s fourth quarter and full year 2014 earnings call, CEO Robert Bradway pointed to December’s early approval of Blincyto (blinatumomab) in acute lymphoblastic leukemia as well as a new on-body injector device for neutropenia drug Neulasta (pegfilgrastim) as auguring a wave of new products that will bolster Amgen’s top and bottom lines (Also see "Amgen’s Breakthrough Blincyto Clears FDA At Breakneck Pace, But With REMS Attached" - Pink Sheet, 3 Dec, 2014.).

Blincyto, approved in just 2.5 months, represents Amgen’s successful entry into the heated cancer immunotherapy space, and the first product out of its BiTE bispecific antibody platform. The new delivery system could help to extend the commercial life of Neulasta, the Neupogen (filgrastim) follow-on whose patent protection expires this year (Also see "Amgen To Defend Neulasta Against Biosimilars With New Delivery System" - Pink Sheet, 3 Nov, 2014.).

Neupogen will face biosimilar competition soon. Apotex Inc. filed a biosimilar version of pegfilgrastim for FDA approval in December; Novartis AG’s generics unit Sandoz Inc. filed for a biosimilar (Zarxio) of the same drug in May 2014 (Also see "Apotex Biosimilar Goes To FDA, But May Enter Crowded Market" - Pink Sheet, 18 Dec, 2014.). Hospira Inc. also filed a biosimilar of Neupogen (and also Johnson & Johnson’s Procrit) for FDA review in mid-December (Also see "Will Hospira’s Epogen Biosimilar Follow Sandoz’s Filgrastim Playbook?" - Pink Sheet, 12 Jan, 2015.).

A significant portion of the Jan. 27 call was given to discussing Amgen’s dual role as a biologics innovator that also is seeking to bring biosimilar versions of other company’s drugs to market, with Bradway asserting that that duality gives the biotech an edge with regulators (Also see "Amgen Cites Strength From Being Both Innovator And Developer In Biosimilars Space" - Pink Sheet, 28 Jan, 2015.). Amgen plans to bring five biosimilars to market between 2017 and 2019 and has nine clinical candidates in its biosimilars pipeline, including AbbVie Inc.’s Humira (adalimumab), Roche’s Herceptin (trastuzumab), Avastin (bevacizumab) and Rituxan (rituximab) and J&J’s Remicade (infliximab) (Also see "Amgen “Doubling Down” On Innovation As It Sets A Course For The Future" - Pink Sheet, 3 Nov, 2014.).

“We’ve said for some time we thought there was benefit for both our innovative products and our new potential biosimilar products that we participate in both aspects of the market,” Bradway said. “Through time, what we have found is we continue to learn about our own innovative process development efforts, etc., by the virtue of the work we’re doing in our biosimilars program. I think our dialogue with the regulators around the world is enhanced by the fact we are recognized to be both an innovator and a company that is seeking to advance biosimilar molecules, so we’re continuing to work both sides of this.”

Another Watershed Year In 2015?

But greater earnings potential is offered by Amgen’s new molecular entity candidates, including the PCSK9 cholesterol therapy Repatha (evolocumab), heart failure drug Corlanor (ivabradine) and metastatic myeloma candidate talimogene laherparepvec (T-VEC), all of which are being reviewed at FDA or will be filed imminently. Bradway called 2014 a “watershed year” for Amgen in drug development and predicted 2015 would be more of the same, thanks to those candidates, as well as a label-expansion filing for Kyprolis (carfilzomib) and expected NDAs for brodalumab in psoriasis and AMG 416 for secondary hyperparathyroidism.

Analysts seem less convinced that this late-stage pipeline will suffice to cover the expected losses from patent expirations and new competition to Epogen, Neulasta, Aranesp (darbepoetin alfa) and Enbrel (etanercept). In a Jan. 28 note, BMO Capital Markets analyst Jim Birchenough rated the company “market perform” and said its current valuation “underestimates challenges to its legacy products and overestimates the growth potential from its next product wave.”

More optimistic is Morningstar’s Karen Andersen, although she noted the challenges Amgen will face positioning Repatha as likely the second-to-market PCSK9 inhibitor, behind Sanofi/Regeneron Pharmaceuticals Inc.’s Praluent (alirocumab), which, thanks to a priority review voucher, is on path to be approved at least a month before Repatha (Also see "Formulary Focus: PCSK9 Drug Prices May Lead Payers To Impose Coverage Restrictions" - Pink Sheet, 26 Jan, 2015.).

“Despite discussion of potential pricing pressure in this market – which we believe is a real threat, given the similarity of Regeneron/Sanofi’s own PCSK9 antibody Praluent and the similar launch timelines – we think there is plenty of room for the PCSK9 market to achieve $10 billion in peak sales, based on the sheer number of patients who would benefit from this chronic treatment,” Andersen wrote in a Jan. 28 note. She projects peak annual sales of $4 billion for Repatha. Payers are already discussing coverage restrictions for the class (Also see "Formulary Focus: PCSK9 Drug Prices May Lead Payers To Impose Coverage Restrictions" - Pink Sheet, 26 Jan, 2015.).

Exec VP-R&D Sean Harper told the investor call that while it’s too soon to talk rebating or contracting strategy, Amgen will be pricing based on evolocumab’s “unique and definitive value proposition,” adding that “obviously rebating contracts are essential to get a preferred position on the formulary.”

Harper said Amgen has completed enrollment of a coronary intravascular ultrasound trial for evolocumab, while it continued to enroll its outcomes study on an accelerated pace. Amgen had been expecting to have data from its cardiovascular outcomes trial in 2018, but revealed during an Oct. 28 investor meeting that it has increased the number of patients in the study by 5,000 to reach more events faster and to get the data sooner. Now, it expects to have cardiovascular outcomes data in hand by the end of 2017 (Also see "Amgen On PCSK9 Inhibitor Evolocumab: “We Are Ready To Go”" - Pink Sheet, 28 Oct, 2014.).

The biotech is working closely with regulators on its various planned evolocumab filings, he said, and will present new data analyses from its clinical trial program at the American College of Cardiology scientific sessions in San Diego this March. Harper sidestepped a question about whether FDA would hold an advisory committee review for evolocumab or Corlanor, saying that the general default is to have meetings for drugs with new mechanisms.

In addition to building a commercial infrastructure, both PCSK9 sponsors are preparing for launch through educational and outreach efforts (Also see "Educational Efforts Are First Front Of Marketing Battle For PCSK9s" - Pink Sheet, 8 Dec, 2014.). On Jan. 29, Amgen announced an agreement with the Familial Hypercholesterolemia Foundation and Stanford University School of Medicine to build awareness and bolster diagnosis of the rare genetic high cholesterol disorder; the FIND FH initiative will help identify appropriate candidates for therapy with PCSK9 inhibitors.

Approval Delays For Two Candidates

In addition to evolocumab, Amgen has T-VEC and Corlanor also under review at FDA, but those are both facing delays due to the agency’s need for more data, Harper explained (Also see "Amgen Amps Up T-VEC Story At ASCO With Filing Plans And Combos" - Pink Sheet, 5 Jun, 2014.). Each filing recently received a three-month extension of its action date, he noted.

“In the case of T-VEC, the agency requested additional manufacturing data for this very unique product which may require additional review time,” the exec said. The oncolytic virus, an engineered version of the herpes simplex-1 virus that should both kill cancer cells and stimulate an immune system response, harkens to an older version of vaccine-type immunotherapy that largely has been eclipsed by the immune checkpoint inhibitors, which are significantly easier to produce.

“In the case of Corlanor, the agency requested more of the existing clinical data [that] were originally agreed to for our heart failure specific submission, also potentially requiring the additional review time,” Harper said. “We provided the data for both programs as requested and we continue to work productively with regulators to bring these innovative medicines to the patients that need them as soon as possible.”

Amgen acquired U.S. commercial rights to ivabradine from Servier SA in 2013 and the NDA for chronic heart failure has been granted a priority review, positioning it for potential approval during 2015 (Also see "Amgen Positions Ivabradine As A Foot In The Door Ahead Of PCSK9 Launch" - Pink Sheet, 20 Nov, 2013.). The company expects the launch of ivabradine will help pave the way for evolocumab.

The firm also announced the filing of an sNDA Jan. 27 for Kyprolis in patients with relapsed multiple myeloma who have received at least one prior therapy, a potential label addition Amgen and its subsidiary Onyx think would greatly expand the appropriate patient base for the proteasome inhibitor.

The company also is expecting to file its psoriasis agent brodalumab in 2015, and potentially its treatment for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, AMG 416. It expects Phase III head-to-head data for the investigational I.V. calcimimetic against its older Sensipar (cinacalcet) in the first half of the year.

With brodalumab, Amgen and development partner AstraZeneca PLC will be playing catch up to Novartis’ recently approved first-in-class interleukin-17 inhibitor Cosentyx (secukinumab) (Also see "Novartis Gets First-Mover Advantage With FDA Approval Of Cosentyx For Psoriasis" - Pink Sheet, 21 Jan, 2015.).

“I think that the data that we generated with brodalumab, [which] will be included in our filing, both head-to-head through Stelara and in placebo-controlled trials, have generated the best skin-clearance data that has existed for any agent that has been tested in [psoriasis],” Harper asserted. “That said, we don’t obviously have head-to-head data against the other IL-17 molecules. But I think that the general impression that the experts in the field that look at the datasets have, is that the efficacy of brodalumab is unmatched in the class so far with the data that’s been generated. So I think that’s probably the key kind of differentiating.”

He also pointed out that brodalumab is a receptor-blocking antibody rather than targeting the ligand, “so it is possible one would see differences in efficacy.” The proof will be in labeling, the exec noted.

In terms of advancing its pipeline, Amgen will start a Phase III program for its migraine therapy AMG 334 and generate Phase III readouts from two of its biosimilar programs by the end of the year.

AMG 334, a CGRP receptor antibody, “performed very nicely” in a Phase IIb dose-ranging study in patients with episodic migraines, Harper said, “resulting in our decision to move aggressively into Phase III.” A Phase IIb dose-ranging study in chronic migraine is fully enrolled, he added, and the firm expects that the mechanism of blocking the receptor rather than the ligand will translate to a more favorable dosing schedule, so “AMG 334 has a clear potential to be a best-in-class agent for migraine prophylaxis.”

Amgen will be deciding whether to advance the oral formulation of omecamtiv mecarbil (AMG 423) into Phase III this year, as it reviews Phase IIb data with Cytokinetics Inc.

In terms of immuno-oncology, Amgen has initiated a combination metastatic melanoma study of T-VEC with Merck & Co. Inc.’s PD-1 inhibitor Keytruda (pembrolizumab) “and are in the planning stage for additional such combination checkpoint inhibitor studies in other tumor types,” Harper said. The firm already has a trial running testing T-VEC with Bristol-Myers Squibb Co.’s Yervoy (ipilimumab) in unresected melanoma.

The firm has groundwork to build its cancer immunotherapy portfolio on key platforms, including the existing BiTE and oncolytic virus capabilities as well as a new collaboration with Kite Pharma Inc. on CAR-T technology (Also see "Marriage Of Kite’s CAR-T Platform To Amgen Targets Will Expand Pipeline For Both" - Pink Sheet, 5 Jan, 2015.).

Morningstar’s Andersen sees signs of encouraging longer-term earning power in Amgen’s advancements in immuno-oncology, exemplified by the Blincyto approval and the CAR-T deal. The firm has captured the lead with bispecific antibody engineering, so while Amgen may not be an active player in the immune checkpoint inhibitor space, it still could prove to be a cancer immunotherapy powerhouse.