Can Pfizer’s Cholesterol Drug Catch Up To The Competition?

Pfizer's (PFE 2.40%) revenue has dramatically declined since 2011, the year Lipitor went off patent in the U.S. The blockbuster cholesterol drug, which already lost exclusivity in several markets at the time, still generated sales of $9.6 billion that year, accounting for 14% of Pfizer's top line.

Between fiscal 2011 and 2013, Pfizer's annual revenue fell 15%. To protect its bottom line, Pfizer sold and spun off businesses, reduced its workforce, and slashed its dividend. But the challenge of replacing Lipitor -- which only generated $1.5 billion in sales in first nine months of 2014 -- remained. Yet Pfizer still has another potential blockbuster cholesterol drug in its pipeline -- bococizumab, one of two drugs (the cancer drug palbociclib is the other) which could get Pfizer's top line growth back on track.

But is the closely watched bococizumab falling too far behind its rivals to matter?

Why bococizumab matters
Lipitor, like many other blockbuster cholesterol drugs, is a statin. Statins target a liver enzyme to inhibit the production of LDL cholesterol, but can stimulate the production of another enzyme known as PCSK9. PCSK9 binds to a liver's LDL receptors, throttling the liver's ability to reduce LDL ("bad") cholesterol levels.

That's why a new class of drugs, known as PCSK9 inhibitors, were developed. These drugs include Pfizer's bococizumab, Sanofi (SNY 2.00%)/Regeneron's (REGN 0.32%) alirocumab, and Amgen's (AMGN 2.35%) evolocumab.

Amgen is currently in the lead. Its biologics license application, or BLA, for evolocumab was accepted by the FDA for review in November, and it hopes that the drug will be approved by next August. Sanofi and Regeneron completed six phase 3 trials for alirocumab earlier this year, but Amgen sued the two companies in October to block their upcoming BLA. Pfizer, which initiated its phase 3 trials for bococizumab earlier this year, is currently in last place.

Leerink Partners estimates that alirocumab and evolocumab could both generate peak sales of $4.3 billion if approved. If bococizumab comes anywhere close to matching those numbers, it could help fill the gaps in Pfizer's top line. But before we call this drug the "next Lipitor", we should remember that PCSK9 inhibitors won't replace statins, since generic statins are widely available at much lower prices. Instead, they will likely be used to complement them.

Upcoming trials to watch
Pfizer's SPIRE-LDL trial, which is expected to be the basis of an eventual BLA submission, is expected to be complete in June 2016. That puts bococizumab on track for a possible approval in 2016 or 2017.

Pfizer's cardiovascular, or CV, risk trials for bococizumab were originally expected to be complete before its rivals' comparable CV trials in 2017. But in late October, Pfizer boosted enrollment in the trials, pushing both completion dates back to 2018. That forfeited Pfizer's CV advantage, since Amgen's and Sanofi/Regeneron's CV trials are also expected to complete in 2018.

Looking ahead into 2015, the only notable trial for bococizumab is SPIRE-SI, which tests the drug in patients who are statin intolerant. The trial is scheduled to be complete next November. Cleveland Clinic Research previously reported that up to 20% of patients suffered some statin intolerance during observational studies. Late-stage trials for alirocumab and evolocumab have already demonstrated that both drugs significantly lowered LDL levels in statin intolerant patients.

A glimmer of hope
Bococizumab clearly won't be the first to market, but there is a glimmer of hope that it could become a "best in class" therapy through Pfizer's partnership with Halozyme (HALO 2.19%).

Halozyme develops human enzymes which carry drugs into the bloodstream. Its main enzyme, called Enhanze, temporarily breaks down hyaluronic acid, a natural substance in the extracellular matrix in the skin and cartilage. Enhanze can improve the efficacy of individual subcutaneous injections.

Pfizer's partnership with Halozyme includes a license for targeting PCSK9 with Enhanze. Delivering bococizumab via Enhanze could reduce necessary doses, giving it an edge over alirocumab and evolocumab, which are also administered subcutaneously. However, delivering the drug via Halozyme's technology will only be relevant after bococizumab is approved.

The road ahead
Bococizumab is clearly the underdog in the PCSK9 race, and it's hard to see the drug matching alirocumab and evolocumab's potential sales without head-to-head comparisons or Halozyme's drug delivery system.

But Pfizer investors shouldn't be discouraged just yet. Palbociclib, which could generate peak sales topping $6 billion per year , could still be approved next April. Meanwhile, other new cancer drugs -- like Xalkori and Inlyta -- continue to post robust double-digit growth.