Pfizer 1Q16 – Phase 3 data for SGLT-2 inhibitor ertugliflozin to be presented at ADA; SPIRE-2 CV outcomes trial for PCSK9 inhibitor bococizumab fully enrolled; Phase 2 PDE5 inhibitor for diabetic nephropathy discontinued – May 3, 2016

Pfizer provided its 1Q16 update this morning in a call led by CEO Mr. Ian Read. The call’s most notable diabetes-related update was the announcement that phase 3 data for the company’s Merck-partnered SGLT-2 inhibitor ertugliflozin will be presented at ADA in June. We also learned that one of the two cardiovascular outcomes trials for PCSK9 inhibitor bococizumab – SPIRE-2 – is now fully enrolled, with results potentially available in the second half of 2017. While not mentioned on the call, Pfizer also discontinued development of its PDE5 inhibitor PF-00489791 for diabetic nephropathy in 1Q16. See below for our top three highlights from the call, followed by relevant Q&A.

1. Pfizer shared that phase 3 data for Merck-partnered SGLT-2 inhibitor ertugliflozin will be presented at ADA.

2. Management noted that one of the two cardiovascular outcomes trials for PCSK9 inhibitor bococizumab, SPIRE-2, is now fully enrolled.

3. Disappointingly, Pfizer has discontinued development of PF-00489791, its phase 2 PDE5 inhibitor for diabetic nephropathy.

Top Three Highlights

1. Pfizer shared that phase 3 data for Merck-partnered SGLT-2 inhibitor ertugliflozin will be presented at ADA. The call also reiterated that the company hopes to submit ertugliflozin to the FDA in 2016. Pfizer previously shared that the partnership’s phase 3 ertugliflozin/sitagliptin and ertugliflozin/metformin fixed-dose combinations will also be submitted this year. Ertugliflozin will be the fourth-to-market SGLT-2 inhibitor, after J&J’s Invokana (canagliflozin), AZ’s Farxiga (dapagliflozin), and Lilly/BI’s Jardiance (empagliflozin), and we’ll be interested to see how Pfizer and Merck plan to differentiate it in this fairly crowded competitive landscape. The companies’ phase 3 development program does include a trial in patients with type 2 diabetes and stage 3 chronic kidney disease (eGFR >30 and <60; primary endpoint of A1c reduction, expected completion in September 2016 according to ClinicalTrials.gov). Based on these data, we imagine Pfizer/Merck could pursue an indication for patients with impaired renal function. Currently available SGLT-2 inhibitors are either not recommended or contraindicated in patients with impaired renal function due to decreased efficacy, so ertugliflozin could potentially find a competitive niche within the market if it can demonstrate sufficient A1c-lowering efficacy in these patients. Furthermore, we imagine the ertugliflozin/sitagliptin combination could prove popular as the sitagliptin component (Merck’s Januvia) is the DPP-4 inhibitor with the most reassuring CV safety profile demonstrated in a dedicated outcomes trial thus far. That said, ertugliflozin will be competing with at least one agent (Jardiance) that has already demonstrated a cardioprotective benefit; its CVOT is not expected to complete until 2020.

2. Management noted that one of the two cardiovascular outcomes trials for PCSK9 inhibitor bococizumab, SPIRE-2, is now fully enrolled. The company expects the trial to potentially complete in the second half of 2017. This is a more ambitious timeline than the completion date of March 2018 posted on ClinicalTrials.gov. The other CV outcomes trial, SPIRE-1, is still enrolling participants and is expected to complete in June 2018 according to ClinicalTrials.gov. In Q&A, management reiterated Pfizer’s belief that positive CV outcomes results are necessary to catalyze uptake of the PCSK9 inhibitor class, especially at the current high list prices (~$14,000/year).

• Results from the phase 3 SPIRE-AI trial for bococizumab were reported in April. The 12-week, double-blind, placebo-controlled, randomized trial (n=299 patients on statins with LDL ≥70 mg/dl) met its dual primary endpoints of (i) greater percent reduction in LDL cholesterol vs. placebo after 12 weeks and (ii) greater percentage of patients who successfully self-administered bococizumab with the auto-injector pen compared to placebo.

3. Disappointingly, Pfizer has discontinued development of PF-00489791, its phase 2 PDE5 inhibitor for diabetic nephropathy. As recently as last quarter, this candidate was listed as a “key program” on the company’s product pipeline. However, we had not heard any updates on it since 3Q14, when Pfizer noted that it had “encouraging” phase 2 data. We presume the efficacy and safety profile of the candidate didn’t quite meet the bar to advance it into a very long and expensive phase 3 development program. Even so, we’re very disappointed to see this go given the high unmet need in this area – see our competitive landscape for an overview of the other companies developing products for this indication. This news is the latest in a string of attritions within Pfizer’s early-stage development pipeline. In 4Q15, the company removed its phase 2 partial glucokinase activator PF-04937319 from its pipeline. In 3Q15, Pfizer dropped its phase 2 CCR2/5 antagonist PF-04632817 for diabetic nephropathy and diabetic macular edema. It appears that Pfizer may be moving away from developing drugs for diabetes complications, as it now has no candidates for complications in its product pipeline. We certainly hope this doesn’t signal a larger shift away from diabetes as a whole and would imagine that ertugliflozin’s performance may influence the company’s thinking around diabetes moving forward.

• Diabetes-related candidates that remain in Pfizer’s early-stage pipeline include a glucagon receptor antagonist (PF-06291874) for type 2 diabetes in phase 2, an undisclosed biologic (PF-06293620) for type 2 diabetes in phase 1, and an undisclosed biologic (PF-06342674) for type 1 diabetes in phase 1. Pfizer also added an oral PCSK9 inhibitor to its phase 1 pipeline in 4Q15.

Questions and Answers

Q: For bococizumab and PCSK9 inhibitors outcomes data are clearly going to dictate the market share. But how much of a role do you think intravascular ultrasound (IVUS) imaging will play in product differentiation?

A: I've always thought that these products should only have been launched when you have outcomes data. We've always said that on LDL-lowering alone, it will be difficult to convince society to pay what's necessary, and you really need to include outcomes data as well. So clearly outcomes data is important. IVUS imaging has been used previously with lipid agents, but it doesn't really move the needle. What moves the needle is the large prospective trials that show that an impact on outcomes. An image just doesn't do the same as that data. Overall, I look forward to that class expanding when we have the outcomes data and we have the right value equation for society.

-- by Helen Gao, Emily Regier, and Kelly Close