Pfizer Inc. (NYSE:PFE) announced today top-line results from a double-blind Phase 3 study evaluating pregabalin controlled-release (CR) formulation in adult patients with postherpetic neuralgia (pain after shingles or PHN). The results show that pregabalin CR resulted in a statistically significant positive effect compared to placebo in the primary endpoint, time to loss of therapeutic response (LTR) in pain reduction. PHN is a type of peripheral neuropathic pain caused by nerve damage. Symptoms include continued burning or electric shock-like pain.1
This study is the final of three Phase 3 studies of the pregabalin CR formulation conducted to ascertain the potential use of pregabalin as a once-a-day therapy. The first study in adults with partial onset seizures with epilepsy did not meet its primary endpoint. In the second study in patients with fibromyalgia, pregabalin CR had a statistically significant positive effect compared to placebo in the primary endpoint, time to LTR in pain reduction.
About the Study
The objective of the Phase 3 double-blind, randomized, placebo-controlled study was to evaluate the safety and efficacy of pregabalin CR compared with placebo in the durability of effect for the treatment of pain associated with PHN among patients who initially respond to single-blind pregabalin.
The study was composed of 4 phases: baseline (1 week), single-blind treatment (6 weeks), double-blind treatment (13 weeks), and a 1-week double-blind taper. During the single-blind phase, there were two stratification groups receiving different doses of pregabalin. Patients with normal renal function received a dose between 165 mg/day to 660 mg/day while patients with low renal function received between 82.5 mg/day and 330 mg/day of pregabalin. In the double-blind phase, patients were randomized to continued pregabalin CR treatment at the optimized dose or to matching placebo.
A total of 796 subjects were enrolled into the single-blind phase from 116 sites in 17 countries. Of the 796 subjects, 418 (51.8%) completed the single-blind phase, had ≥50% pain response (i.e., ≥50% reduction in pain compared to baseline) and were randomized into double-blind phase.
The primary endpoint, defined as the time to LTR during the double-blind phase (LTR; <30% pain response relative to the baseline mean pain or withdrawal due to lack of efficacy or adverse events), occurred in 29 of 208 (13.9%) patients in the pregabalin group as compared with 63 of 205 (30.7%) subjects in the placebo group. The difference between the treatments was statistically significant.
Pregabalin CR was well tolerated and the safety profile was consistent with the known profile for pregabalin (immediate release) in PHN patients. The most common adverse events with pregabalin CR were dizziness, somnolence, peripheral edema and weight increase.
Full results from the study will be submitted for publication when analyses are complete.
Lyrica® is currently approved for various indications in 120 countries and regions globally.
Lyrica is approved for five indications in the U.S., of which four are in the therapeutic area of pain. These indications include neuropathic pain associated with diabetic peripheral neuropathy, post-herpetic neuralgia (pain after shingles), neuropathic pain associated with spinal cord injury, fibromyalgia and partial onset seizures in adults with epilepsy who take one or more drugs for seizures.
Lyrica’s ongoing clinical development program is focused on the significant unmet needs of patients with certain chronic pain conditions.
Antiepileptic drugs (AEDs), including Lyrica, increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication. There have been post-marketing reports of angioedema and hypersensitivity with Lyrica. Treatment with Lyrica may cause dizziness, somnolence, dry mouth, edema and blurred vision. Other most common adverse reactions include weight gain, constipation, euphoric mood, balance disorder, increased appetite and thinking abnormal (primarily difficulty with concentration/attention).
For Lyrica prescribing information in the U.S. visit www.lyrica.com.
Important Safety Information
LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its other components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy.
There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms.
There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms.
Antiepileptic drugs (AEDs) including LYRICA increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses showed clinical trial patients taking an AED had approximately twice the risk of suicidal thoughts or behavior than placebo treated patients. The estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one patient for every 530 patients treated with an AED.
The most common adverse reactions across all LYRICA clinical trials are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, constipation, euphoric mood, balance disorder, increased appetite, and thinking abnormal (primarily difficulty with concentration/attention).
Inform patients taking LYRICA that dizziness and somnolence may impair their ability to perform potentially hazardous tasks such as driving or operating complex machinery until they have sufficient experience with LYRICA to determine its effect on cognitive and motor function.
In controlled studies, a higher proportion of patients treated with LYRICA reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions.
Higher frequency of weight gain and edema was observed in patients taking both LYRICA and thiazolidinedione antidiabetic drugs. Exercise caution when coadministering these drugs. Patients who are taking other drugs associated with angioedema such as angiotensin converting enzyme inhibitors (ACE- inhibitors) may be at increased risk of developing angioedema. Exercise caution when using LYRICA in patients who have had a previous episode of angioedema.
LYRICA may exacerbate the effects of oxycodone, lorazepam, or ethanol on cognitive and gross motor functioning.
Patients with a history of drug or alcohol abuse may have a higher chance of misuse or abuse of LYRICA.
Withdraw LYRICA gradually over a minimum of 1 week. Discontinue LYRICA immediately in patients with symptoms of hypersensitivity or angioedema.
Patients with a creatinine clearance of 30 to 60 mL/min had a greater incidence of discontinuation due to adverse reactions than patients with normal creatinine clearance. Adjust the daily dose of LYRICA for patients with reduced renal function (creatinine clearance ≤60 mL/min) and in those undergoing hemodialysis. Administer a supplemental dose of LYRICA immediately following every 4-hour hemodialysis treatment.
In standard, preclinical in vivo lifetime carcinogenicity studies of LYRICA, an unexpectedly high incidence of hemangiosarcoma was identified in 2 different strains of mice. The clinical significance of this finding is unknown. In clinical studies across various patient populations comprising 6396 patient-years of exposure in patients >12 years of age, new or worsening preexisting tumors were reported in 57 patients.
Please see full LYRICA prescribing information at www.LYRICA.com.
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DISCLOSURE NOTICE: The information contained in this release is as of December 18, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about a potential additional indication for Lyrica as a once-a-day treatment, including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development; whether and when any new drug applications may be filed in any jurisdictions for such additional indication for Lyrica; whether and when regulatory authorities in such jurisdictions will approve any such applications, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of such additional indication for Lyrica; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com.
1 UCSF Medical Center. Post-Herpetic Neuralgia. Last accessed at http://www.ucsfhealth.org/conditions/post-herpetic_neuralgia/. on 25 July 2014.
Steven Danehy, 212- 733-1538
Ryan Crowe, 212-733-8160