It didn’t take long for the prospects of the launch class of 2018 to take over their categories.

In professional sports it is rare for a new franchise to win a championship right away. Not so much these days in pharma. Four members of the launch class of 2018 led their entire categories in sales by the following year – Biktarvy in HIV, Symdeko in cystic fibrosis, Takhzyro in hereditary angioedema, and Parsabiv in hyperparathyroidism in patients with CKD. Biktarvy has been particularly impressive, passing $1 billion in sales even before the drug’s first full year on the market and taking over for stablemate Genvoya as the world’s leading HIV product last year. Biktarvy’s quarterly sales continue to grow in 2020, with $6 billion in annual sales well within reach. The Vegas Golden Knights’ run to the Stanley Cup Finals in their first season may have been an aberration in hockey, but such runs are becoming commonplace among pharma brands. 

Biktarvy

Gilead’s Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) was approved by FDA in February 2018 and by the European Commission in June 2018. Biktarvy was approved as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. The product combines the novel, unboosted integrase strand transfer inhibitor (INSTI) bictegravir, with the demonstrated safety and efficacy profile of Gilead’s Descovy (FTC/TAF) dual nucleoside reverse transcriptase inhibitor (NRTI) backbone, and was, as of its approval, the smallest INSTI-based triple-therapy STR available.

Biktarvy became the top new-to-brand HIV regimen in the United States in the product’s second full quarter on the market, overtaking fellow Gilead drug Genvoya. Biktarvy also passed Genvoya as the most successful HIV launch in history as measured by the first four full quarters of sales, by a count of $1.94 billion for Biktarvy compared to $1.48 billion for Genvoya.

The marketing approval of Biktarvy was supported by data from four Phase III studies: Studies 1489 and 1490 in treatment-naïve HIV-1 infected adults, and Studies 1844 and 1878 in virologically suppressed adults. The trials comprised a diverse population of 2,415 participants, including a wide range of adult age groups and races/ethnicities. Biktarvy met its primary objective of non-inferiority at 48 weeks across all four studies. Through 48 weeks, no participants in any of the four studies failed Biktarvy with treatment-emergent virologic resistance, no patients discontinued Biktarvy due to renal adverse events, and there were no cases of proximal renal tubulopathy or Fanconi syndrome.

In Study 1489, a total of 629 treatment-naïve adults with HIV were randomized 1:1 to receive Biktarvy or abacavir/dolutegravir/lamivudine (600/50/300mg) (ABC/DTG/3TC). At Week 48, 92.4 percent of patients taking Biktarvy and 93 percent of patients taking ABC/DTG/3TC achieved the primary endpoint of HIV-1 RNA <50 c/mL. In Study 1490, a total of 645 treatment-naïve adults with HIV were randomized 1:1 to receive Biktarvy or DTG+FTC/TAF. At Week 48, 89.4 percent of patients taking Biktarvy and 92.9 percent of patients taking DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA <50 c/mL.

In Study 1878, a total of 577 virologically suppressed (HIV-1 RNA <50 c/mL) adults with HIV taking regimens of a boosted protease inhibitor (bPI; atazanavir or darunavir) plus a dual-NRTI backbone (ABC/3TC or FTC/tenofovir disoproxil fumarate) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated Biktarvy once daily. At the primary endpoint of Week 48, switching to Biktarvy was non-inferior to continuing on a bPI regimen with 1.7 percent of patients in each group having HIV-1 RNA ≥50 c/mL; the proportion of patients with HIV-1 RNA <50 c/mL was 92.1 percent in the Biktarvy arm and 88.9 percent in the bPI arm, according to FDA snapshot algorithm.

During March 2018, Gilead announced detailed 48-week results from Study 1844 evaluating the efficacy and safety of switching from a regimen containing abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) to Biktarvy, in virologically suppressed adults with HIV. Through Week 48, Biktarvy was found to be statistically non-inferior to ABC/DTG/3TC with a numerically lower incidence of mild or moderate study drug-related adverse events and no treatment-emergent resistance.

Additionally in March 2018, Gilead announced 48-week results from another Phase III study, Study 1961 of 470 virologically suppressed adult women with HIV infection, evaluating the efficacy and safety of switching from a boosted protease inhibitor (bPI) or boosted elvitegravir-containing regimen to Biktarvy. In the ongoing study, Biktarvy was found to be statistically non-inferior to regimens containing a bPI or boosted elvitegravir and demonstrated no treatment-emergent resistance at 48 weeks.

In October 2018, Gilead announced 96-week results from Study 1489 evaluating the safety and efficacy of Biktarvy for the treatment of HIV-1 infection in treatment-naïve adults. In the ongoing study, Biktarvy was found to be statistically non-inferior to a regimen of abacavir/dolutegravir/lamivudine (600/50/300mg, ABC/DTG/3TC) through 96 weeks of therapy.

In March 2019, Gilead announced 48-week results from a Phase II/III study, Study GS-US-380-1474, evaluating the efficacy and safety of Biktarvy in virologically suppressed adolescents and children at least 6 years of age who are living with HIV. Through Week 48, Biktarvy maintained high rates of virologic suppression with a low incidence of study drug-related adverse events and no treatment-emergent resistance.

Also in March 2019, Gilead announced data from two studies evaluating the resistance profile of Biktarvy in virologically suppressed adults switching from dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) or a boosted protease inhibitor (PI)-based regimen for the treatment of HIV-1. The studies found high rates of virologic suppression with Biktarvy in treatment-experienced adults, regardless of pre-existing resistance to NRTIs.

In July 2019, Gilead presented findings from two Phase III trials – a trial demonstrating the effectiveness of switching to Biktarvy in women, and a trial evaluating the potential for the single tablet regimen to be an effective treatment option in virologically suppressed patients with known resistance to NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

The first trial evaluated 470 virologically suppressed women on a baseline regimen of either Genvoya, elvitegravir/cobicistat/F/TDF (150/150/200/300 mg), or atazanavir+ritonavir+F/TDF (300+100+200/300 mg) who switched 1:1 from these baseline regimens to Biktarvy. At Week 96, 99.5 percent of women who received Biktarvy throughout the study duration and 98.5 percent of women who switched to Biktarvy at Week 48 maintained virologic suppression, with no development of treatment-emergent resistance.

The second trial evaluated 565 virologically suppressed adults who switched 1:1 from a regimen of DTG+F/TAF (50+200/25 mg) or DTG+F/TDF (50+200/300 mg) to DTG+F/TAF or Biktarvy for 48 weeks. Unlike previous studies – which excluded participants with known resistance – participants in this study with prior resistance to NRTIs, NNRTIs, and/or protease inhibitors (PIs) could enroll. Only those participants with documented integrase inhibitor resistance were excluded, and 24 percent of participants had resistance to NRTIs. At Week 48, 0.4 percent of participants on Biktarvy had HIV-1 RNA ≥ 50 c/ml, compared to 1.1 percent of participants on DTG+F/TAF (snapshot algorithm), demonstrating noninferiority. In addition, at Week 48, no treatment-emergent resistance was detected, and no participants with pre-existing NRTI resistance mutations had HIV RNA >50 c/mL.

In November 2019, Gilead announced further findings from Studies 1489 and 1490 showing that Biktarvy was well-tolerated and demonstrated high rates of virologic suppression through week 144.

In March 2020, Gilead announced data from the BRAAVE 2020 study, a Phase III clinical trial evaluating the safety and efficacy of switching to Biktarvy in virologically suppressed adults living with HIV who self-identified as Black or African American. The data show that, at 24 weeks, switching to Biktarvy from a standard regimen of two NRTIs plus a third agent may potentially be an effective and well-tolerated treatment regimen in patients with a history of treatment failure or pre-existing resistance, and did not result in treatment emergent resistance to study drugs with Biktarvy. Gilead also announced results of a pooled analysis from Studies 1489 and 1490 showing Biktarvy continued to be highly effective and well-tolerated in treatment-naïve patients age 50 and older over three years of treatment. Importantly, participants experienced no clinically significant differences in key measures such as bone density, renal laboratory markers or weight.

During July 2020, Gilead announced data showing the safety and efficacy of the once-daily, single tablet regimen Biktarvy in virologically suppressed adults ages 65 and older, including those with common comorbidities such as diabetes (22 percent), hypertension (55 percent), cardiovascular disease (24 percent), and dyslipidemia, which is an abnormal amount of lipids in the blood (59 percent). At 48 weeks, 92 percent of those who switched to Biktarvy maintained virologic suppression, achieving HIV RNA<50 copies/mL.

Ozempic

Approved by FDA in December 2017 and launched in the United States in February 2018, Novo Nordisk’s Ozempic (semaglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The product was also approved by the European Commission in February 2018 and in Japan during the following month. The approval of Ozempic was based on the results from the SUSTAIN clinical trial program. In people with type 2 diabetes, Ozempic produced clinically meaningful and statistically significant reductions in HbA1c compared with placebo, sitagliptin, exenatide extended-release, and insulin glargine U100. Furthermore, in the clinical trials, treatment with Ozempic resulted in statistically significant reductions in body weight. Ozempic demonstrated a safe and well-tolerated profile across the SUSTAIN program with the most common adverse event being mild-to-moderate nausea, which diminished over time.

In June 2018, Novo Nordisk announced study results showing that Ozempic 0.5 mg or 1.0 mg provided greater weight reductions versus dulaglutide 0.75 mg or 1.5 mg, respectively, in adults with type 2 diabetes, regardless of baseline body mass index, with the greatest reductions occurring in adults with a baseline BMI >25 kg/m2. While the primary endpoint of the study, SUSTAIN 7, was change in HbA1c, this post-hoc exploratory analysis examined the secondary endpoint of change in body weight by baseline BMI.

Greater weight reductions were demonstrated across all BMI subgroups (<25, 25-<30, 30-<35, >35 kg/m2) with Ozempic 0.5 mg vs dulaglutide 0.75 mg (range of weight reduction across all subgroups: 3.6-5.5 kg vs 0.9-3.4 kg) and with Ozempic 1.0 mg vs dulaglutide 1.5 mg (range of weight reduction across all subgroups: 5.2-7.6 kg vs 2.0-3.8 kg), from a mean baseline of 95.2 kg. Adults with a higher baseline BMI (>25 kg/m2) taking Ozempic generally achieved greater weight reductions than those with lower baseline BMI (<25 kg/m2). In addition, more people achieved weight reductions of >5 percent and >10 percent with Ozempic versus dulaglutide in all BMI subgroups.

In August 2018, Novo Nordisk announced data showing that Ozempic consistently reduced the risk of the composite outcome of time to first occurrence of non-fatal heart attack, non-fatal stroke, or cardiovascular death (collectively termed major adverse cardiovascular events, MACE) in people with type 2 diabetes at high cardiovascular risk regardless of previously having had a cardiovascular event at the start of the trial.

The SUSTAIN 6 post-hoc analyses found that reduction in the risk of MACE was consistent in people at high cardiovascular risk treated with Ozempic regardless of their cardiovascular risk profile at the start of the trial, including whether or not they had a prior heart attack or stroke, and whether they had cardiovascular risk factors or established cardiovascular disease. SUSTAIN 6 was a pre-approval cardiovascular outcomes trial in 3,297 people with type 2 diabetes and established cardiovascular disease or with at least one cardiovascular risk factor, compared to placebo, both in addition to standard of care.

The post-hoc pooled meta-analysis of the SUSTAIN 1-5 efficacy trials, which included 4,807 people, trended towards a lower risk of MACE in people taking Ozempic. The comparators included in SUSTAIN 1-5 were placebo, sitagliptin, exenatide extended release, and insulin glargine U100. The overall incidence of MACE was low across the SUSTAIN 1-5 trials and, due to the low number of events, this reduction did not achieve statistical significance.

In November 2018, Novo Nordisk announced the headline results from the last global phase IIIa trial, PIONEER 6, for oral semaglutide, a tablet formulation of the injectable Ozempic. This double-blinded trial investigated the cardiovascular safety of oral semaglutide 14 mg compared with placebo, both in addition to standard of care, in 3,183 adults with type 2 diabetes at high risk of cardiovascular events.

The trial achieved its primary endpoint by demonstrating non-inferiority of major adverse cardiovascular events with oral semaglutide compared with placebo, both in addition to standard of care. The results are based on the accumulated occurrence of 137 major adverse cardiovascular events, with a median follow-up time of 16 months. The primary endpoint of the PIONEER 6 trial was defined as the MACE composite outcome of the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke and showed a hazard ratio of 0.79 in favor of oral semaglutide compared with placebo. The 21 percent reduction in MACE in favor of oral semaglutide did not reach statistical significance.

The MACE results demonstrated by oral semaglutide were driven by a statistically significant reduction in cardiovascular death of 51 percent, while non-fatal myocardial infarction (HR 1.18, non-significant) or non-fatal stroke (HR 0.74, non-significant) were broadly similarly distributed between the two treatment arms. In addition, a statistically significant reduction in all-cause mortality of 49 percent in favor of oral semaglutide was observed.

The improvements in secondary endpoints including HbA1c, body weight and blood pressure were similar to results reported throughout the PIONEER program for oral semaglutide. Furthermore, the safety profile of oral semaglutide in PIONEER 6 was consistent with the established safety profile observed in previous PIONEER studies.

In March 2019, Novo Nordisk submitted two new drug applications to FDA for oral semaglutide, as well as a supplemental NDA for once-weekly Ozempic. An NDA was submitted for oral semaglutide seeking marketing approval for an indication for the treatment of adults with type 2 diabetes. 

The first submission for oral semaglutide, for the treatment of glycemic control in adults with type 2 diabetes, was based on the results from 10 PIONEER clinical trials, which included 9,543 adults with type 2 diabetes. In the PIONEER program, people treated with oral semaglutide achieved greater blood glucose reductions compared to sitagliptin, empagliflozin, liraglutide, and placebo. In addition, oral semaglutide demonstrated greater reductions in mean body weight versus most comparators. This application was subsequently approved by FDA in September 2019 and oral semaglutide was launched with the brand name Rybelsus. 

The second NDA and the sNDA were seeking approval for a cardiovascular risk reduction indication in adults with type 2 diabetes. These were based on the results of two cardiovascular outcomes trials (CVOTs) evaluating the effects of adding semaglutide or placebo to standard of care on the risk of cardiovascular events; PIONEER 6 with oral semaglutide and SUSTAIN 6 with Ozempic. These applications were subsequently approved by FDA in January 2020. 

Symdeko

Vertex Pharmaceuticals’ Symdeko, (tezacaftor/ivacaftor and ivacaftor), indicated for treating the underlying cause of cystic fibrosis in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor, was approved by FDA in February 2018. Symdeko’s component ivacaftor is marketed on its own as Kalydeco. The combination treatment’s initial approval was based on two Phase III studies, EVOLVE and EXPAND, which enrolled approximately 750 people with CF ages 12 and older with two copies of the F508del mutation or with one F508del mutation and one mutation that results in residual CFTR function. Across both studies, patients treated with Symdeko experienced statistically significant and clinically meaningful improvements in lung function and other measures of disease, with a favorable safety profile. The first data from the ongoing EXTEND rollover study also showed that the lung function improvements and the safety and tolerability profiles seen in EVOLVE and EXPAND were sustained for up to 48 total weeks of Symdeko treatment. Symdeko was subsequently approved by the European Commission in November 2018 under the brand name Symkevi.

During November 2018, Vertex announced that treatment with the triple combination of the next-generation corrector VX-659, tezacaftor and ivacaftor resulted in statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in two Phase III studies in people with cystic fibrosis. Data from a pre-specified interim analysis of the Phase III study in people with one F508del mutation and one minimal function mutation showed a mean absolute improvement in ppFEV1 of 14.0 percentage points from baseline at week 4 of treatment compared to placebo. In the Phase III study in people with two F508del mutations, the addition of VX-659 in patients already receiving tezacaftor and ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10.0 percentage points from baseline at week 4 of treatment compared to the control group in whom placebo was added to tezacaftor and ivacaftor.

In March 2019, Vertex announced that treatment with the triple combination of the next-generation corrector VX-445, tezacaftor, and ivacaftor resulted in statistically significant improvements in ppFEV1 in two Phase III studies in people with cystic fibrosis. Data from a pre-specified interim analysis of the Phase III study in people with one F508del mutation and one minimal function mutation showed a mean absolute improvement in ppFEV1 of 13.8 percentage points from baseline at week 4 of treatment compared to placebo. In the Phase III study in people with two F508del mutations, the addition of VX-445 in patients already receiving tezacaftor and ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10.0 percentage points from baseline at week 4 of treatment compared to the control group in whom placebo was added to tezacaftor and ivacaftor. In May 2019, the company announced that Vertex would be submitting the triple combination of VX-445 (elexecaftor), tezacaftor, and ivacaftor for potential global regulatory approvals for people ages 12 and older with cystic fibrosis. The triple combination was subsequently approved for marketing by FDA in October 2019 under the brand name Trikafta. 

In June 2019, FDA approved Symdeko for use in children with cystic fibrosis ages 6 through 11 years who have two copies of the F508del-CFTR mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeko. An additional dosage strength of Symdeko tablets was made available (tezacaftor 50 mg/ivacaftor 75 mg and ivacaftor 75 mg) in connection with this approval. Vertex completed a 24-week Phase III open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of tezacaftor/ivacaftor and ivacaftor in children ages 6 through 11 years in the United States and Canada. 

Takhzyro

Approved by FDA in August 2018 and the European Commission three months later, Takhzyro (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years of age and older. HAE is a rare, genetic and potentially life-threatening disorder that can result in recurrent attacks of edema (swelling) in various parts of the body. The product was initially brought to market by Shire, but is now marketed by Takeda after the acquisition of Shire in January 2019. 

Takhzyro is the only monoclonal antibody (mAb) that provides targeted inhibition of plasma kallikrein, an enzyme which is chronically uncontrolled in people with HAE, to help prevent attacks. In the Phase III HELP (Hereditary Angioedema Long-term Prophylaxis) Study supporting FDA approval, Takhzyro reduced the number of monthly HAE attacks an average of 87 percent versus placebo when administered at 300 mg every two weeks and 73 percent versus placebo when administered at 300 mg every four weeks.

In the 26-week clinical study, which included 125 people with HAE, patients taking Takhzyro 300 mg every two weeks also had 83 percent fewer moderate to severe attacks, and 87 percent fewer attacks that needed on-demand treatment. A pre-specified, exploratory analysis showed that 44 percent of patients receiving Takhzyro 300 mg every two weeks had zero attacks compared to placebo for the 26-week treatment period from Day 0 to Day 182. Additionally, in a post hoc analysis of the 16-week period from Day 70 to Day 182, 77 percent of patients treated with Takhzyro in the same dosage arm of the trial were attack-free compared to placebo.

In June 2019, Takeda announced new data from an ad-hoc analysis of the Phase III HELP Study, designed to evaluate the onset of action for Takhzyro during days 0-69 of treatment. The analysis suggested that Takhzyro starts to prevent hereditary angioedema attacks during this early treatment phase, with patients experiencing an 80.1 percent decrease in mean monthly attack rate compared to placebo.

The ad-hoc analysis evaluated the efficacy of Takhzyro compared with placebo during days 0-69 of treatment using the same approach that was used to evaluate the primary and secondary endpoints during the complete study period (days 0-182). Results from the analysis showed that in patients receiving the recommended starting dose of Takhzyro 300 mg every two weeks, there was a significant reduction in mean monthly attack rate (80.1 percent decrease) compared to placebo. During this initial treatment phase, patients treated with Takhzyro 300 mg every two weeks also experienced fewer severe attacks compared to placebo (7.4 percent versus 22 percent) and were more likely to be HAE attack-free compared to those on placebo (48.1 percent versus 7.3 percent). Across all Takhzyro treatment arms, (300 mg every two weeks, 300 mg every four weeks, 150 mg every four weeks), there was an improvement in mean monthly attack rate, monthly rate of moderate-to-severe attacks, monthly rate of attacks requiring acute treatment, and the number of attack-free days, versus placebo, during the entire study period.

During November 2019 Takeda announced new data that further investigated the long-term safety and efficacy of Takhzyro in patients with hereditary angioedema 12 years of age and older studied in the ongoing Phase III HELP Study Open-label Extension. The analyses showed that Takhzyro continued to prevent HAE attacks at a rate similar to that observed in the pivotal HELP Study, in patients who received treatment for a mean duration of 19.7 (0-26.1) months.

Results from the HELP Study OLE showed that the safety profile of Takhzyro was consistent with the original findings from the HELP Study, with treatment-related treatment emergent adverse events (TEAEs) occurring in 50 percent of patients. In addition, Takhzyro 300 mg every two weeks reduced the rate of attacks, attacks requiring acute treatment, and moderate to severe attacks (secondary efficacy endpoints). The mean attack rate was reduced by 87 percent overall compared with baseline. Similarly there was an overall reduction of 92.6 percent in the rate of attacks requiring acute treatment and 83.6 percent in the rate of moderate/severe attacks versus baseline. An exploratory analysis showed that the overall maximum attack-free period lasted ≥12 months in 58 percent of patients and ≥6 months in 78 percent of patients following the first regular treatment dose.

Parsabiv

Amgen’s Parsabiv was approved by FDA in February 2017 and launched in the United States in the first quarter of 2018 for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Parsabiv was the first therapy approved for this condition in 12 years and the only calcimimetic that can be administered intravenously by the dialysis health care team three times a week at the end of the hemodialysis session. The product was approved by the European Commission in November 2016 and by regulatory authorities in Japan the following month. 

Often occurring in patients in Stage 5 of CKD, secondary HPT refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to decreased renal function and impaired mineral metabolism. Parsabiv binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH.

Secondary HPT is a serious condition and the proportion of patients unable to reach recommended secondary HPT lab targets has more than doubled in the last five years. Amgen’s Sensipar, the first FDA-approved calcimimetic, became an important treatment for patients with secondary HPT on dialysis based on its ability to reduce three important biochemical abnormalities (PTH, calcium, phosphorus). Parsabiv is a novel calcimimetic that can be delivered intravenously at the end the hemodialysis session and has been demonstrated to effectively reduce levels of PTH, corrected calcium and phosphate. These reductions were maintained for up to 78 weeks.

The U.S. approval of Parsabiv was largely based on data from two placebo-controlled Phase III studies, both of which met their primary endpoints.

In the two 26-week, randomized, double-blind, placebo-controlled studies, an aggregate of 1,023 patients with moderate-to-severe secondary HPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week, at the end of their dialysis sessions in addition to standard of care that could include vitamin D and/or phosphate binders. The primary endpoint of both studies was the proportion of patients achieving greater than 30 percent reduction from baseline in PTH during the Efficacy Assessment Phase (EAP), defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300 pg/mL during the EAP; and percent reductions in PTH, albumin-adjusted calcium (cCa), phosphate (P) and cCa x P during the EAP.

The two studies showed that significantly more Parsabiv than placebo patients, respectively, achieved a greater than 30 percent reduction from baseline in PTH during the EAP: 77 percent versus 11 percent in Study 1, and 79 percent versus 11 percent in Study 2. Significantly more Parsabiv than placebo patients also achieved PTH levels of 300 pg/mL or less during the EAP: 52 percent versus 6 percent in Study 1, and 56 percent versus 5 percent in Study 2. Additionally, greater percent reduction from baseline was achieved in Parsabiv-treated patients than placebo-treated patients during the EAP, for PTH, corrected calcium and phosphate in both studies.

In a pooled analysis of the two Phase III placebo-controlled studies, asymptomatic reductions in serum calcium and symptomatic hypocalcemia occurred more frequently in patients treated with Parsabiv compared to placebo (64 percent versus 10 percent, and 7 percent versus 0.2 percent, respectively).