Regeneron's Dupixent Faces Peak Growth Concerns Amid COPD Challenges; Bispecific Antibody REGN1979 Linked to Two Patient Deaths

Regeneron reported its first-quarter 2019 financial results yesterday (May 7), with total revenues of $1.71 billion, a 13% increase compared to the first quarter of 2018, and net income of $460 million. This revenue figure fell short of Wall Street’s previous estimate of $1.77 billion, largely due to lower-than-expected collaboration revenues from Sanofi.

Dr. Leonard S. Schleifer, President and Chief Executive Officer of Regeneron, stated, “In the first quarter of this year, total sales of all Regeneron-invented products amounted to $2.27 billion, representing a 23% increase compared to the same period last year. Key growth drivers included the ophthalmic injection Eylea (with an 8% net sales increase), Dupixent (with a 185% net sales increase), and the initial approval of Libtayo for the treatment of advanced cutaneous squamous cell carcinoma. Dupixent has now received U.S. FDA approval for atopic dermatitis and asthma in adults and adolescents, and is currently under priority review by the FDA for chronic rhinosinusitis with nasal polyps. The company will continue to explore and leverage the full potential of this product while further investing in its broad immuno-oncology portfolio.”

However, as Phase 3 trials for chronic obstructive pulmonary disease (COPD) progress, Schleifer also indicated that the challenges in securing regulatory approval for Dupixent’s COPD indication may continue to increase.

Dupixent’s Growth Potential May Quickly Peak, While Eylea and Libtayo Sustain the Overall Performance

In the first quarter of 2019, Dupixent sales exceeded analysts’ previous expectations, with U.S. sales alone reaching $303 million. During a conference call with analysts, Marion McCourt, Senior Vice President at Regeneron, stated that total prescriptions for the drug increased by approximately 18%. Since the drug received U.S. FDA approval in October 2018 and entered the biologics market for asthma patients, this performance growth was partly driven by an expansion of its indications. McCourt noted, “Approximately three-quarters of asthma patients treated with Dupixent are using this biologic for the first time, so continued future growth remains a significant opportunity.” Meanwhile, on Tuesday (May 7), the European Union officially announced approval for the treatment of asthma, which is likely to further boost the drug’s sales in the future.

Dupixent has helped Regeneron enhance its overall influence in the fields of asthma and adolescent eczema treatment; however, Schleifer noted that signs of greater difficulty have emerged in the drug’s plan to expand its indication for COPD.

Dupixent is a fully human monoclonal antibody that specifically inhibits the overactivated signaling of two key proteins, IL-4 and IL-13. IL-4 and IL-13 are inflammatory cytokines considered to be key drivers of allergic diseases and other inflammatory conditions, including atopic dermatitis, asthma, eosinophilic esophagitis, grass pollen allergy, and peanut allergy.

Regeneron President and Chief Scientific Officer George Yancopoulos stated in the first quarter of this year, “Both clinical data and real-world experience indicate that dual IL-4 and IL-13 inhibitors can provide symptomatic relief and therapeutic benefits for patients with various inflammatory diseases.” However, COPD is a distinctly different and highly complex disease. Many COPD patients experience exacerbations driven by IL-4 and IL-13-mediated inflammation; therefore, the key challenge lies in identifying appropriate patient populations for clinical trials and engaging regulatory authorities from a position of strength as a potential disease-modifying therapy. The mechanism of action of Dupixent is associated with the reduction of IL-4 and IL-13 inflammatory biomarkers, including fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE), and eotaxin-3 (CCL26). Previous studies have shown that chronic obstructive pulmonary disease (COPD) remains a formidable challenge to address. Biologic competitors of Dupixent, such as GlaxoSmithKline’s Nucala and AstraZeneca’s Fasenra, have both encountered failures in this therapeutic area.

Schleifer stated, “Regeneron does not have ‘high confidence’ in Dupixent’s ability to conquer this disease. However, Regeneron has not given up, nor is it blindly confident about future potential outcomes.”

In addition to Dupixent, Eylea, developed in collaboration between Regeneron and Bayer, has been on the market for eight years, with U.S. sales increasing by 9% year-over-year to $1.07 billion. The drug still holds growth opportunities for the indication of diabetic retinopathy, and Regeneron is awaiting regulatory approval decisions. Furthermore, Libtayo, the PD-1 inhibitor co-developed by Regeneron and Sanofi, has established a foothold in the treatment of cutaneous squamous cell carcinoma, achieving first-quarter sales of $27 million. The two companies are actively expanding its indications, focusing on the lucrative first-line lung cancer treatment sector, which is currently dominated by Merck’s Keytruda.

However, Regeneron’s PCSK9 inhibitor Praluent failed to exceed prior expectations in the first quarter of this year, as sales growth ultimately could not offset pricing pressures. The drug recently received an expanded indication, which, combined with its cardiovascular benefits, may provide better opportunities to compete with Amgen’s Repatha in the future.

Oncology R&D Is Far from Worry-Free: Bispecific Antibody Side Effects Lead to Patient Death

Meanwhile, Regeneron executives chose to disclose on Tuesday the fatal cases involving REGN1979, a bispecific antibody under close scrutiny. In a small study involving 30 patients, the drug caused cytokine release syndrome in two patients, ultimately leading to their deaths.

REGN1979 is an IgG4 isotype-based CD20xCD3 bispecific antibody, engineered to reduce Fc binding capacity. It is primarily designed to bind T cells and CD20-expressing cells. Upon binding to both T cells and CD20-expressing tumor cells, the bispecific antibody induces specific local T-cell activation and cytotoxicity, thereby leading to tumor cell killing.

Israel Lowy, Head of Cancer Research at Regeneron, presented trial data on the drug’s treatment of follicular lymphoma at the American Society of Hematology Annual Meeting held in late 2018. The overall response rate was 100%, with eight patients achieving complete remission and two experiencing partial remission. However, these results represent very early data from a small-scale trial.

Regeneron believes that the higher toxicity of cytokine release syndrome (CRS) observed in this trial may be attributed to an enhanced immune response, and it notes that CRS may also be associated with increased tumor efficacy responses. Although this combination therapy has encountered setbacks, Regeneron is confident that it can help control immune activation by titrating doses individually and adjusting the drug sequence, thereby managing the heightened antitumor activity while limiting the potential risk of CRS. Regeneron’s management considers this adjustability in dosing and sequencing to be an advantage of their therapeutic approach over the CAR-T therapies offered by other companies.

Jefferies analyst Biren Amin stated, “Regeneron is expected to update clinical trial data for REGN1979 at the European Hematology Association (EHA) Congress in June, including results from higher-dose cohorts and follow-up data. The company plans to initiate two pivotal registration studies and conduct a combination study with an anti-PD-1 agent in 30 patients with advanced lymphoma.”

Affected by this unfavorable news, the stock price fell 6.5% late Tuesday afternoon, but this was not solely due to panic triggered by the bispecific antibody; a more significant factor was likely the increase in R&D costs and the lukewarm sales performance of Eylea. In addition, the decline in cash flow from partner Sanofi also contributed to the downward trend in Regeneron’s earnings per share and revenue. (Sina)PharmaceuticalsCompiled by Fan Dongdong, edited by Kerr)

Source:

1、Dupixent's on a roll in eczema and asthma, but COPD's a ‘much tougher’ malady: Regeneron CEO

2、Regeneron’s star bispecific is linked to 2 deaths in a small study — which was no help for its Q1 call

3、REGENERON REPORTS FIRST QUARTER 2019 FINANCIAL AND OPERATING RESULTS

Source: Sina Medical News