After a season of regulatory upheaval, obesity and rare genetic diseases will likely remain major themes for biopharma in 2025, according to Jefferies.
The first half of 2025 was six months of policy upheaval.
The Department of Health and Human Services, under the new leadership of Secretary Robert F. Kennedy Jr., has undergone some big changes, not least of which is the large-scale reorganization of the department, involving steep cuts to the FDA, CDC and National Institutes of Health. These changes have not only resulted in delays to drug decision dates but also threaten the development of novel treatments in areas such as HIV.
More recently—and perhaps most controversially—Kennedy last month emptied the CDC’s Advisory Committee on Immunization Practices, the regulator’s highly influential vaccines advisory panel, a move he said was necessary to restore the public’s confidence in the institution. He has since reconstituted the committee, though with fewer members, many of whom are skeptical of vaccines in general.
Still, the biopharma industry has recorded significant wins. In June, for instance, the FDA signed off on Gilead’s Yeztugo, a twice-yearly pre-exposure prophylactic (PrEP) therapy to prevent HIV—an approval analysts at Mizuho at the time said could “redefine the PrEP market.” The industry’s pipeline likewise delivered an encouraging performance overall, with some impactful victories for Merck, Vertex and Lexeo, among other big and small players.
As biopharma moves into the back half of the year, policy headwinds will likely continue to pose high-level challenges to the industry, according to a “Halftime Show” report by Jefferies. Here, BioSpace looks at some of the biggest catalysts and milestones in the coming months.
Lilly Approaches Obesity Readout for Orforglipron
“Obesity should pick up as a major theme in H2,” analysts at Jefferies predicted in their Sunday note. Arguably the hottest company in the space, Eli Lilly has in its hands the most highly anticipated and closely watched asset: the oral GLP-1 agonist orfoglipron.
In the third quarter of this year, the pharma expects to report topline data from the Phase III ATTAIN trial, which is looking at the weight loss potential of orforglipron in adults with obesity or who are overweight and have weight-related comorbidities. According to Jefferies, orforglipron’s readout “should help better define how the obesity market will play out.”
Hopes are high for orforglipron, especially after Lilly in April released late-stage data from a type 2 diabetes study, demonstrating a 1.5% decrease in blood glucose levels at 40 weeks. Though not specifically designed to evaluate weight loss, the study also found that patients on orforglipron shed 7.9% of their weight versus 1.6% of placebo comparators.
Analysts at the time were highly optimistic about these findings. BMO Capital Markets noted that orforglipron had achieved Lilly’s goal of “reaching injectable like efficacy from [an] oral” drug.
Still, some concerns remain. Jefferies, for instance, pointed out in a June 22 note that there appear to be some signs that the drug’s adverse events “don’t improve with time.” William Blair analysts also flagged some safety issues, writing in a June 23 note that they “are concerned by the persistence of both severe and frequent gastrointestinal adverse events beyond the titration period.” BMO was less concerned, calling the drug’s safety data “clean, with only 14% of patients experiencing nausea and 13% vomiting at the highest dose on a placebo adjusted basis.”
Scholar Rock Awaits Spinal Muscular Atrophy Verdict, With Likely Readthrough on Obesity
On or before Sept. 22, the FDA is expected to release its decision on Scholar Rock’s investigational antibody apitegromab, which the Cambridge, Massachusetts–based biotech is proposing for the treatment of spinal muscular atrophy (SMA), a rare genetic disease that affects around 1 in every 6,000 to 11,000 live births.
Apitegromab works by targeting myostatin, a signaling protein that inhibits muscle development. With myostatin blocked, patients can potentially stave off muscle wasting. Through this mode of action, Scholar Rock is hoping that the drug can help improve motor function in patients with SMA. Phase III data released in October last year seem to support that hypothesis. Compared with placebo, patients 2 to 12 years old treated with apitegromab saw a 1.8-point improvement on the Hammersmith Functional Motor Scale Expanded, a tool the biotech at the time said was the “gold standard” for measuring motor function in this disease.
An approval for apitegromab will not only give Scholar Rock a solid footing in the SMA space but will also potentially have some positive readthrough to preserving muscle alongside obesity medications, an indication for which the company is also proposing apitegromab. Mid-stage data last month showed that when used alongside Lilly’s tirzepatide, marketed for weight loss as Zepbound, apitegromab preserves 55% more lean muscle mass than tirzepatide alone.
In a June 18 note, Jefferies analysts wrote that an SMA nod would be a “major de-risking event” for apitegromab.
Hunter Syndrome Decisions for Denali, Regenxbio Test New FDA on Rare Disease
Aside from Scholar Rock, the rare disease space is looking at two more key decisions in the next six months or so, both for Hunter syndrome.
A genetic disorder, patients with Hunter syndrome are unable to break down certain sugars, causing a damaging buildup across various tissues. The disease almost always occurs in boys, affecting around 1 of every 100,000 to 170,000.
One of these decisions is for Regenxbio, which is proposing its gene therapy clemidsogene lanparvovec as a one-time treatment for the disease. Phase I/II/III findings demonstrated an 86% drop in cerebrospinal fluid levels of DS26, a key biomarker of Hunter syndrome activity in the brain. Regenxbio expects a decision from the FDA on an application for the drug by Nov. 9.
The second anticipated FDA verdict is for Denali Therapeutics’ enzyme replacement therapy tividenofusp alfa. Phase I/II data revealed in February showed the treatment elicited “substantial and significant” improvements in disease biomarkers, while also leading to better hearing and developmental outcomes.
The biotech in April launched a rolling Biologics License Application for the asset, which it wrapped up a month later. Denali announced Monday that the FDA has set a target action date of Jan 5. 2026, pushing this potential catalyst just into the new year.
In its note on Sunday, Jefferies analysts said these decisions could give the industry a clearer picture of how the “new” FDA regards drug applications, particularly for rare diseases and gene therapies. “There is still uncertainty on new FDA [especially] on the rare disease side,” Jefferies wrote.
There have been some positive signals, however. FDA chief Marty Makary in April, for one, said he was open to considering expedited reviews for rare disease applications, while Vinay Prasad, head of the Center for Biologics Evaluation and Research (CBER), has said that his office will “rapidly make available” therapies for rare diseases. “We hope to see this play out and are looking for important FDA approvals,” including for these two applications in Hunter syndrome, Jefferies wrote.
Atai Approaches Phase IIB Schizophrenia Readout
Following an encouraging showing in treatment-resistant depression, atai Life Sciences is now looking ahead to a Phase IIb readout for its neuromodulator RL-007, which the Berlin-based biotech is studying as a treatment for patients with cognitive impairment associated with schizophrenia (CIAS).
According to a corporate presentation, the data drop for RL-007 is expected in the third quarter of 2025.
Impaired cognition is a “core feature” of schizophrenia, according to atai’s presentation, noting that around 18 million people worldwide suffer from this condition. There are currently no available treatments for CIAS.
Designed to be taken orally, RL-007 is a neuromodulator that in earlier studies has shown reproducible benefits to patient cognition. Phase IIa data, for instance, showed dose-related improvements in cognitive function as measured by a standard testing metric. Electroencephalogram findings also demonstrated improvements in markers of alertness.
Atai has so far investigated RL-007 in more than 500 patients, painting a favorable picture of its safety and tolerability. The biotech has so far detected no drug-related serious adverse events alongside a “minimal” potential for drug-drug interactions, as per its presentation. This profile positions RL-007 as a potential add-on therapy to current standard of care in schizophrenia.
Last week, Beckley Psytech —with whom atai is expected to merge—reported that the intranasal psychedelic BPL-003 significantly lowers depressive symptoms in patients with treatment-resistant depression. BPL-003’s data are part of predetermined “success criteria” in order for the merger to proceed.
Nektar Builds Rezpeg Profile With Alopecia Areata Data
Last on this list is Nektar Therapeutics, which is awaiting a Phase IIb readout for its T cell stimulator rezpegaldesleukin, also known as rezpeg. The biotech expects data in the fourth quarter.
Rezpeg works by binding to the IL-2 receptor, in turn triggering the proliferation of regulatory T cells, while also avoiding the activation of cytotoxic CD8+ and CD4+ T cells, both of which are known to drive autoimmune conditions.
San Francisco–based Nektar is proposing the use of rezpeg for various immune-mediated and inflammation-driven diseases. In February this year, the company announced that it hit its enrollment target for the Phase IIb REZOLVE-AA study, which will test the biologic in patients with severe to very severe disease who have not yet been treated with a JAK inhibitor or other biologics. Aside from alopecia areata, Nektar is also testing rezpeg in type 1 diabetes and atopic dermatitis.
Last month, Nektar reported Phase IIb data for rezpeg in atopic dermatitis, with CEO Howard Robin calling its outcomes “compelling.” Analysts seem split on the matter, however. William Blair in a note at the time said rezpeg suffers from “an absence of clear differentiation in the highly competitive atopic dermatitis field.”
In contrast, B. Riley Securities called the mid-stage atopic dermatitis readout “a near home-run” for Nektar, saying they were “most impressed” by rezpeg, which was able to demonstrate “robust stat. sig. placebo-adjusted efficacy on highly stringent, objective key secondary efficacy endpoints.”
