Abecma competition, Sotyktu pricing pressure and IRA: Analysts outline Bristol Myers’ top challenges

2024-07-12

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来源: FiercePharma

Several of Bristol Myers' top growth drivers face current and future challenges, according to the team at Leerink Partners.

Several challenges across Bristol Myers Squibb’s business have Leerink Partners analysts worried about the future—despite a few promising growth opportunities the team has identified.

A Leerink team led by David Risinger has lowered its revenue forecast for several important BMS growth products from 2025 and beyond. The TYK2 anti-inflammation drug Sotyktu, the S1P receptor modulator Zeposia, the multiple myeloma CAR-T Abecma, the immunotherapy fixed combo Opdualag, and the newly acquired antipsychotic candidate KarXT each face their own challenges, the team said.

In addition, industry watchers will have a better idea on the price-reduction impact of the Inflation Reduction Act for BMS’ Pfizer-partnered megablockbuster blood thinner Eliquis later this year.

With Revlimid losing market exclusivity and Opdivo facing patent expirations later this decade, BMS is fully aware it’s heading into a transition period. But it has been counting on its newer meds to drive “top-tier” growth from late 2020s, executives have said.

For Sotyktu, a first-in-class pill that’s approved for plaque psoriasis, the Leerink analysts flagged “severe payer access restrictions,” as well as potential launches of rival oral agents in 2027 and beyond. Under continued pricing pressure, BMS anticipates only 10% sequential revenue growth for Sotyktu in the second quarter of this year, a relatively modest figure for a new launch.

“As we see it, the company effectively has to give Sotyktu away (for just the copay card $ amount it receives from patients) until it can generate enough volume to justify being covered by formularies,” the Leerink team said in a Friday note.

BMS doesn’t have much time to make it worthwhile for payers. Johnson & Johnson is running the phase 3 ICONIC-ADVANCE 2 trial pitting its novel oral IL-23R antagonist, JNJ-2113, against Sotyktu in plaque psoriasis. The trial bears a primary completion date in February 2025.

BMS has labeled Sotyktu as a “key growth driver to establish leadership in immunology.” The drug is looking at a potential phase 3 readout this year in psoriatic arthritis, plus other expansion opportunities in autoimmune diseases such as lupus and Sjogren’s syndrome down the line.

But Leerink has now pegged Sotyku to reach estimated 2030 sales of just $832 million, way below the $1.9 billion Wall Street consensus. BMS’ own projection? More than $4 billion in peak sales.

Also in BMS’ immunology franchise, a phase 3 failure in Crohn’s disease was a clear blow to Zeposia, especially as AbbVie’s oral JAK inhibitor Rinvoq JAK inhibitor Rinvoq and injectable Skyrizi each chalked up wins in the inflammatory bowel disease subtype.

In Leerink’s updated calculation, Zeposia is expected to reach worldwide sales of $805 million in 2030. BMS, for its part, has estimated the drug could bring in $3 billion by that time.

One possible bright spot in BMS’ immunology franchise comes in the form of a CAR-T program, CD19 NEX-T, for lupus. Recent anecdotal reports of remarkable results in serious lupus cases have triggered enthusiasm for using CAR-T cells to eliminate autoreactive B cells behind the disease—perhaps for good. But a case of fast relapse despite initial response from Kyverna Therapeutics’ CAR-T candidate in lupus nephritis has cast a shadow over the strategy.

BMS is expected to report phase 1 data for NEX-T later this year, the Leerink team noted.

Speaking of CAR-T, BMS has been struggling with its anti-BCMA therapy Abecma because of tough competition from Johnson & Johnson and Legend Biotech’s Carvykti. With a recent FDA approval, Carvykti has jumped into the second-line treatment setting, whereas Abecma has only reached the third line. In addition, Carvykti’s new overall survival win will likely put it even further ahead of Abecma in doctors’ minds.

During an investor call in March, Legend execs noted that Carvykti was holding about 80% of market share at treatment centers that offer both BCMA CAR-Ts. Legend execs said the company was looking to snatch the remaining share by increasing supply, arguing that BMS’ Abecma was only able to secure its own share thanks to Carvykti’s production bottleneck.

Leerink now projects Abecma sales of just $556 million in 2030. Both Wall Street consensus and Bristol’s own target have put the number at above $1 billion.

Prospects are not that sunny elsewhere on BMS’ home turf of oncology. Specifically, the PD-1/LAG-3 combo Opdualag may “face serious competition” from Regeneron’s LAG-3 candidate fianlimab, the Leerink team pointed out. Fianlimab’s phase 3 data in first-line melanoma are expected in 2025, and Regeneron has been bullish that its data will look better than Opdualag in a cross-trial comparison, the Leerink analysts said.

The more important indication for the checkpoint inhibitor class is lung cancer. There, BMS’ chief medical officer, Samit Hirawat, M.D., recently told Leerink analysts that Opdualag has shown positive phase 2 data in an undisclosed subset of non-small cell lung cancer patients, who represent about 20% to 30% of the patient population. A phase 3 trial in that subgroup is being planned for the second half of this year.

BMS’ plan was to advance the combination of Opdualag and chemotherapy and compare it against Keytruda and chemo. But the company would need to discuss the control arm comparator with the FDA given the evolving treatment landscape, the Leerink team said in a note in March. Should a newer treatment regimen be included for comparison, BMS may have to face a higher efficacy bar than it had encountered in the phase 2, the Leerink analysts said.

Elsewhere, BMS recently acquired Karuna and its close-to-market schizophrenia candidate KarXT in a $14 billion deal. The New Jersey pharma has touted the drug’s “multibillion-dollar” peak sales potential if future clinical studies pan out.

With an FDA target date in September, BMS plans to launch the first-in-class M1/M4-preferring muscarinic agonist this year. But Leerink learned that BMS’ filing in Europe has to wait for data readouts from head-to-head trials against generic drugs because EU government payers will only cover KarXT if it shows superior benefit to readily available meds.

As a result, Leerink has lowered KarXT’s ex-U.S. sales estimates. Still, the team’s global 2030 sales projection for KarXT in schizophrenia, at $3.6 billion, is above the consensus figure of $3.1 billion. In Alzheimer’s disease psychosis, Leerink expects potential sales of $916 million, compared with $843 million for consensus.

BMS faces all these challenges while dealing with mandated price adjustments for Eliquis as one of the first 10 drugs selected for Medicare price negotiations under the IRA. The U.S. government will publish the maximum prices negotiated for those drugs by September 1, and BMS will provide guidance on the impact on Eliquis after that. The prices will go into effect in 2026.