Go or no go? Mirati heads to the FDA

TG Therapeutics and Gilead also await a verdict, and Cytokinetics is set for a panel.

With the end of 2022 in sight, several important FDA approval decisions are still on the cards, including an accelerated verdict on Mirati’s adagrasib. A green light would set the Kras inhibitor up for a battle against Amgen’s rival drug Lumakras, so any differences in labels will be key.  

Elsewhere, TG Therapeutics will be hoping to forget its troubled oncology past with an approval for ublituximab in multiple sclerosis, but a crowded market awaits. Also, while Gilead’s long-acting lenacapavir looks set for a thumbs-up in heavily pretreated HIV patients, a bigger commercial opportunity lies in earlier lines of therapy.  

The only panel meeting next month is for Cytokinetics’ novel myosin activator omecamtiv, but a lacklustre data hit driven by a subgroup could mean that the project will get a grilling by the US regulator.  

Kras battle  

The regulatory battle between Amgen and Mirati’s Kras inhibitors will reach a head next month with an accelerated approval decision for Mirati’s adagrasib. The filing was based on the phase 2 Krystal-1 study, which produced efficacy data in line with Amgen’s Codebreak 100 trial on which Lumakras gained an accelerated approval in 2021.  

Analysts expect a green light and note that differentiation between adagrasib and Lumakras’s labels will be key, with a focus on hepatotoxicity rates. Lumakras’s label includes dose-modification instructions in the event of grade 3/4 liver enzyme elevations, or grade 2 with symptoms. Elevations were evident in Krystal-1, but not to the same extent as those seen in Codebreak 100.  

Securing a full approval is still some way off for Mirati; its confirmatory Krystal-12 study is recruiting and has a primary completion date next August. Lumakras has confirmatory Codebreak 200 data in the bag already but efficacy disappointed and there were incidences of drug-induced liver injury. The data have not yet been filed with the FDA.   

TG’s redemption?  

After a three-month delay, TG Therapeutics will see the FDA rule on ublituximab before the year is out. The anti-CD20 MAb is intended to treat relapsing forms of multiple sclerosis.  

The company stated on its recent third-quarter call that labelling discussions had started, which investors took as a sign that approval is likely, and shares rallied on the news.   

The MS market is crowded with big pharma players and ublituximab will need to differentiate itself. On a cross-trial basis TG’s therapy looks competitive with other anti-CD20 MAbs. In ublituximab’s Ultimate 1 and 2 studies the annual relapse rates (ARR) were under 0.1. The rates for Roche’s Ocrevus’s and Novartis’s Kesimpta in phase 3 came in at 0.16 and around 0.11 respectively.  

Ublituximab also has convenience on its side: it is dosed less frequently than subcutaneous Kesimpta, and has a shorter infusion time than Ocrevus, though a subcutaneous version of Ocrevus is in phase 3.  

According to consensus forecasts from Evaluate Pharma Ocrevus is set to be the market leader in relapsing MS in 2028 with sales of $6.5bn, and Kesimpta is expected to take second place. Ublituximab forecasts sit at a mere $842m.   

An approval will help TG shake off its previous regulatory troubles; the group’s cancer drug Ukoniq was withdrawn earlier this year due to safety issues.  

Sunlenca’s US turn  

Gilead’s long-acting capsid inhibitor lenacapavir is approved in Europe as Sunlenca and its turn in the US is expected before the year is out. An earlier issue with the therapy’s vials led to an FDA knockback in March, with new containers now in use.  

Initially, Gilead is going after heavily treatment-experienced patients with multi-drug resistant HIV, based on positive data from the phase 2/3 Capella trial. Consensus forecasts for the project are lofty, with 2028 sales of $1.6bn, and a move into earlier lines of therapy should help achieve these. Monotherapy studies in pre-exposure prophylaxis are ongoing, as are a number of combination trials.   

Rocky road ahead  

The last FDA adcom of the year will concern Cytokinetics’ omecamtiv, a myosin activator. However, several factors, including underwhelming clinical data, mean the meeting will be far from plain sailing for the company.  

The pivotal Galactic-HF trial hit its primary endpoint, a composite of death or heart failure events, but showed an underwhelming result. And a key secondary measure, cardiovascular death, was missed. A post-hoc analysis determined that a subgroup of patients, those with severe heart failure, were driving the hit. The FDA looks likely to limit the drug's use to more severe patients, but might request another study.  

The tables below list first-time and supplementary US approval decisions, as well as advisory committee meetings, due next month, with consensus forecasts from Evaluate Pharma

Notable first-time US approval decisions due in December
Project Company Pdufa date Indication(s) 2028e SBI ($m) Note
Adagrasib Mirati Dec 14 (accelerated) 2L Kras G12C-mutated NSCLC 1,313 See text
Tuoyi (toripalimab) Coherus Dec 23 (resubmitted) Nasopharyngeal carcinoma - Previous CRL due to quality process change
Sunlenca (lenacapavir)  Gilead Dec 27 (resubmitted) HIV-1 infection in heavily treatment-experienced people with multi-drug resistant HIV-1 infection  1,602 Previous CRL for vial CMC issues, see text
Ublituximab TG Therapeutics Dec 28 Relapsing MS 842 See text
Lunsumio (mosunetuzumab) Roche/Biogen Dec 29 3L follicular lymphoma - CD20xCD3 T-cell engaging bispecific, approved in Europe
Sohonos (palovarotene) Ipsen Dec 29 (resubmitted, likely delayed) Fibrodysplasia ossificans progressiva 152 Adcom in Oct was delayed by FDA request for info on clinical trial data, no new dates for the adcom or Pdufa have been disclosed
Nexobrid Mediwound/Vericel Jan 1 (resubmitted) Eschar removal (debridement) in adults with deep partial-thickness and/or full-thickness thermal burns 78 Could come by end of the Dec, previous CRL due to CMC
Tislelizumab Beigene/Novartis Decision deferred pending manufacturing inspections 2L oesophageal squamous cell carcinoma 83 Original Pdufa Jul 12, 2022
Annik/Anniko (penpulimab) Akeso/Sino No news 3L nasopharyngeal carcinoma - Approval had been expected H1
Rebyota (RBX2660) Ferring (private) Before YE? Reduce the recurrence of Clostridioides difficile infection in adults following antibiotic treatment for recurrent C diff infection - Favourable adcom in Sep, Pdufa date undisclosed
SBI: sales by indication. Source: Evaluate Pharma, company releases.


Advisory committee meetings due in December
Project Company Adcom date Indication 2028e SBI ($m) Note
Omecamtiv Cytokinetics Dec 13 Reduce the risk of CV death and heart failure events in patients with symptomatic chronic HFrEF 326 Novel myosin activator, Ph3 Galactic-HF study disappointed (Cytokinetics aims to become the Vertex of cardiovascular disease)
HFrEF:  heart failure with reduced ejection fraction. Source: Evaluate Pharma, company releases, FDA adcom calendar.


Supplementary and other notable approval decisions due in December
Product Company Indication (clinical trial) Date
Vraylar Abbvie Adjunctive treatment of major depressive disorder (NCT03738215) Est Dec 22
Tymlos (abaloparatide) Radius Men with osteoporosis at high risk for fracture (Atom) Dec 25
Abrilada (Humira biosimilar) Pfizer Interchangeability designation Q4
Lynparza + Zytiga + prednisone/prednisolone Astrazeneca Metastatic castration-resistant prostate cancer (Propel) Q4
Source: Evaluate Pharma, company releases.

Share This Article