Key upcoming clinical catalysts for biotech

Early 2021 will see rare diseases dominate for biotech, with Sarepta revealing key data on its gene therapy play.

An earlier analysis by Evaluate Vantage concentrated on upcoming big pharma data reveals; here, we take a look at the clinical results due for biotech companies with a market cap of $2bn and above.

Rare diseases dominate, with the likes of Alnylam and Alexion – soon to become part of Astrazeneca – gearing up for data. Probably the most eagerly awaited readout, though, concerns Sarepta's first placebo-controlled trial of SRP-9001, a micro-dystrophin gene therapy for Duchenne muscular dystrophy.

Roche paid $750m upfront to secure ex-US rights to SRP-9001 at the end of last year. With an NPV of $7.6bn, according to Evaluate Omnium, ’9001 is one of biotech's most valuable pipeline projects, but before its lofty sales expectations can be realised it first needs to perform in the clinic.

The phase II trial, called Study 102, has enrolled 41 boys aged 4-7 with DMD. The primary outcomes are the change in quantity of micro-dystrophin protein expression at week 12 and the change in North Star Ambulatory Assessment (NSAA) total score at week 48. 

So far ’9001 has shown promise – in four patients. In a phase I trial, microdystrophin expression levels were 74-96% of normal at week 12, and there was a mean seven-point improvement on NSAA at two years. In terms of rivals, Sarepta’s project looks more effective that Pfizer’s gene therapy PF-06939926, albeit comparing two different trials involving small numbers of patients.

Three patients taking ’9001 experienced elevated γ-glutamyl transpeptidase, a liver enzyme, in the first three months post-treatment, which resolved with steroids. Despite this, the safety profile of Sarepta’s project looks cleaner than those of rival gene therapies.

Three serious events occurred in Pfizer’s phase Ib trial of PF-06939926, with two said to be due to complement activation; still, these resolved quickly and a phase III study recently started recruiting. A phase I/II study of Solid Biosciences’ SGT-001, meanwhile, was halted due to a series of adverse events, but dosing is expected to resume in the first quarter of next year.

More convenient

Alnylam’s vutrisiran, a subcutaneous follow-on to the group's intravenous amyloidosis therapy Onpattro, is due to report phase III data soon. 164 patients in the Helios-A study, who have hereditary transthyretin amyloidosis with polyneuropathy, are being given vutrisiran once every 12 weeks or Onpattro once every three weeks.

The primary endpoint of the study is change from baseline in the modified neurologic impairment score at nine months. Results from the vutrisiran arm will be compared against the placebo arm of the phase III Apollo-A study, which led to Onpattro’s approval in polyneuropathy patients.

In order to compete with Pfizer’s once daily Vyndaqel tablet, Alnylam needs to show its projects can improve cardiac measures − Vyndaqel is on the market for the cardiomyopathy subtype, a bigger indication. Pfizer’s project is also approved outside the US for polyneuropathy.

In cardiomyopathy patients, Alnylam’s Helios-B study of vutrisiran is still recruiting, and the Apollo-B study of Onpattro is expected to read out in 2022.

Copper target

Alexion's late-stage Wilson disease project, ALXN1840, probably did not feature highly on Astra's wish list when it agreed to pay $39bn for the biotech group, but a win here would be a bonus. 

Alexion gained the project through its $855m takeout of the Swedish company Wilson Therapeutics in 2018.

Wilson disease is an autosomal recessive metabolic disease characterised by copper build-up in the liver or brain, and ALXN1840 is said to work as a copper-protein binding agent. The phase III study in 215 Wilson disease patients is designed to show ALXN1840’s superiority versus copper-chelating agents followed by zinc maintenance. Alexion notes that the current standard of care can be burdensome as it involves multiple tablets and fasting, and does not address the neurological symptoms of the disorder.

The primary endpoint looks at the change from baseline to week 48 in non-ceruloplasmin-bound copper levels. Secondary measures include effects on neurological status and clinical symptoms.

Alexion’s project, however, does not address the underlying genetic mutation causing the disease. A phase I/II study of VTX-801, a gene therapy for Wilson disease, is expected to start early next year. The project is a collaboration between Vivet Therapeutics and Pfizer, which acquired an equity interest in the private gene therapy company in 2019.

Check out the table below for a full list of upcoming catalysts with consensus forecasts from EvaluatePharma. Evaluate Vantage has separately assessed expected catalysts for big pharma.

Q1 clinical catalysts (excludes Covid-19 data)
Project Company  Therapy area Q1 clinical catalyst 2026e indication sales ($m) Note/Vantage coverage
SRP-9001  Sarepta/Roche Duchenne muscular dystrophy Ph2 Study 102 2,901 See text
CTX001 Vertex/Crispr  Beta-thalassaemia, sickle cell disease Updates during 2021 from Climb-Thal-111 and Climb-SCD-121 1,306

Promising early data (Ash 2020 – Crispr gets another boost)

Vutrisiran Alnylam ATTR amyloidosis Ph3 Helios-A early 2021 1,290 See text
Turning Point Therapeutics Solid tumours (harbouring ALK, ROS1, or NTRK1-3 rearrangements) Trident-1 at IASCLC World conference on lung cancer on January 31 1,087 Initial data showed competitive response rates vs Roche's Rozlytrek and Pfizer's Xalkori but need to see evidence of greater durability (Turning Point on the straight track, but to where?)
Zuranolone      (Sage-217)

Sage Therapeutics/ Biogen

Major depression, postpartum depression Four ph3 studies due to report in 2021 970 Biogen paid $1.5bn for rights to zuranolone and Sage-324 (Biogen’s Sage advice amounts to $1.5bn
(valoctocogene roxaparvovec)
Biomarin Haemophilia A Ph3 52-week data from 301 937 EMA requested 1yr data for approval, FDA asked for 2yr data after giving a CRL in August 2020
AT-GAA Amicus Pompe disease Ph3 Propel Q1 637 Sanofi's NeoGAA demonstrated non-inferiority to SoC (Myozyme) but failed to show superiority in ph3; Amicus's Propel study is powered to demonstrate superiority over SoC (Leerink)
Mitapivat Agios PK deficiency Pivotal data (Activate-T) 591 Activate study in patients not receiving regular blood transfusions met its primary endpoint; Activate-T is in more severely affected PKD patients who regularly receive blood transfusions (Agios gets a pre-Ash boost)
APL-2 (systemic pegcetacoplan) Apellis PNH Ph3 Prince H1 554 Treatment naïve study, Pdufa in May for patients who had been on Soliris
IMVT-1401 Immunovant Warm autoimmune haemolytic anaemia, thyroid eye disease Data from ph2a Ascend Waiha due Q1, ph2b Ascend Go-2 due H1 357 Subcutaneous anti-FcRn MAb (Ph3 myasthenia gravis trial to start H1 2021)
ALXN1840 Alexion (now Astrazeneca) Wilson disease Ph3 due H1 322 See text
Bempegaldesleukin + Keytruda
Nektar NSCLC Ph1/2 Propel 228 Preliminary ORR data from ph2 Propel study (~30 patients)
Relugolix Myovant Endometriosis One-year efficacy and safety data from Spirit Extension 167 Keep an eye out for data on thromboembolic events, which could affect the label (Leerink)
Rozanolixizumab  UCB Chronic inflammatory
demyelinating polyneuropathy
Ph2 H1 123 Subcutaneous anti-FcRn MAb, ph3 in myasthenia gravis not due until Q1 2022
Troriluzole Biohaven Mild-to-moderate Alzheimer's disease Ph2/3 T2 Protect AD 114

(Alzheimer’s catalysts round off a year dominated by Biogen)

Relacorilant +
Corcept Ovarian cancer, pancreatic cancer Ph2 ovarian, Ph3 Reliant pancreatic H1 100 Second-generation Korlym, generic Korlym from Teva likely Q1
VX-864 Vertex Alpha-1 antitrypsin deficiency Ph2 H1 - Z-AAT corrector said to be structurally distinct from VX-814 that saw elevated liver enzymes in ph2 and has been discontinued (Clinical setback lays bare Vertex’s weakness)
(cusatuzumab) + Vidaza
Argenx/Johnson & Johnson Newly diagnosed AML unfit for intensive chemo Ph2 top-line Culminate early 2021 - Anti-CD70 MAb, deal with J&J's Cilag division, impressive response rates in earlier study (Argenx keeps delivering)
Camidanlumab tesirine
(Cami, ADCT-301) 
ADC Therapeutics Relapsed or refractory Hodgkin lymphoma Pivotal ph2 interim H1 - Trial resumed in June 2020 after its clinical hold was lifted, two patients had been diagnosed with Guillain–Barré syndrome
Sources: EvaluatePharma, company releases, analyst notes,

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